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Yuan PQ, Li T, Mahurkar-Joshi S, Sohn J, Chang L, Taché Y. Three-dimensional imaging and computational quantitation as a novel approach to assess nerve fibers, enteric glial cells, mast cells, and the proximity of mast cells to the nerve fibers in human sigmoid mucosal biopsies from healthy subjects. J Neurosci Methods 2025; 418:110436. [PMID: 40180160 DOI: 10.1016/j.jneumeth.2025.110436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 03/14/2025] [Accepted: 03/24/2025] [Indexed: 04/05/2025]
Abstract
BACKGROUND The visualization and quantitation of nerve fibers (NFs), enteric glial cells (EGCs), mast cells (MCs), and their spatial configurations in the human colonic mucosa represent considerable challenges due to the meshed network of these components and the arborizing of NFs in a three-dimensional (3D) structure. NEW METHOD We developed a novel approach combining tissue clearing, 3D imaging and computerized quantitation of NFs, EGCs and MCs in sigmoid mucosal biopsies of healthy subjects using a modified CLARITY tissue clearing protocol and adapting Imaris Surfaces Rendering Technology. RESULTS The cleared colonic biopsies are compatible with immunostaining using 10 marker antibodies and capable of generating 3D images rendering clear spatial views and computational quantitation of NFs, MCs, EGCs, in particular the proximity of MCs to NFs with Imaris 9.7-9.9. COMPARISON WITH EXISTING METHODS Our modified tissue clearing protocol shortened the membrane lipid removal time to 1 day from the original 1-2 weeks and total tissue clearing time to 3-4 days from the original 2-4 weeks. The 3D images displayed a clear spatial landscape of NFs, MCs and EGCs in the biopsies which cannot be portrayed with 2D images acquired from sections. Computerized quantitation is faster than measuring manually, allowing us to quantify a larger number of samples with less bias. CONCLUSION The novel approach enables faster tissue clearing/immunolabeling, high-quality 3D imaging and precise computational quantitation of NFs, cells and proximity of MCs to NFs in human sigmoid biopsies which may allow new insight to detect alterations in colonic-related diseases.
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Affiliation(s)
- Pu-Qing Yuan
- Digestive Diseases Research Center, Vatche and Tamar Manoukian Digestive Diseases Division, David Geffen School of Medicine, UCLA, USA; VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
| | - Tao Li
- Digestive Diseases Research Center, Vatche and Tamar Manoukian Digestive Diseases Division, David Geffen School of Medicine, UCLA, USA
| | - Swapna Mahurkar-Joshi
- Digestive Diseases Research Center, Vatche and Tamar Manoukian Digestive Diseases Division, David Geffen School of Medicine, UCLA, USA; G Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Digestive Diseases Division, David Geffen School of Medicine, UCLA, USA
| | - Jessica Sohn
- Digestive Diseases Research Center, Vatche and Tamar Manoukian Digestive Diseases Division, David Geffen School of Medicine, UCLA, USA; G Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Digestive Diseases Division, David Geffen School of Medicine, UCLA, USA
| | - Lin Chang
- Digestive Diseases Research Center, Vatche and Tamar Manoukian Digestive Diseases Division, David Geffen School of Medicine, UCLA, USA; G Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Digestive Diseases Division, David Geffen School of Medicine, UCLA, USA
| | - Yvette Taché
- Digestive Diseases Research Center, Vatche and Tamar Manoukian Digestive Diseases Division, David Geffen School of Medicine, UCLA, USA; G Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Digestive Diseases Division, David Geffen School of Medicine, UCLA, USA; VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
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Yıldız G, Söğüt G. Masked hypertension in patients with irritable bowel syndrome. Indian J Gastroenterol 2025:10.1007/s12664-025-01745-z. [PMID: 40126783 DOI: 10.1007/s12664-025-01745-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 01/15/2025] [Indexed: 03/26/2025]
Abstract
BACKGROUND The pathophysiology of irritable bowel syndrome (IBS) and masked hypertension (mHT) exhibits shared characteristics, including factors such as anxiety and stress. Consequently, the aim of this study was to investigate the frequency of mHT in patients with IBS. METHOD Patients diagnosed with IBS in 2020-2023 were re-evaluated using the Rome IV criteria. Patients who did not have sustained HT, as evidenced by repeated in-office blood pressure (BP) measurements and who did not meet the exclusion criteria (chronic renal failure, heart failure, diabetes, cerebrovascular events, pregnancy or puerperium) were included in the study group. A control group was also constituted with the same number of age and gender-matched healthy individuals. The participants were connected to a 24-hour ambulatory BP monitor and the results were analyzed. RESULTS Total 128 participants, including 64 IBS patients and 64 healthy individuals, were included in our study. The age (36.9 ± 7.3 years; 37.3 ± 7.7 years) and gender (62.5% female; 62.5% female) distributions and the baseline clinical characteristics of the study and control groups were similar. The in-office systolic BP measurements of the IBS patients were significantly higher than those of the control group (124.7 ± 5.4 mmHg compared to 121.8 ± 5.2 mmHg, p = 0.02). The IBS patients also had a higher frequency of mHT (n = 21, 32.8% compared to n = 10, 15.6%, p = 0.02), higher 24-hour daytime systolic BP (127.5 ± 7.6 mmHg compared to 124.8 ± 5.22 mmHg, p = 0.02) and higher nighttime diastolic BP (62.2 ± 7.5 mmHg compared to 59.6 ± 6.1 mmHg, p = 0.03) than the control group. The study group included all four sub-types of IBS: diarrhea-dominant (IBS-D), constipation-dominant (IBS-C), mixed type (IBS-M) and unclassified (IBS-U). It was determined that 57.9% of the IBS-C patients, 27.8% of the IBS-M patients, 23.5% of the IBS-D patients and 10% of the IBS-U patients in the study group had mHT. CONCLUSION To the best of our knowledge, this is the first study demonstrating a relationship between IBS and mHT. The frequency of mHT was higher among patients with IBS compared to healthy controls (p = 0.02). Studies on larger patient groups are needed to evaluate the frequency of mHT for the IBS sub-types.
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Affiliation(s)
- Görkem Yıldız
- Cardiology Department, Yüksek İhtisas University, Balgat, Ankara, Türkiye.
| | - Gürbey Söğüt
- Cardiology Department, Ankara Etlik State Hospital, Etlik, Ankara, Türkiye
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Qiao C, Qin X, Song Y, Guan R, Li B, Zuo Y, Wei W, Han T, Jiang W. Association of childhood emotional neglect, circulating protein biomarkers, with gastrointestinal disorders among UK biobank participants. J Affect Disord 2025; 380:317-330. [PMID: 40120955 DOI: 10.1016/j.jad.2025.03.114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 03/16/2025] [Accepted: 03/19/2025] [Indexed: 03/25/2025]
Abstract
OBJECTIVE To explore the association between CEN and GIDs, and elucidated the potential role of circulating protein biomarkers. PATIENTS AND METHODS The study utilized UK Biobank data from 156,686 participants, with data collection occurring between March 13, 2006 and October 1, 2010. Participants with GIDs at baseline were excluded from further analysis. CEN data were obtained from the baseline assessments. Differential protein analyses were conducted using OLINK data. GIDs and their subclasses were identified through electronic health records. Cox proportional hazards regression models were employed to assess the association between CEN and the risk of GIDs, along with sensitivity and multidimensional stratification analyses. Additionally, mediation analysis was performed to explore the role of differential protein biomarkers. RESULTS The results indicated that the mild CEN (CENmild) group was associated with a significantly lower risk of various GIDs than the severe CEN (CENsevere) group, including overall GIDs (HR = 0.78,95%CI:0.74-0.81) and peptic ulcers (HR = 0.37,95%CI:0.20-0.68). OLINK differential analysis revealed that APOF expression was significantly higher in the CENmild group compared to the CENsevere group (PAPOF = 7.09E-08,FC = 0.048), whereas other differential protein expression (PBPIFB2 = 8.93E-06,FC = -0.122;PFABP4 = 3.19E-06,FC = -0.101;PGGH = 4.58E-07,FC = -0.054;PLEP = 5.39E-08,FC = -0.195) was significantly lower in the CENsevere group. Cox regression analysis showed that higher APOF expression was associated with a reduced risk of multiple GIDs, while the expression of other differential proteins increased the risk of corresponding GIDs. Mediation analysis indicated that these proteins mediated 0.5 % to 6.7 % of the CEN-GIDs association. CONCLUSION In this cohort study, CEN was significantly associated with a higher risk of GIDs in the adulthood, and circulating protein biomarkers partially mediated the associations.
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Affiliation(s)
- Conghui Qiao
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, PR China
| | - Xiaowen Qin
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, PR China
| | - Yuqing Song
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, PR China
| | - Ruijie Guan
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, PR China
| | - Bai Li
- Department of Biology, University of Ottawa, 30 Marie-Curie Private, Gendron Hall, Ottawa, ON K1N 9B4, Canada
| | - Yingdong Zuo
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, PR China
| | - Wei Wei
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, PR China.
| | - Tianshu Han
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, PR China.
| | - Wenbo Jiang
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, PR China; Department of Biology, University of Ottawa, 30 Marie-Curie Private, Gendron Hall, Ottawa, ON K1N 9B4, Canada.
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Meshkat S, Lin Q, Tassone VK, Janssen-Aguilar R, Ym Pang H, Lou W, Bhat V. Acid reflux medication use among adults with depressive symptoms. J Affect Disord 2025; 379:747-754. [PMID: 40090389 DOI: 10.1016/j.jad.2025.03.085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 03/11/2025] [Accepted: 03/13/2025] [Indexed: 03/18/2025]
Abstract
Emotional stress, including depression, may contribute to increased gastroesophageal reflux disease symptoms. In this paper, we aim to evaluate the associations between depressive symptoms, depressive symptom severity, and symptom clusters with acid reflux medication use, considering the potential interaction effect of sex. Data from the 2007-2018 National Health and Nutrition Examination Survey were used. Participants aged 18 years or older were included if they responded to the depressive symptoms and prescription medication questionnaires. This study included 31,444 participants, of whom 2871 had depressive symptoms. Participants with depressive symptoms had significantly higher odds of using antacids (aOR = 1.735; p < 0.001), histamine-2 receptor antagonists (H2RAs) (aOR = 1.653; p < 0.001), and proton pump inhibitors (PPIs) (aOR = 1.723; p < 0.001). A positive association was also found between depressive symptom severity and the use of antacids (aOR = 1.054; p < 0.001), H2RAs (aOR = 1.048; p < 0.001), and PPIs (aOR = 1.053; p < 0.001). Moreover, increases in cognitive-affective and somatic scores were associated with higher odds of using antacids (aOR = 1.080 for cognitive, 1.102 for somatic; p < 0.001), H2RAs (aOR = 1.078 for cognitive, 1.083 for somatic; p < 0.001), and PPIs (aOR = 1.075 for cognitive, 1.105 for somatic; p < 0.001). No significant sex interaction effects were observed. Adjusted models demonstrated no significant associations between depressive symptoms and the duration of medication use. This study provides evidence of an association between depressive symptoms and acid reflux medication use, highlighting the need to screen for related symptoms in patients with depressive symptoms.
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Affiliation(s)
- Shakila Meshkat
- Interventional Psychiatry Program, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
| | - Qiaowei Lin
- Interventional Psychiatry Program, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada; Department of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Vanessa K Tassone
- Interventional Psychiatry Program, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada; Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Reinhard Janssen-Aguilar
- Interventional Psychiatry Program, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada
| | - Hilary Ym Pang
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
| | - Wendy Lou
- Department of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Venkat Bhat
- Interventional Psychiatry Program, St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada; Neuroscience Research Program, St. Michael's Hospital, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
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Jeong ES, Jung HK, Choi E, Yun K, Lee A, Kim YS. Characterization of post-inflammatory irritable bowel syndrome animal model following acute colitis recovery. Sci Rep 2025; 15:8512. [PMID: 40075091 PMCID: PMC11904205 DOI: 10.1038/s41598-025-88981-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 02/03/2025] [Indexed: 03/14/2025] Open
Abstract
Irritable bowel syndrome (IBS) is a prevalent disorder with an unclear pathophysiology. This study aimed to investigate the features of dextran sulfate sodium (DSS)-induced low-grade inflammation using murine models of acute severe colitis (acute model) and chronic mild repeated colitis (chronic model), with potential implications for IBS research. The acute model was induced with 3% DSS for 5 days, followed by a 12-week recovery period. The chronic model involved administration of 0.5% DSS for 5 days, followed by a 5-day resting period, repeated thrice. We conducted comparative analyses to assess inflammation severity, intestinal motility, permeability, visceral hypersensitivity, and microbiome composition. In the acute model, mild leukocyte infiltration was observed, colonic transit time shortened at 12 weeks (P < 0.001), occludin expression decreased (P = 0.041), inflammatory cytokines, and transient receptor potential vanilloid 1 was upregulated in colonic mucosa (P < 0.050). In the chronic model, only mild inflammatory changes were noted. Microbiota analysis in the acute model revealed differences in microbial abundance and compositions (P = 0.001). The acute model demonstrated low-grade inflammation that caused gut dysmotility, altered permeability, and increased visceral hypersensitivity with notable microbial composition changes, potentially relevant to IBS phenotypes.
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Affiliation(s)
- Eui Sun Jeong
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - Hye-Kyung Jung
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea.
| | - Euno Choi
- Department of Pathology, College of Medicine, Ewha Womans University, Seoul, Korea
| | | | - Ayoung Lee
- Department of Internal Medicine, College of Medicine, Korea University, Ansan, Gyeonggi-do, Korea
| | - Yong Sung Kim
- Digestive Disease Research Institute, College of Medicine, Wonkwang University, Iksan, Jeonlabuk-do, Korea
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Shen MY, Lou QY, Liu S, Li ZJ, Lin TC, Zhou R, Feng DD, Yang DD, Wu JN. The efficacy and safety of auricular acupoint therapy on treating functional dyspepsia with insomnia: study protocol for a randomized controlled trial. Front Med (Lausanne) 2025; 12:1496502. [PMID: 40144883 PMCID: PMC11937052 DOI: 10.3389/fmed.2025.1496502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 02/28/2025] [Indexed: 03/28/2025] Open
Abstract
Background Functional dyspepsia (FD) is a prevalent health issue currently lacking optimal treatment options, with its global incidence rate increasing in recent years. Clinical studies have recently focused on the application of auriculotherapy in functional gastrointestinal disorders that are accompanied by negative emotions. However, few randomized controlled trials have investigated the use of auriculotherapy for FD patients with insomnia, leaving the therapeutic efficacy and safety largely undefined. This study aims to evaluate the clinical efficacy and safety of auriculotherapy in treating FD patients with insomnia. Methods and analysis This study is a single-center, randomized controlled clinical trial involving 80 patients with FD and insomnia. Using a central randomization system, the subjects are randomly assigned to the auricular acupressure group or the sham auricular acupressure group at a 1:1 ratio, with the auricular acupressure group targeting the concha region and the sham auricular acupressure group targeting the earlobe region. The primary outcome is the response rate at 2 weeks, and the secondary outcomes include the response rate at 8 weeks, sleep data assessed by actigraphy, modified Functional Dyspepsia Symptom Diary, short form-Nepean Dyspepsia Index, Self-rated Anxiety Scale, Self-rated Depression Scale, High Arousal Scale, and Heart Rate Variability. Efficacy results will be evaluated at baseline and at 2 and 8 weeks after treatment. Adverse events will be monitored throughout the study observation period. Discussion The results of this trial are anticipated to validate the efficacy and safety of auriculotherapy in improving symptoms of FD and insomnia, as well as in reducing negative emotional states. Clinical trial registration ClinicalTrials.gov, NCT06466044. Registered 14th May 2024, https://register.clinicaltrials.gov.
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Affiliation(s)
- Meng-Yuan Shen
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China
| | - Qin-Yi Lou
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China
| | - Shan Liu
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China
| | - Ze-Jiong Li
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China
| | - Tian-Chen Lin
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China
| | - Rong Zhou
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China
| | - Dan-Dan Feng
- Department of Intensive Care Unit, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, China
| | - Dong-Dong Yang
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China
| | - Jian-Nong Wu
- Department of Intensive Care Unit, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, China
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Mostafa MEA, Alrasheed T. Improvement of irritable bowel syndrome with glucagon like peptide-1 receptor agonists: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2025; 16:1548346. [PMID: 40134805 PMCID: PMC11932899 DOI: 10.3389/fendo.2025.1548346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 02/10/2025] [Indexed: 03/27/2025] Open
Abstract
Introduction Irritable bowel syndrome (IBS) is a severe gastrointestinal condition with symptoms like pain, bloating, diarrhea, and constipation. Glucagon-like peptide-1 (GLP-1) receptors, expressed in the central nervous system and peripheral tissues, have been found to affect gut motility. GLP-1 and its analog ROSE-010 have been shown to inhibit the migrating motor complex and decrease gastrointestinal motility in IBS patients. Aim This systematic review and meta-analysis aim to assess the efficacy and safety of GLP-1 receptor agonists in providing pain and symptom relief for individuals with IBS. Methods The study conducted extensive searches across various databases, including Cochrane Library, Web of Science, PubMed, Google Scholar, and Science Direct, to identify studies on IBS and related drugs. A search strategy using keywords and medical subject heading terms (MeSH) was developed to ensure inclusivity. Exclusion criteria included non-English language studies, books, conference papers, case reports, in vitro studies, animal studies, and non-original articles. Results The study found that ROSE-010 (100 µg) significantly lowered pain intensity in IBS patients compared to a placebo, with an overall odds ratio of 2.30, 95% CI: 1.53-3.46. ROSE-010 (300 µg) is more effective than a placebo for all irritable bowel syndrome subtypes, with consistent effects across trials. ROSE-010 is linked to a greater incidence of nausea, vomiting, and headache than placebo. Conclusion ROSE-010, a glucagon-like peptide-1 receptor agonist, has been shown to reduce pain in individuals with IBS. However, its higher frequency of nausea, vomiting, and headache suggests the need for close monitoring and individualized treatment plans. Further investigation is needed to understand its impact on different IBS subtypes and long-term effects. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024613545.
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Affiliation(s)
- Mohamed E. A. Mostafa
- Department of Anatomy, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia
| | - Tariq Alrasheed
- Department of Internal Medicine, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia
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Giorgio V, Quatrale G, Mennini M, Piccirillo M, Furio S, Stella G, Ferretti A, Parisi P, Evangelisti M, Felici E, Quitadamo P, Di Nardo G. Bifidobacterium adolescentis PRL2019 in Pediatric Irritable Bowel Syndrome: A Multicentric, Randomized, Double-Blind, Placebo-Controlled Trial. Microorganisms 2025; 13:627. [PMID: 40142519 PMCID: PMC11945947 DOI: 10.3390/microorganisms13030627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 03/04/2025] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
The gut microbiota plays a pivotal role in gastrointestinal inflammation and immune response since changes in microbiota may result in abnormal neurotransmitter expression, inducing changes in gastrointestinal sensory-motor function and leading to symptom onset in irritable bowel syndrome (IBS) patients. The Bifidobacterium adolescentis species has a documented immunomodulatory effect through its ability to produce γ-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the mammalian central nervous system, which is reduced in IBS patients. This is a multicentric, randomized, double-blind, placebo-controlled, parallel-arm trial aimed at evaluating the effectiveness of Bifidobacterium adolescentis PRL2019 in children with IBS. IBS children diagnosed according to Rome IV criteria were enrolled and randomized into two groups to receive one stick containing 20 × 109 colony-forming unit of Bifidobacterium adolescentis PRL2019 (Gabapral, Pontenure, Italy) or an equivalent placebo once a day, in a 1:1 ratio, for 12 weeks. Clinical evaluation of symptoms was performed every four weeks using validated scores. Bowel habit characteristics were assessed using the Bristol Stool Chart (BSC). Seventy-two subjects (mean age 12.2 ± 1.8 years, 30 males) were enrolled and randomized into two groups, each of thirty-six patients. No significant differences were observed between the two groups regarding demographic characteristics, distribution of IBS subtypes, or baseline measures of IBS severity and BSC. The proportion of patients achieving complete remission was significantly higher in the BA Group (19/36; 52.8%) than in the Placebo Group (7/36; 19.4%, p = 0.003, odds ratio [OR] 0.216, 95% confidence interval [CI] 0.075-0.619). Both groups obtained a reduction in Total IBS Symptom Severity Scale (IBS SSS), Pain Intensity Score (PIS), Pain Frequency Score (PFS), and Life Interference Score (LIS) from T0 to T12. However, upon intergroup comparison, only in the BA group did the IBS-SSS (p = 0.001), PIS (p = 0.001), LIS (p = 0.015), and PFS (p = 0.005) significantly improve between T0 and T12. BSC showed a greater representation of normal stools (type 3-4) at the end of treatment in the BA group compared with baseline (25% vs. 58.3%, p = 0.004), especially in patients who presented an IBS-constipation subtype at T0 (44.5% vs. 19.4%, p = 0.02). In our study, Bifidobacterium adolescentis PRL2019 reduces the severity and frequency of symptoms in children with IBS, positively affecting bowel habits in children with the IBS-constipation subtype.
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Affiliation(s)
- Valentina Giorgio
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Catholic University of Sacred Heart, 00168 Rome, Italy
| | - Giovanna Quatrale
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, 00189 Rome, Italy
- Pediatric Unit, Sant’Andrea University Hospital, 00189 Rome, Italy
| | - Maurizio Mennini
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, 00189 Rome, Italy
- Pediatric Unit, Sant’Andrea University Hospital, 00189 Rome, Italy
| | - Marisa Piccirillo
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, 00189 Rome, Italy
- Pediatric Unit, Sant’Andrea University Hospital, 00189 Rome, Italy
| | - Silvia Furio
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, 00189 Rome, Italy
- Pediatric Unit, Sant’Andrea University Hospital, 00189 Rome, Italy
| | - Giuseppe Stella
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Catholic University of Sacred Heart, 00168 Rome, Italy
| | - Alessandro Ferretti
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, 00189 Rome, Italy
- Pediatric Unit, Sant’Andrea University Hospital, 00189 Rome, Italy
| | - Pasquale Parisi
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, 00189 Rome, Italy
- Pediatric Unit, Sant’Andrea University Hospital, 00189 Rome, Italy
| | - Melania Evangelisti
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, 00189 Rome, Italy
- Pediatric Unit, Sant’Andrea University Hospital, 00189 Rome, Italy
| | - Enrico Felici
- Pediatric Unit, Children’s Hospital, Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy
| | - Paolo Quitadamo
- Pediatric Gastroenterology and Hepatology Unit, Santobono-Pausilipon Children’s Hospital, 80122 Naples, Italy
| | - Giovanni Di Nardo
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, 00189 Rome, Italy
- Pediatric Unit, Sant’Andrea University Hospital, 00189 Rome, Italy
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Philip V, Kraimi N, Zhang H, Lu J, Palma GD, Shimbori C, McCoy KD, Hapfelmeier S, Schären OP, Macpherson AJ, Chirdo F, Surette MG, Verdu EF, Liu F, Collins SM, Bercik P. Innate immune system signaling and intestinal dendritic cells migration to the brain underlie behavioral changes after microbial colonization in adult mice. Brain Behav Immun 2025; 127:238-250. [PMID: 40068794 DOI: 10.1016/j.bbi.2025.03.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 02/19/2025] [Accepted: 03/06/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND AND AIMS Accumulating evidence suggests the microbiota is a key factor in Disorders of Gut-Brain Interaction (DGBI), by affecting host immune and neural systems. However, the underlying mechanisms remain elusive due to their complexity and clinical heterogeneity of patients with DGBIs. We aimed to identify neuroimmune pathways that are critical in microbiota-gut-brain communication during de novo gut colonization. METHODS We employed a combination of gnotobiotic and state-of-the-art microbial tools, behavioral analysis, immune and pharmacological approaches. Germ-free wild type, TLR signaling-deficient MyD88-/- Ticam1-/- and lymphocyte-deficient SCID mice were studied before and after colonization with specific pathogen-free microbiota, Altered Schaedler Flora, E. coli or S. typhimurium (permanent or transient colonizers). TLR agonists and antagonists, CCR7 antagonist or immunomodulators were used to study immune pathways. We assessed brain c-Fos, brain-derived neurotrophic factor, and dendritic and glial cells by immunofluorescence, expression of neuroimmune genes by NanoString and performed brain proteomics. RESULTS Bacterial monocolonization, conventionalization or administration of microbial products to germ-free mice altered mouse behavior similarly, acting through Toll-like receptor or nucleotide-binding oligomerization domain signaling. The process required CD11b+CD11c+CD103+ dendritic cell activation and migration into the brain. The change in behavior did not require the continued presence of bacteria and was associated with activation of multiple neuro-immune networks in the gut and the brain. CONCLUSIONS Changes in neural plasticity occur rapidly upon initial gut microbial colonization and involve innate immune signaling to the brain, mediated by CD11b+CD11c+CD103+ dendritic cell migration. The results identify a new target with therapeutic potential for DGBIs developing in context of increased gut and blood-brain barrier permeability.
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Affiliation(s)
- Vivek Philip
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada; Campbell Family Mental Health Research Institute, the Centre for Addiction and Mental Health, Toronto, Canada
| | - Narjis Kraimi
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
| | - Hailong Zhang
- Campbell Family Mental Health Research Institute, the Centre for Addiction and Mental Health, Toronto, Canada
| | - Jun Lu
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
| | - Giada De Palma
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
| | - Chiko Shimbori
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
| | - Kathy D McCoy
- Department of Biomedical Research, University Hospital, Bern, Switzerland; Dept. of Physiology and Pharmacology, Snyder Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | | | - Olivier P Schären
- University of Bern, Institute for Infectious Diseases, Bern, Switzerland
| | | | - Fernando Chirdo
- Instituto de Estudios Inmunologicos y Fisiopatologicos - IIFP (UNLP-CONICET), La Plata, Argentina
| | - Michael G Surette
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
| | - Elena F Verdu
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
| | - Fang Liu
- Campbell Family Mental Health Research Institute, the Centre for Addiction and Mental Health, Toronto, Canada
| | - Stephen M Collins
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
| | - Premysl Bercik
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada.
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10
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Wickramasinghe N, Devanarayana NM. Insight into global burden of gastroesophageal reflux disease: Understanding its reach and impact. World J Gastrointest Pharmacol Ther 2025; 16:97918. [PMID: 40094147 PMCID: PMC11907340 DOI: 10.4292/wjgpt.v16.i1.97918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 10/29/2024] [Accepted: 12/10/2024] [Indexed: 03/03/2025] Open
Abstract
The exact worldwide prevalence of gastroesophageal reflux disease (GERD) remains uncertain, despite its recognition as a common condition. This conundrum arises primarily from the lack of a standardized definition for GERD. The gold standard diagnostic tests for GERD, such as pH impedance testing and endoscopy, are cumbersome and impractical for assessing community prevalence. Consequently, most epidemiological studies rely on symptom-based screening tools. GERD symptoms can be both esophageal and extraesophageal, varying widely among individuals. This variability has led to multiple symptom-based definitions of GERD, with no consensus, resulting in prevalence estimates ranging from 5% to 25% worldwide. Most systematic reviews define GERD as experiencing heartburn and/or regurgitation at least once weekly, yielding a calculated prevalence of 13.98%. In 2017, the global age-standardized prevalence of GERD was estimated at 8819 per 100000 people (95% confidence interval: 7781-9863), a figure that has remained stable from 1990 to 2017. Prevalence increases with age, leading to more years lived with disability. GERD significantly impairs quality of life and can lead to multiple complications. Additionally, it imposes a severe economic burden, with the United States alone estimated to spend around 10 billion dollars annually on diagnosis and treatment. In summary, GERD prevalence varies greatly by region and even within different areas of the same province. Determining the exact prevalence is challenging due to inconsistent diagnostic criteria. However, it is well-documented that GERD poses a significant global burden, affecting the quality of life of individuals and creating a substantial healthcare cost.
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Affiliation(s)
- Nilanka Wickramasinghe
- Department of Physiology, Faculty of Medicine, University of Colombo, Colombo 00800, Western Province, Sri Lanka
| | - Niranga Manjuri Devanarayana
- Department of Physiology, Faculty of Medicine, University of Kelaniya, Ragama 11010, Western Province, Sri Lanka
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11
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Garr K, Odar Stough C, Flannery M, Yacob D, Bali Puri N, Kroon Van Diest A. The Impact of Pediatric Disorders of Gut-Brain Interaction on the Family: The Mediating Role of Child Somatic Symptoms. Neurogastroenterol Motil 2025:e70014. [PMID: 40032810 DOI: 10.1111/nmo.70014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 01/27/2025] [Accepted: 02/10/2025] [Indexed: 03/05/2025]
Abstract
BACKGROUND It is important to identify modifiable factors to reduce the negative impact of pediatric disorders of gut-brain interaction (DGBIs) on the family. The current study examined whether child somatic symptoms and caregiver mental health negatively influenced caregiver and family functioning. METHODS Participants were 84 children (8-17 years old) with DGBI symptoms and their caregivers presenting to a specialty DGBI clinic. Participants completed measures assessing demographics, child somatic symptoms, caregiver anxiety and depressive symptoms, and the impact of the child's illness on the family. Regression analyses examined if child somatic symptoms and caregiver and mental health were associated with family outcomes (i.e., Caregiver Health-Related Quality of Life [HRQoL], Family Functioning, Total Family Impact). Mediation analyses examined if child somatic symptoms mediated the association between caregiver mental health and Total Family Impact. KEY RESULTS Child somatic symptoms (self- and caregiver-report) were negatively related to Caregiver HRQoL, Family Functioning, and Total Family Impact (ps < 0.01). Caregiver anxiety was related to poorer Caregiver HRQoL (p < 0.001) and Total Family Impact (p = 0.01), while caregiver depression was negatively related to Family Functioning (p = 0.01). Self-report of child somatic symptoms partially mediated the association between caregiver anxiety and depressive symptoms and the Total Family Impact. CONCLUSIONS AND INFERENCES Findings indicate that child somatic symptoms are one pathway by which caregiver mental health may amplify the impact of pediatric DGBIs on the family. This highlights the importance of screening for child somatic symptoms and caregiver mental health in pediatric DGBI treatment.
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Affiliation(s)
- Katlyn Garr
- Department of Psychology, University of Cincinnati, Cincinnati, Ohio, USA
| | | | - Meghan Flannery
- Department of Psychiatry and Behavioral Health, Nationwide Children's Hospital, Columbus, Ohio, USA
| | - Desale Yacob
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Nationwide Children's Hospital, Columbus, Ohio, USA
- The Ohio State University College of Medicine, Columbus, Ohio, USA
| | - Neetu Bali Puri
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Nationwide Children's Hospital, Columbus, Ohio, USA
- The Ohio State University College of Medicine, Columbus, Ohio, USA
| | - Ashley Kroon Van Diest
- Department of Psychiatry and Behavioral Health, Nationwide Children's Hospital, Columbus, Ohio, USA
- The Ohio State University College of Medicine, Columbus, Ohio, USA
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12
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Hung KW, Leiman DA, Kaza A, Watson R, Chang L, Maratt JK. AGA Institute Quality Indicator Development for Irritable Bowel Syndrome. Gastroenterology 2025; 168:612-622.e4. [PMID: 39818650 DOI: 10.1053/j.gastro.2024.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 10/29/2024] [Accepted: 11/02/2024] [Indexed: 01/18/2025]
Affiliation(s)
- Kenneth W Hung
- Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut
| | - David A Leiman
- Division of Gastroenterology, Duke University School of Medicine, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina
| | - Archana Kaza
- Division of Gastroenterology and Hepatology, University of New Mexico School of Medicine, Albuquerque, New Mexico
| | - Rabindra Watson
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Lin Chang
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California
| | - Jennifer K Maratt
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana; Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana
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13
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Sandberg-Janzon A, Karling P. Prescription of commonly used drugs in patients with functional bowel disorders. A cross-sectional comparison with the general population. Scand J Gastroenterol 2025; 60:253-261. [PMID: 39862135 DOI: 10.1080/00365521.2025.2458070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 01/13/2025] [Accepted: 01/19/2025] [Indexed: 01/27/2025]
Abstract
OBJECTIVES Comorbidity with other conditions is common in functional bowel disorders. We aimed to investigate the prescription patterns of commonly used drugs in patients with irritable bowel syndrome (IBS) and functional unspecific bowel disorder, compared to the general population. MATERIAL AND METHODS Prescriptions of commonly used drugs in 2022 were compared between patients and the general population from the same age group and region in Sweden. RESULTS Of 526 patients, 317 were followed up in 2022 (219 women and 98 men) and were compared to 51,001 women and 55,571 men in the general population. The median follow-up time from the first visit to 2022 was 8 years (25th-75th percentile 6-11 years). Female patients were significantly more likely than controls to be prescribed PPIs, antibiotics, NSAIDs, paracetamol, opioids, muscle relaxants, antimigraine drugs, antidepressants and asthma medications. Male patients were significantly more likely than controls to be prescribed PPIs, opioids, antidepressants, and asthma medications. In the year prior diagnosis and through 2022, female patients showed a significant decline in the use of PPIs (38% vs.10%; p < 0.001), antibiotics (27.5% vs. 20.1%; p = 0.0426), NSAIDs (23.3% vs.14.6%; p = 0.012), opioids (20.6% vs. 7.5%; p < 0.001), and a significantly increase in the use of asthma medications (15.5% vs. 24.2%; p = 0.0088). Male patients showed a significant decline in the use of PPIs and NSAIDs. CONCLUSION Patients with functional bowel disorders are more likely to be prescribed medications for conditions other than IBS. Over time, there was a decline in the prescriptions of most drugs, except for antidepressants and asthma medications.
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Affiliation(s)
| | - Pontus Karling
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
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14
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Vélez C, Garcia-Fischer I, Paz M, Regassa A, Guerrero-López I, Mendez A, Konkel H, Bar N, Barreto EA, Betancourt J, Burton-Murray H, Staller K, Kuo B. Bilingual Perspectives of Functional Dyspepsia Management in People From Underserved Areas. Clin Transl Gastroenterol 2025; 16:e00817. [PMID: 39803952 PMCID: PMC11932584 DOI: 10.14309/ctg.0000000000000817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 11/10/2024] [Indexed: 02/05/2025] Open
Abstract
INTRODUCTION Disorders of gut-brain interaction, such as functional dyspepsia (FD), are prevalent and challenging conditions. In other gastrointestinal (GI) disorders, individuals from underserved areas (UAs) have difficulty accessing care. Little is known about UA FD patient perspectives of their care, especially in those with limited English proficiency. We aimed to characterize patients' experiences with FD management with the goal of informing future studies targeting disorders of gut-brain interaction management in potentially vulnerable communities residing in UAs. METHODS Participants meeting FD criteria were identified in 2 community health centers affiliated with a large academic medical center in the Northeastern United States. Semistructured interviews were conducted in English and Spanish. Transcripts were reviewed by a bilingual panel of investigators using the constant comparative method of iterative data acquisition. Psychosocial stressors and GI symptom severity were assessed. RESULTS A total of 26 participants were interviewed (12 English-speaking and 14 Spanish-speaking). Broadly, GI symptoms were mild and there was mild-to-moderate psychological distress present. Adverse social determinants of health were highly prevalent. Despite mild symptom severity on objective scales, FD severely affected quality of life and interfered with physical, psychological, and social well-being, including avoidance of certain foods and professional/social situations. Study participants (particularly those with limited English proficiency status) reported difficulty in receiving care. Thematic saturation was achieved. DISCUSSION Even when symptoms were mild, interviewees from UAs reported significant FD-related impairment, along with psychological distress. Education interventions targeting FD-related care in UAs should be designed to improve shared decision making in FD, sensitive to the burden of social determinants of health.
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Affiliation(s)
- Christopher Vélez
- Center for Neurointestinal Health, Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Isabelle Garcia-Fischer
- Center for Neurointestinal Health, Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Mary Paz
- Division of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | | | - Ingrid Guerrero-López
- Center for Neurointestinal Health, Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - April Mendez
- Center for Neurointestinal Health, Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Hannah Konkel
- Center for Neurointestinal Health, Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Nir Bar
- Center for Neurointestinal Health, Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | | | - Joseph Betancourt
- Harvard Medical School, Boston, Massachusetts, USA
- The Commonwealth Fund, New York, New York, USA
| | - Helen Burton-Murray
- Center for Neurointestinal Health, Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Kyle Staller
- Center for Neurointestinal Health, Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Braden Kuo
- Center for Neurointestinal Health, Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
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15
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Gawey BJ, Mars RA, Kashyap PC. The role of the gut microbiome in disorders of gut-brain interaction. FEBS J 2025; 292:1357-1377. [PMID: 38922780 PMCID: PMC11664017 DOI: 10.1111/febs.17200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Revised: 04/03/2024] [Accepted: 06/05/2024] [Indexed: 06/28/2024]
Abstract
Disorders of Gut-Brain Interaction (DGBI) are widely prevalent and commonly encountered in gastroenterology practice. While several peripheral and central mechanisms have been implicated in the pathogenesis of DGBI, a recent body of work suggests an important role for the gut microbiome. In this review, we highlight how gut microbiota and their metabolites affect physiologic changes underlying symptoms in DGBI, with a particular focus on their mechanistic influence on GI transit, visceral sensitivity, intestinal barrier function and secretion, and CNS processing. This review emphasizes the complexity of local and distant effects of microbial metabolites on physiological function, influenced by factors such as metabolite concentration, duration of metabolite exposure, receptor location, host genetics, and underlying disease state. Large-scale in vitro work has elucidated interactions between host receptors and the microbial metabolome but there is a need for future research to integrate such preclinical findings with clinical studies. The development of novel, targeted therapeutic strategies for DGBI hinges on a deeper understanding of these metabolite-host interactions, offering exciting possibilities for the future of treatment of DGBI.
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Affiliation(s)
- Brent J Gawey
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Ruben A Mars
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Purna C Kashyap
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
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16
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Katsumata R, Hosokawa T, Manabe N, Mori H, Wani K, Kimura M, Oda S, Ishii K, Tanikawa T, Urata N, Ayaki M, Nishino K, Murao T, Suehiro M, Fujita M, Kawanaka M, Haruma K, Kawamoto H, Takao T, Kamada T. Brain activity during a public-speaking situation in virtual reality in patients with irritable bowel syndrome and functional dyspepsia. J Gastroenterol 2025:10.1007/s00535-025-02228-w. [PMID: 39994039 DOI: 10.1007/s00535-025-02228-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 02/06/2025] [Indexed: 02/26/2025]
Abstract
BACKGROUND Psychosocial stress plays a central role in the pathophysiology of disorders of gut-brain interactions (DGBI), including functional dyspepsia (FD) and irritable bowel syndrome (IBS). Brain activity during psychosocial stress in patients with DGBI has not been adequately investigated. In this prospective study, we aimed to explore brain activity during psychosocial stress in patients with DGBI. METHODS Situations in an unmanned room, public space without attention, and public speaking were simulated in a virtual reality (VR) environment. Subjective stress, emotional state, and gastrointestinal (GI) symptoms were assessed using a visual analog scale, the State-Trait Anxiety Inventory, and the GI Symptom Rating Scale, respectively. Electrocardiograms were recorded to evaluate autonomic function. Activity in the prefrontal cortex (PFC) was examined using functional near-infrared spectroscopy (fNIRS). RESULTS Overall, 15 healthy controls, 15 patients with IBS, and 15 patients with FD were included. In the public-speaking scenario, subjective stress scores significantly decreased (indicating more stress) and sympathetic nervous activity increased equally among the three groups compared with those in an unmanned scene. Patients with IBS had higher activity in the left ventrolateral prefrontal cortex (VLPFC) and lower activity in the dorsolateral PFC (DLPFC) than those with FD and healthy controls. CONCLUSIONS Brain activity increased in the VLPFC and decreased in the DLPFC under stressful psychosocial situations created in the VR space in patients with IBS. Thus, the combination of VR and fNIRS is a viable option for evaluating brain activity under psychosocial stress in natural clinical settings.
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Affiliation(s)
- Ryo Katsumata
- Department of Health Care Medicine, Kawasaki Medical School General Medical Center, 2-6-1 Nakasange Kita-ku, Okayama City, Okayama, Japan.
| | - Takayuki Hosokawa
- Department of Orthoptics, Faculty of Rehabilitation, Kawasaki University of Medical Welfare, Kurashiki, Japan
| | - Noriaki Manabe
- Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Hitoshi Mori
- Department of Neurology, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Kenta Wani
- Department of Psychiatry, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Minako Kimura
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Shintaro Oda
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Katsunori Ishii
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Tomohiro Tanikawa
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Noriyo Urata
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Maki Ayaki
- Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Ken Nishino
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Takahisa Murao
- Department of Health Care Medicine, Kawasaki Medical School General Medical Center, 2-6-1 Nakasange Kita-ku, Okayama City, Okayama, Japan
| | - Mitsuhiko Suehiro
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Minoru Fujita
- Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Miwa Kawanaka
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Ken Haruma
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Hirofumi Kawamoto
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Toshihiro Takao
- Department of Health Care Medicine, Kawasaki Medical School, Kurashiki, Japan
| | - Tomoari Kamada
- Department of Health Care Medicine, Kawasaki Medical School General Medical Center, 2-6-1 Nakasange Kita-ku, Okayama City, Okayama, Japan
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Yu X, Chen X, Ouyang J, Xi B, Wu D, Wei L, Xie D, Shi Y. Exploring the mechanisms of Shugan-Jieyu-Jianpi formula against irritable bowel syndrome combined with non-alcoholic fatty liver disease by network pharmacology and experimental validation. Growth Factors 2025:1-19. [PMID: 39985335 DOI: 10.1080/08977194.2025.2467135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Accepted: 02/05/2025] [Indexed: 02/24/2025]
Abstract
The study was aimed to investigate the clinical effect and mechanism of Shugan-Jieyu-Jianpi (SGJYJP) formula for the treatment of irritable bowel syndrome (IBS) combined with non-alcoholic fatty liver disease (NAFLD). The clinical efficacy of SGJYJP was evaluated in 54 patients with IBS-NAFLD. The potential molecular mechanism of SGJYJP formula was investigated by network pharmacology. Animal models were constructed to explore the related mechanism. From clinical studies, the total effective rate of patients in SGJYJP group was significantly higher than that in pinaverium group. The protein expression of TGFB1 was declined in IBS-NAFLD rats, together with the increased expression of PTGS2 and TNF, which was abolished by SGJYJP treatment. SGJYJP significantly reduced the expression of TNF signalling related molecules of TRAF2, caspase-8, and elevated the expression of Bcl-xl in IBS-NAFLD animal models. SGJYJP may exert therapeutic effect on IBS-NAFLD by targeting PTGS2, TGFB1, and TNF genes and TNF signalling.
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Affiliation(s)
- Xiaowen Yu
- Department of Gastroenterology, Zhenjiang Hospital Affiliated to Nanjing University of Chinese Medicine, Zhenjiang Hospital of Traditional Chinese Medicine, Zhenjiang Traditional Chinese Medicine Spleen and Stomach Disease Clinical Medicine Research Center, Zhenjiang, China
| | - Xuan Chen
- Suzhou Science & Technology Town Hospital, Gusu School, Nanjing Medical University, Suzhou, China
| | - Jun Ouyang
- Department of Gastroenterology, Zhenjiang Hospital Affiliated to Nanjing University of Chinese Medicine, Zhenjiang Hospital of Traditional Chinese Medicine, Zhenjiang Traditional Chinese Medicine Spleen and Stomach Disease Clinical Medicine Research Center, Zhenjiang, China
| | - Biao Xi
- Department of Gastroenterology, Zhenjiang Hospital Affiliated to Nanjing University of Chinese Medicine, Zhenjiang Hospital of Traditional Chinese Medicine, Zhenjiang Traditional Chinese Medicine Spleen and Stomach Disease Clinical Medicine Research Center, Zhenjiang, China
| | - Defeng Wu
- Department of Gastroenterology, Zhenjiang Hospital Affiliated to Nanjing University of Chinese Medicine, Zhenjiang Hospital of Traditional Chinese Medicine, Zhenjiang Traditional Chinese Medicine Spleen and Stomach Disease Clinical Medicine Research Center, Zhenjiang, China
| | - Ling Wei
- Department of Laboratory, Zhenjiang Hospital Affiliated to Nanjing University of Chinese Medicine, Zhenjiang Hospital of Traditional Chinese Medicine, Zhenjiang, China
| | - Dongyu Xie
- Department of Gastroenterology, Zhenjiang Hospital Affiliated to Nanjing University of Chinese Medicine, Zhenjiang Hospital of Traditional Chinese Medicine, Zhenjiang Traditional Chinese Medicine Spleen and Stomach Disease Clinical Medicine Research Center, Zhenjiang, China
| | - Yaxiang Shi
- Department of Gastroenterology, Zhenjiang Hospital Affiliated to Nanjing University of Chinese Medicine, Zhenjiang Hospital of Traditional Chinese Medicine, Zhenjiang Traditional Chinese Medicine Spleen and Stomach Disease Clinical Medicine Research Center, Zhenjiang, China
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18
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Yu RL, Weber HC. Irritable bowel syndrome, the gut microbiome, and diet. Curr Opin Endocrinol Diabetes Obes 2025:01266029-990000000-00121. [PMID: 39968682 DOI: 10.1097/med.0000000000000905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/20/2025]
Abstract
PURPOSE OF REVIEW To provide an update of recent studies exploring the role of the gut microbiota and diet in the pathogenesis and treatment of irritable bowel syndrome (IBS). RECENT FINDINGS The human gut microbiome has been recognized as an important, active source of signaling molecules that explain in part the disorder of the gut brain interaction (DGBI) in IBS. Subsequent changes in the metabolome such as the production of short-chain fatty acids (SCFA) and serotonin are associated with IBS symptoms. Dietary components are recognized as important triggers of IBS symptoms and a diet low in fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) has been shown effective and safe, even when used long-term. Fecal microbiota transplantation (FMT) in IBS has not shown sustained and effective IBS symptom reduction in controlled clinical trials. SUMMARY This update elucidates recent developments in IBS as it relates to clinical trial results targeting dietary and gut microbiota interventions. The gut microbiome is metabolically active and affects the bi-directional signaling of the gut-brain axis.
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Affiliation(s)
- Rosa Lu Yu
- Boston University Chobanian & Avedisian School of Medicine
| | - H Christian Weber
- Boston University Chobanian & Avedisian School of Medicine
- VA Boston Healthcare System, Section of Gastroenterology and Hepatology, Boston, Massachusetts, USA
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Martín-Cardona A, Carrasco A, Ferrer C, González-Mínguez C, Luizaga-Velasco L, Tarroch X, Gonzalez-Puglia G, Tristán E, Cardozo-Rembado NB, Pallarès N, Tebé C, Arau B, Salvador I, Fajardo I, Rifà R, Ruiz L, Ruiz-Ramírez P, Fernández-Herrera S, Raga A, Aceituno M, Zabana Y, Loras C, Fonolleda M, Roigé J, Fernández-Bañares F, Esteve M. Histology of the Upper Gastrointestinal Tract, Morphometry and Lymphocyte Subpopulations of the Duodenal Mucosa: Insights from Healthy Individuals. Int J Mol Sci 2025; 26:1349. [PMID: 39941117 PMCID: PMC11818500 DOI: 10.3390/ijms26031349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Revised: 01/28/2025] [Accepted: 02/04/2025] [Indexed: 02/16/2025] Open
Abstract
The upper oesophagogastrointestinal (UEGI) tract histology, intestinal morphometry and lymphocyte subpopulations of healthy people is scarcely known. In research studies of inflammation involving the UEGI tract, there is a lack of adequate healthy controls. Aims: To evaluate the histology of the UEGI tract and the duodenal lymphocyte subpopulations of healthy volunteers and patients with gastroesophageal reflux disease (GERD), the latter to assess if it could replace healthy subjects. Healthy individuals were excluded if they had symptoms, comorbidities, pregnancy, toxics, medications or abnormal blood analysis. Subjects in both groups with abnormal duodenal intraepithelial lymphocyte (IEL) counts were also excluded. A total of 280 subjects were assessed, and 37 were included (23 healthy and 14 with GERD). The GERD group showed a higher IEL count (median [IQR]: 19.5 [17-22]), than healthy group: (15 [12-18]), p = 0.004. Eosinophils, mast cells and intestinal morphometry were similar in both groups. In the lamina propria, CD4+ T cells decreased (p = 0.008), and CD8+ T cells increased (p = 0.014). The total innate lymphoid cells (ILC) and CD3- cells decreased (p = 0.007) in GERD group compared to healthy controls. At the intraepithelial level, NKT cells increased (p = 0.036) and ILC3 decreased (p = 0.049) in the GERD group. This is the first study to comprehensively map the histology, morphometry and duodenal subpopulations of healthy volunteers to help define a "gold standard" of normality. The differences found between both groups suggest that, whenever possible, healthy subjects should be included in research studies. Alternatively, we can consider a well-defined homogenous group with GERD to serve as the control group.
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Affiliation(s)
- Albert Martín-Cardona
- Digestive Diseases Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (A.C.); (G.G.-P.); (E.T.); (N.B.C.-R.); (B.A.); (I.S.); (I.F.); (R.R.); (L.R.); (P.R.-R.); (A.R.); (M.A.); (Y.Z.); (C.L.); (F.F.-B.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Anna Carrasco
- Digestive Diseases Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (A.C.); (G.G.-P.); (E.T.); (N.B.C.-R.); (B.A.); (I.S.); (I.F.); (R.R.); (L.R.); (P.R.-R.); (A.R.); (M.A.); (Y.Z.); (C.L.); (F.F.-B.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Carme Ferrer
- Pathology Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (C.F.); (C.G.-M.); (L.L.-V.); (X.T.)
| | - Clarisa González-Mínguez
- Pathology Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (C.F.); (C.G.-M.); (L.L.-V.); (X.T.)
| | - Luis Luizaga-Velasco
- Pathology Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (C.F.); (C.G.-M.); (L.L.-V.); (X.T.)
| | - Xavier Tarroch
- Pathology Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (C.F.); (C.G.-M.); (L.L.-V.); (X.T.)
| | - Gerardo Gonzalez-Puglia
- Digestive Diseases Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (A.C.); (G.G.-P.); (E.T.); (N.B.C.-R.); (B.A.); (I.S.); (I.F.); (R.R.); (L.R.); (P.R.-R.); (A.R.); (M.A.); (Y.Z.); (C.L.); (F.F.-B.)
| | - Eva Tristán
- Digestive Diseases Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (A.C.); (G.G.-P.); (E.T.); (N.B.C.-R.); (B.A.); (I.S.); (I.F.); (R.R.); (L.R.); (P.R.-R.); (A.R.); (M.A.); (Y.Z.); (C.L.); (F.F.-B.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Natalia Berenice Cardozo-Rembado
- Digestive Diseases Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (A.C.); (G.G.-P.); (E.T.); (N.B.C.-R.); (B.A.); (I.S.); (I.F.); (R.R.); (L.R.); (P.R.-R.); (A.R.); (M.A.); (Y.Z.); (C.L.); (F.F.-B.)
| | - Natàlia Pallarès
- Biostatistics Support and Research Unit, Germans Trias I Pujol Research Institute and Hospital (IGTP), 08916 Badalona, Catalonia, Spain; (N.P.); (C.T.)
| | - Cristian Tebé
- Biostatistics Support and Research Unit, Germans Trias I Pujol Research Institute and Hospital (IGTP), 08916 Badalona, Catalonia, Spain; (N.P.); (C.T.)
| | - Beatriz Arau
- Digestive Diseases Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (A.C.); (G.G.-P.); (E.T.); (N.B.C.-R.); (B.A.); (I.S.); (I.F.); (R.R.); (L.R.); (P.R.-R.); (A.R.); (M.A.); (Y.Z.); (C.L.); (F.F.-B.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Isabel Salvador
- Digestive Diseases Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (A.C.); (G.G.-P.); (E.T.); (N.B.C.-R.); (B.A.); (I.S.); (I.F.); (R.R.); (L.R.); (P.R.-R.); (A.R.); (M.A.); (Y.Z.); (C.L.); (F.F.-B.)
| | - Ingrid Fajardo
- Digestive Diseases Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (A.C.); (G.G.-P.); (E.T.); (N.B.C.-R.); (B.A.); (I.S.); (I.F.); (R.R.); (L.R.); (P.R.-R.); (A.R.); (M.A.); (Y.Z.); (C.L.); (F.F.-B.)
| | - Raimon Rifà
- Digestive Diseases Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (A.C.); (G.G.-P.); (E.T.); (N.B.C.-R.); (B.A.); (I.S.); (I.F.); (R.R.); (L.R.); (P.R.-R.); (A.R.); (M.A.); (Y.Z.); (C.L.); (F.F.-B.)
| | - Laura Ruiz
- Digestive Diseases Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (A.C.); (G.G.-P.); (E.T.); (N.B.C.-R.); (B.A.); (I.S.); (I.F.); (R.R.); (L.R.); (P.R.-R.); (A.R.); (M.A.); (Y.Z.); (C.L.); (F.F.-B.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Pablo Ruiz-Ramírez
- Digestive Diseases Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (A.C.); (G.G.-P.); (E.T.); (N.B.C.-R.); (B.A.); (I.S.); (I.F.); (R.R.); (L.R.); (P.R.-R.); (A.R.); (M.A.); (Y.Z.); (C.L.); (F.F.-B.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Sònia Fernández-Herrera
- Digestive Diseases Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (A.C.); (G.G.-P.); (E.T.); (N.B.C.-R.); (B.A.); (I.S.); (I.F.); (R.R.); (L.R.); (P.R.-R.); (A.R.); (M.A.); (Y.Z.); (C.L.); (F.F.-B.)
| | - Agnès Raga
- Digestive Diseases Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (A.C.); (G.G.-P.); (E.T.); (N.B.C.-R.); (B.A.); (I.S.); (I.F.); (R.R.); (L.R.); (P.R.-R.); (A.R.); (M.A.); (Y.Z.); (C.L.); (F.F.-B.)
| | - Montserrat Aceituno
- Digestive Diseases Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (A.C.); (G.G.-P.); (E.T.); (N.B.C.-R.); (B.A.); (I.S.); (I.F.); (R.R.); (L.R.); (P.R.-R.); (A.R.); (M.A.); (Y.Z.); (C.L.); (F.F.-B.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Yamile Zabana
- Digestive Diseases Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (A.C.); (G.G.-P.); (E.T.); (N.B.C.-R.); (B.A.); (I.S.); (I.F.); (R.R.); (L.R.); (P.R.-R.); (A.R.); (M.A.); (Y.Z.); (C.L.); (F.F.-B.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Carme Loras
- Digestive Diseases Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (A.C.); (G.G.-P.); (E.T.); (N.B.C.-R.); (B.A.); (I.S.); (I.F.); (R.R.); (L.R.); (P.R.-R.); (A.R.); (M.A.); (Y.Z.); (C.L.); (F.F.-B.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Mireia Fonolleda
- Department of Immunology, Catlab, 08232 Viladecavalls, Catalonia, Spain;
| | - Jordi Roigé
- Department of Genetics, Catlab, 08232 Viladecavalls, Catalonia, Spain;
| | - Fernando Fernández-Bañares
- Digestive Diseases Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (A.C.); (G.G.-P.); (E.T.); (N.B.C.-R.); (B.A.); (I.S.); (I.F.); (R.R.); (L.R.); (P.R.-R.); (A.R.); (M.A.); (Y.Z.); (C.L.); (F.F.-B.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Maria Esteve
- Digestive Diseases Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Catalonia, Spain; (A.C.); (G.G.-P.); (E.T.); (N.B.C.-R.); (B.A.); (I.S.); (I.F.); (R.R.); (L.R.); (P.R.-R.); (A.R.); (M.A.); (Y.Z.); (C.L.); (F.F.-B.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
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Carvalho C, Rocha APR, Dos Santos GB, Guimarães JB, Amorim MN, Beleza ACS, Rodrigues-de-Souza DP, da Silva Serrão PRM, de Oliveira Sato T. Pelvic Floor Dysfunction and Associated Factors in Women with Systemic Autoimmune Rheumatic Diseases: A Cross-Sectional Study. Int Urogynecol J 2025:10.1007/s00192-025-06071-8. [PMID: 39903236 DOI: 10.1007/s00192-025-06071-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 01/14/2025] [Indexed: 02/06/2025]
Abstract
INTRODUCTION AND HYPOTHESIS Systemic autoimmune rheumatic diseases (SARDs) cause musculoskeletal disorders and are associated with various issues that affect the quality of life. Since the musculoskeletal system is affected, the pelvic floor muscles can also be impacted, leading to possible pelvic floor dysfunctions (PFDs). Thus, the purpose of this study was to investigate the presence of PFDs, such as urinary incontinence (UI), anal incontinence (AI), genital-pelvic pain/penetration disorder (GPPPD), and pelvic organ prolapse (POP) symptoms in women with SARDs compared to a control group composed of women without SARDs; and investigate the association between SARDs and PFDs. METHODS An online cross-sectional survey was carried out. Using a web-based questionnaire, data on demographic and anthropometric features, PFD (UI, nocturia, AI, GPPPD, and POP), and obstetric history were gathered. For quantitative variables, the Mann-Whitney U test was used, and for categorical variables, the chi-squared test was used for comparison between groups. The association between SARDs and PFD was investigated using logistic regression analysis. RESULTS The questionnaire was completed by 326 women (224 with SARDs and 102 healthy controls). Women with SARDs reported significantly more symptoms of PFD, UI, nocturia, AI (flatus and fecal incontinence), POP, and GPPPD than healthy controls. SARDs were associated with PFD, flatus incontinence, fecal incontinence, dyspareunia, and vaginismus. CONCLUSIONS PFD was much more common in women with SARDs than in healthy women. Women with SARDs were 1.8 to 5.2 times more likely than the control group to report PFD symptoms than women without SARDs.
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Affiliation(s)
- Cristiano Carvalho
- Department of Biosciences, Federal University of São Paulo, Campus Baixada Santista, Rua Silva Jardim, 136, Santos, SP, 11015-020, Brazil.
- Department of Physical Therapy, Federal University of São Carlos, São Carlos, SP, Brazil.
| | | | | | - Júlia Barbosa Guimarães
- Department of Biosciences, Federal University of São Paulo, Campus Baixada Santista, Rua Silva Jardim, 136, Santos, SP, 11015-020, Brazil
| | - Mariana Nobrega Amorim
- Department of Biosciences, Federal University of São Paulo, Campus Baixada Santista, Rua Silva Jardim, 136, Santos, SP, 11015-020, Brazil
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Sun Q, Weng RX, Li YC, Jia SM, Ma CT, Zhang HH, Tang Y, Li R, Xu GY. Potentiation of visualized exosomal miR-1306-3p from primary sensory neurons contributes to chronic visceral pain via spinal P2X3 receptors. Pain 2025:00006396-990000000-00814. [PMID: 39907482 DOI: 10.1097/j.pain.0000000000003537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 12/31/2024] [Indexed: 02/06/2025]
Abstract
ABSTRACT Exosomes served as "communicators" to exchange information among different cells in the nervous system. Our previous study demonstrated that the enhanced spinal synaptic transmission contributed to chronic visceral pain in irritable bowel syndrome. However, the underlying mechanism of primary sensory neuron (PSN)-derived exosomes on spinal transmission remains unclear. In this study, an exosome visualization method was established to specifically track exosomes derived from PSNs in CD63-GFPf/+ (green fluorescent protein) mice. Neonatal maternal deprivation (NMD) was adopted to induce chronic visceral pain in CD63-GFPf/+ male mice. The exosome visualization technology demonstrated that NMD increased visible PSN-derived exosomes in the spinal dorsal horn, enhanced spinal synaptic transmission, and led to visceral pain in CD63-GFPf/+ male mice. The PSN-derived exosomal miR-1306-3p sorted from spinal dorsal horn activated P2X3R, enhanced spinal synaptic transmission, and led to visceral pain in NMD mice. Moreover, upregulation of Rab27a in dorsal root ganglia mediated the increased release of PSN-derived exosomes, and intrathecal injection of siR-Rab27a reduced visible PSN-derived exosomes in spinal cord, suppressed spinal synaptic transmission, and alleviated visceral pain in NMD mice. This and future studies would reveal the detailed mechanisms of PSN-derived exosomes and provide a potential target for clinical treatment of chronic visceral pain in patients with irritable bowel syndrome.
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Affiliation(s)
- Qian Sun
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, P. R. China
- Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, P. R. China
| | - Rui-Xia Weng
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, P. R. China
| | - Yong-Chang Li
- Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, P. R. China
| | - Shu-Man Jia
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, P. R. China
| | - Chun-Tao Ma
- Department of Gastroenterology, Suzhou Xiangcheng People's Hospital, Suzhou, P. R. China
| | - Hong-Hong Zhang
- Department of Endocrinology, the Second Affiliated Hospital, Soochow University, Suzhou, P. R. China
| | - Yong Tang
- International Collaborative Centre on Big Science Plan for Purine Signaling, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Rui Li
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, P. R. China
| | - Guang-Yin Xu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, P. R. China
- Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, P. R. China
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22
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Armstrong D, Hungin AP, Kahrilas PJ, Sifrim D, Moayyedi P, Vaezi MF, Al‐Awadhi S, Anvari S, Bell R, Delaney B, Emura F, Gyawali CP, Katelaris P, Lazarescu A, Lee YY, Repici A, Roman S, Rooker CT, Savarino EV, Sinclair P, Sugano K, Yadlapati R, Yuan Y, Zerbib F, Sharma P. Management of Patients With Refractory Reflux-Like Symptoms Despite Proton Pump Inhibitor Therapy: Evidence-Based Consensus Statements. Aliment Pharmacol Ther 2025; 61:636-650. [PMID: 39740235 PMCID: PMC11754941 DOI: 10.1111/apt.18420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 04/16/2024] [Accepted: 11/18/2024] [Indexed: 01/02/2025]
Abstract
BACKGROUND Many patients diagnosed with gastro-oesophageal reflux disease (GERD) have persistent symptoms despite proton pump inhibitor (PPI) therapy. AIMS The aim of this consensus is to provide evidence-based statements to guide clinicians caring for patients with refractory reflux-like symptoms (rRLS) or refractory GERD. METHODS This consensus was developed by the International Working Group for the Classification of Oesophagitis. The steering committee developed specific PICO questions pertaining to the management of PPI rRLS. Methodologists conducted systematic reviews of the literature. The quality of evidence and strength of recommendations were rated using the GRADE approach. RESULTS Consensus was reached on 13 of 17 statements on diagnosis and management. For rRLS, suggested diagnostic strategies included endoscopy, ambulatory reflux testing and oesophageal manometry. The group did not reach consensus on the role of oesophageal biopsies or the use of reflux-symptom association in patients undergoing reflux testing. The group suggested against increasing the PPI dose in patients who had received 8 weeks of a twice-daily PPI. Adjunctive alginate or antacid therapy was suggested. There was no consensus on the role of adjunctive prokinetics. There was little role for adjunctive transient lower oesophageal sphincter relaxation (TLESR) inhibitors or bile acid sequestrants. Endoscopic or surgical anti-reflux procedures should not be performed in patients with rRLS in the absence of objectively confirmed GERD. CONCLUSIONS The management of rRLS should be personalised, based on shared decision-making regarding the role of diagnostic testing to confirm or rule out GERD as a basis for treatment optimisation. Anti-reflux procedures should not be performed without objective confirmation of GERD.
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Affiliation(s)
- David Armstrong
- Division of Gastroenterology & Farncombe Family Digestive Health Research InstituteMcMaster UniversityHamiltonOntarioCanada
| | - A. Pali Hungin
- Faculty of Medical SciencesNewcastle UniversityNewcastle upon TyneUK
| | - Peter J. Kahrilas
- Division of GastroenterologyNorthwestern UniversityChicagoIllinoisUSA
| | - Daniel Sifrim
- Barts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUK
| | - Paul Moayyedi
- Division of Gastroenterology & Farncombe Family Digestive Health Research InstituteMcMaster UniversityHamiltonOntarioCanada
| | - Michael F. Vaezi
- Division of GastroenterologyVanderbilt University Medical CenterNashvilleTennesseeUSA
| | - Sameer Al‐Awadhi
- Department of GastroenterologyRashid Hospital, Dubai Academic Health CorporationDubaiUAE
| | - Sama Anvari
- Division of Gastroenterology & Farncombe Family Digestive Health Research InstituteMcMaster UniversityHamiltonOntarioCanada
| | - Reginald Bell
- Institute of Esophageal and Reflux SurgeryEnglewoodColoradoUSA
| | - Brendan Delaney
- Department of Surgery and CancerImperial College London, Saint Mary's CampusLondonUK
| | - Fabian Emura
- Digestive Health and Liver Diseases, Miller School of MedicineUniversity of MiamiMiamiFloridaUSA
- Gastroenterology Division, Universidad de La Sabana, ChiaCundinamarcaColombia
| | - C. Prakash Gyawali
- Division of GastroenterologyWashington University School of MedicineSt. LouisMissouriUSA
| | - Peter Katelaris
- Gastroenterology DepartmentConcord Hospital, University of SydneySydneyNew South WalesAustralia
| | - Adriana Lazarescu
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine and DentistryUniversity of AlbertaEdmontonAlbertaCanada
| | - Yeong Yeh Lee
- GI Function & Motility UnitHospital Universiti Sains MalaysiaKota BharuMalaysia
| | - Alessandro Repici
- Department of GastroenterologyIRCCS Istituto Clinico HumanitasRozzano (Milano)Italy
| | - Sabine Roman
- Division of Digestive PhysiologyCentre Hospitalier Universitaire de LyonLyonFrance
| | - Ceciel T. Rooker
- International Foundation for Functional Gastrointestinal Disorders (IFFGD)Mount PleasantSouth CarolinaUSA
| | | | | | - Kentaro Sugano
- Division of Gastroenterology, Department of MedicineJichi Medical UniversityTochigi‐kenJapan
| | - Rena Yadlapati
- Division of GastroenterologyUniversity of California San DiegoLa JollaCaliforniaUSA
| | - Yuhong Yuan
- Division of Gastroenterology & Farncombe Family Digestive Health Research InstituteMcMaster UniversityHamiltonOntarioCanada
| | - Frank Zerbib
- CHU de Bordeaux, Centre Médico‐Chirurgical Magellan, Hôpital Haut‐Levêque, Department of GastroenterologyUniversité de Bordeaux, INSERM CIC 1401BordeauxFrance
| | - Prateek Sharma
- Division of Gastroenterology and HepatologyUniversity of Kansas School of Medicine, and Kansas City VA Medical CenterKansas CityMissouriUSA
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Prospero L, Riezzo G, D'Attoma B, Ignazzi A, Bianco A, Franco I, Curci R, Campanella A, Bagnato CB, Porcelli P, Giannelli G, Russo F. The impact of locus of control on somatic and psychological profiles of patients with irritable bowel syndrome engaging in aerobic exercise. Sci Rep 2025; 15:3966. [PMID: 39893252 PMCID: PMC11787329 DOI: 10.1038/s41598-025-88466-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Accepted: 01/28/2025] [Indexed: 02/04/2025] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic and recurrent disorder characterized by gastrointestinal (GI) symptoms and psychological disorders. Individuals with an external locus of control (LoC), a personality trait influencing one's actions and outcomes, are more vulnerable to IBS. Physical activity can deal with GI symptoms, preserving mental and physical health. In this context, our study aimed to investigate differences in symptom and psychological profiles among IBS patients classified by internal or external LoC when patients engaged in an aerobic exercise program (AEP). Each IBS patient was administered the International Physical Activity Questionnaire-Short Form (IPAQ-SF) before treatment, and the Physical Capacity Assessment Tests were applied before and after treatment. Participants filled out a GI symptom questionnaire before and after the intervention and some validated psychological tests to evaluate the changes induced by AEP. The AEP consisted of 180 min of moderate-intensity aerobic walking activity a week. Fifty-four IBS patients completed the 12-week study; 37 belonged to the internal LoC group and 17 to the external one. The internal LoC subgroup had a higher percentage of physically active subjects and a better physical capacity at baseline than those with external LoC. Only patients with an internal LoC achieved a statistically significant increase in physical capacity as the effect of the AEP. However, there was no statistically significant difference when Delta was considered. The somatic and psychological health status of IBS patients in the external LoC group was poorer than that of the internal LoC group at the baseline, particularly abdominal pain, psychosocial functioning, and emotional distress. After AEP, patients showed significant improvement in scores on the IBS-related and psychological scales, regardless of whether they belonged to the external or internal LoC. The present study confirmed the importance of considering both the GI symptoms and the psychological profile when dealing with IBS. AEP organized in walking groups has shown significant improvements for all IBS patients. Since external LoC was associated with poorer health status, individually tailored interventions should be planned to increase patients' self-motivation to treatment.Trial registration: registration number NCT05453084. First Posted Date 12/07/2022.
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Grants
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
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Affiliation(s)
- Laura Prospero
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology, IRCCS "Saverio de Bellis", Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Giuseppe Riezzo
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology, IRCCS "Saverio de Bellis", Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Benedetta D'Attoma
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology, IRCCS "Saverio de Bellis", Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Antonia Ignazzi
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology, IRCCS "Saverio de Bellis", Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Antonella Bianco
- Laboratory of Movement and Wellness, National Institute of Gastroenterology, IRCCS "Saverio de Bellis"", 70013, Castellana Grotte, BA, Italy
| | - Isabella Franco
- Laboratory of Movement and Wellness, National Institute of Gastroenterology, IRCCS "Saverio de Bellis"", 70013, Castellana Grotte, BA, Italy
| | - Ritanna Curci
- Laboratory of Movement and Wellness, National Institute of Gastroenterology, IRCCS "Saverio de Bellis"", 70013, Castellana Grotte, BA, Italy
| | - Angelo Campanella
- Laboratory of Movement and Wellness, National Institute of Gastroenterology, IRCCS "Saverio de Bellis"", 70013, Castellana Grotte, BA, Italy
| | - Claudia Beatrice Bagnato
- Laboratory of Movement and Wellness, National Institute of Gastroenterology, IRCCS "Saverio de Bellis"", 70013, Castellana Grotte, BA, Italy
| | - Piero Porcelli
- Department of Psychology, University of Chieti-Pescara, 66100, Chieti, Italy
| | - Gianluigi Giannelli
- Scientific Direction, National Institute of Gastroenterology, IRCCS "Saverio de Bellis", 70013, Castellana Grotte, BA, Italy
| | - Francesco Russo
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology, IRCCS "Saverio de Bellis", Via Turi 27, 70013, Castellana Grotte, BA, Italy.
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24
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Erdrich S, Harnett JE. Oral Health Is Associated with Disorders of Gut-Brain Interaction in Adult Women. Dig Dis Sci 2025; 70:638-643. [PMID: 39779585 PMCID: PMC11839681 DOI: 10.1007/s10620-024-08826-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 12/23/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND The disorders of gut-brain interaction (DGBI) form a heterogeneous group of gastrointestinal disorders that, to date, have no organic basis. The role of oral health in the development of these disorders has not been explored. OBJECTIVE The objective of this study was to examine the relationship between oral health and the DGBI. METHODS Data obtained from 166 women with (n = 113) and without fibromyalgia (n = 55) during a prospective observational study conducted in New Zealand during 2022 was evaluated for correlations between oral health measures (WHO oral health questionnaire), and the DGBI (Rome IV survey). RESULTS Of the 166 women enrolled in the study, 122 (73.5%) met criteria for at least one DGBI. Women who met criteria for any of the esophageal, gastroduodenal, bowel, and anorectal disorders had significantly lower oral health scores (p < 0.001). For 12 specific DGBI, oral health scores were significantly lower (p < 0.05). Oral health scores were inversely associated with the number of DGBI detected in each participant (ρ = - 0.590, p < 0.001, 95% CI [- 0.69, - 0.48]). CONCLUSION The results of this study suggest there is an association between the oral health and the presence, type, and number of DGBIs in women. Further research to examine the nature of this relationship is required.
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Affiliation(s)
- Sharon Erdrich
- Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Building A15, Science Rd, Sydney, NSW, 2006, Australia.
| | - Joanna E Harnett
- Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Building A15, Science Rd, Sydney, NSW, 2006, Australia
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25
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Nabi Z, Basha J, Inavolu P, Goud R, Veligatla V, Tummuru SP, Cheripelli N, Arutla M, Ramchandani M, Darisetty S, Nageshwar Reddy D. Comprehensive analysis of nutritional parameters in patients with idiopathic achalasia: A prospective study in India. Indian J Gastroenterol 2025; 44:57-63. [PMID: 39158832 DOI: 10.1007/s12664-024-01664-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 07/29/2024] [Indexed: 08/20/2024]
Abstract
BACKGROUND AND AIM Achalasia cardia, a primary motility disorder of the esophagus, poses significant malnutrition risks. This study aims at comprehensively assessing the nutritional status in untreated achalasia patients, contrasting it with functional gastrointestinal disorders (FGIDs) cases and impact of per-oral endoscopic myotomy (POEM) on nutrition at one-year. METHODS We conducted a prospective study, including consecutive achalasia cases, from December 2021 to April 2022 at a tertiary care centre. Biochemical parameters, anthropometry, subjective global assessment (SGA) and malnutrition universal screening tool were used for nutritional assessment. Cases diagnosed with FGIDs served as controls. RESULTS As many as 118 cases (41.2 ± 13.9 years, 61% males) with achalasia and 200 controls (43.4 ± 11.9 years, 69% males) were included in the study. Sub-types of achalasia included type I (16.9%), II (76.3%) and III (6.8%). Overall, 38.1% and 6.8% cases were moderately and severely malnourished, respectively. As compared to controls, cases with achalasia had lower pre-albumin (19.4 vs. 25.2; p = 0.001), serum calcium (p = 0.012), vitamin D (p = 0.001), serum iron (p = 0.001), triceps fold thickness (p = 0.002) and hand-grip strength (p = 0.001). On univariate analysis, type-I achalasia, body mass index, % weight loss, lower esophageal sphincter pressures and Eckardt scores were predictors of malnourishment (SGA). On multivariate analysis, type of achalasia, mid arm circumference and low body mass index were significant predictors of malnourishment in cases with achalasia. There was significant improvement in the nutritional status after POEM at one-year follow-up. CONCLUSION Achalasia patients demonstrate a notably higher risk of malnutrition compared to individuals with FGIDs. Nutritional status significantly improves after POEM. (NCT05161923).
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Affiliation(s)
- Zaheer Nabi
- Asian Institute of Gastroenterology, 6-3-661, Hyderabad, 500 082, India.
| | - Jahangeer Basha
- Asian Institute of Gastroenterology, 6-3-661, Hyderabad, 500 082, India
| | - Pradev Inavolu
- Asian Institute of Gastroenterology, 6-3-661, Hyderabad, 500 082, India
| | - Rajesh Goud
- Asian Institute of Gastroenterology, 6-3-661, Hyderabad, 500 082, India
| | | | | | | | - Madhulika Arutla
- Department of Clinical Nutrition, Asian Institute of Gastroenterology, Hyderabad 500 082, India
| | - Mohan Ramchandani
- Asian Institute of Gastroenterology, 6-3-661, Hyderabad, 500 082, India
| | | | - D Nageshwar Reddy
- Asian Institute of Gastroenterology, 6-3-661, Hyderabad, 500 082, India
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26
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Wang H, Zhao B, Huang L, Zhu X, Li N, Huang C, Han Z, Ouyang K. Conditional deletion of IP 3R1 by Islet1-Cre in mice reveals a critical role of IP 3R1 in interstitial cells of Cajal in regulating GI motility. J Gastroenterol 2025; 60:152-165. [PMID: 39476178 DOI: 10.1007/s00535-024-02164-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 10/16/2024] [Indexed: 02/05/2025]
Abstract
BACKGROUND AND AIMS Inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) has been proposed to play a physiological role in regulating gastrointestinal (GI) motility, but the underlying cell-dependent mechanism remains unclear. Here, we utilized cell-specific IP3R1 deletion strategies to address this question in mice. METHODS Conditional IP3R1 knockout mice using Wnt1-Cre, Islet1-Cre mice, and smMHC-CreEGFP were generated. Cell lineage tracing was performed to determine where gene deletion occurred in the GI tract. Whole-gut transit assay and isometric tension recording were used to assess GI function in vivo and in vitro. RESULTS In the mouse GI tract, Islet1-Cre targeted smooth muscle cells (SMCs) and interstitial cells of Cajal (ICCs), but not enteric neurons. IP3R1 deletion by Islet1-Cre (isR1KO) caused a phenotype of intestinal pseudo-obstruction (IPO), evidenced by prolonged whole-gut transit time, enlarged GI tract, abdominal distention, and early lethality. IP3R1 deletion by Islet1-Cre not only reduced the frequency of spontaneous contractions but also decreased the contractile responses to the muscarinic agonist carbachol (CCh) and electrical field stimulation (EFS) in colonic circular muscles. By contrast, smMHC-CreEGFP only targeted SMCs in the mouse GI tract. Although IP3R1 deletion by smMHC-CreEGFP (smR1KO) also reduced the contractile responses to CCh and EFS in colonic circular muscles, the frequency of spontaneous contractions was less affected, and neither global GI abnormalities nor early lethality was found in smR1KO mice. CONCLUSIONS IP3R1 deletion in both ICCs and SMCs but not in SMCs alone causes an IPO phenotype, suggesting that IP3R1 in ICCs plays an essential role in regulating GI motility in vivo.
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Affiliation(s)
- Hong Wang
- Central Laboratory, Peking University Shenzhen Hospital, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Peking University, Shenzhen, 518036, China
| | - Beili Zhao
- Central Laboratory, Peking University Shenzhen Hospital, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Peking University, Shenzhen, 518036, China
| | - Lei Huang
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Peking University, Shenzhen, 518036, China
| | - Xiangbin Zhu
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Peking University, Shenzhen, 518036, China
| | - Na Li
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Peking University, Shenzhen, 518036, China
| | - Can Huang
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Peking University, Shenzhen, 518036, China
| | - Zhen Han
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Peking University, Shenzhen, 518036, China.
| | - Kunfu Ouyang
- Central Laboratory, Peking University Shenzhen Hospital, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Peking University, Shenzhen, 518036, China.
- Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Peking University, Shenzhen, 518036, China.
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27
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Chen S, Shen C, Zeng X, Sun L, Luo F, Wan R, Zhang Y, Chen X, Hou Y, Wang W, Zheng Q, Li Y. Energy metabolism and the intestinal barrier: implications for understanding and managing intestinal diseases. Front Microbiol 2025; 16:1515364. [PMID: 39959156 PMCID: PMC11826063 DOI: 10.3389/fmicb.2025.1515364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 01/13/2025] [Indexed: 02/18/2025] Open
Abstract
The interplay between energy metabolism and the gut barrier is crucial for maintaining intestinal physiological homeostasis. Energy metabolism and the intestinal barrier perform distinct yet complementary roles that uphold intestinal ecological equilibrium. Disruptions in energy metabolism can compromise the integrity of the intestinal barrier; for example, inactivation of the AMPK pathway may lead to reduced expression of proteins associated with tight junctions. Conversely, impairment of the intestinal barrier can result in metabolic dysregulation, such as alterations in the gut microbiota that impede the production of short-chain fatty acids (SCFAs), which are essential substrates for energy metabolism. This disruption can affect energy production and modify the gut's hypoxic environment. Imbalances in these systems have been associated with the onset of various intestinal diseases. Research indicates that dietary interventions, such as a low FODMAP diet, can enhance the colonization of probiotics and improve the fermentation metabolism of SCFAs. Pharmacological strategies to elevate SCFA levels can activate the AMPK pathway and rectify abnormalities in energy metabolism. This review provides a comprehensive summary of recent advancements in elucidating the interactions between energy metabolism and the intestinal barrier.
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Affiliation(s)
- Shuai Chen
- Acupuncture and Tuina College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Caifei Shen
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Xiaorui Zeng
- Acupuncture and Tuina College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Luqiang Sun
- Acupuncture and Tuina College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Fangli Luo
- Acupuncture and Tuina College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Renhong Wan
- Acupuncture and Tuina College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Yupeng Zhang
- Acupuncture and Tuina College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Xinyun Chen
- Acupuncture and Tuina College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Yujun Hou
- Acupuncture and Tuina College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Wen Wang
- Acupuncture and Tuina College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Qianhua Zheng
- Acupuncture and Tuina College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Ying Li
- Acupuncture and Tuina College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
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28
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Kuo B, Lee AA, Abell T, Attaluri A, Cline M, Hasler W, Ho V, Lembo A, Masoud A, McCallum R, Moshiree B, Quigley EMM, Rao SSC, Stocker A, Sanchez M, Sarosiek I, Surjanhata B, Zhou J, Chey WD. The Assessment of Gastrointestinal Transit by the Atmo Capsule: A Comparison With the SmartPill Capsule. Clin Gastroenterol Hepatol 2025:S1542-3565(25)00069-2. [PMID: 39889900 DOI: 10.1016/j.cgh.2024.12.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 12/10/2024] [Accepted: 12/13/2024] [Indexed: 02/03/2025]
Abstract
BACKGROUND & AIMS Wireless motility capsules (WMCs) can be used to assess gastrointestinal transit time to facilitate diagnosis and treatment of motility disorders. The Atmo Capsule is a novel WMC that measures gases (H2, CO2, O2) and temperature. We aimed to compare and evaluate the performance characteristics of the Atmo Capsule and the SmartPill Capsule (discontinued reference standard WMC) for measurement of gastric emptying time (GET) and colonic transit time (CTT) in patients with confirmed or suspected disordered gastrointestinal transit. METHODS Patients with symptoms indicative of an upper and/or lower gastrointestinal motility disorder ingested the 2 WMCs in a random order. Gastrointestinal transit times were assessed using Spearman correlation and Bland-Altman analysis. Device agreement was assessed for delayed GET (≥5 hours) and CTT (≥59 hours). RESULTS There were 213 participants from 12 sites, yielding 177 paired GET and 147 paired CTT measurements. The measurements for GET and CTT with the Atmo Capsule and SmartPill Capsule were strongly correlated (GET, R = 0.73, P < .01; CTT, R = 0.69, P < .01), and their observed biases were within 10% of the delayed transit margin. Both delayed GET (68/177) and CTT (56/147) were identified in 38% of participants, with 84% agreement for identification of both delayed GET (sensitivity 78%, specificity 86%) and CTT (sensitivity 67%, specificity 93%). No serious adverse device effects were reported. CONCLUSIONS The performance characteristics of the Atmo capsule for measurements of GET and CTT were equivalent to the reference standard WMC with a strong correlation and good device agreement. These results demonstrate that the Atmo Capsule is a valid method for evaluating gastrointestinal transit. CLINICALTRIALS gov number, NCT05718505.
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Affiliation(s)
- Braden Kuo
- Center for Neurointestinal Health, Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
| | - Allen A Lee
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Thomas Abell
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, Kentucky
| | - Ashok Attaluri
- Gastroenterology, Alliance for Multispecialty Research, Merriam, Kansas
| | - Michael Cline
- Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - William Hasler
- Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona
| | - Vincent Ho
- School of Medicine, Western Sydney University, Campbelltown, NSW, Australia
| | - Anthony Lembo
- Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Amir Masoud
- Neurogastroenterology and Motility Center, Hartford Healthcare, Fairfield, Connecticut; Connecticut GI PC, Rocky Hill, Connecticut
| | - Richard McCallum
- Gastroenterology, Texas Tech University Health Sciences Center, El Paso, Texas
| | - Baharak Moshiree
- Gastroenterology, Wake Forest University, Charlotte, North Carolina
| | - Eamonn M M Quigley
- Lynda K and David M Underwood Center for Digestive Health, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas
| | - Satish S C Rao
- Division of Gastroenterology/Hepatology, Augusta University, Augusta, Georgia
| | - Abigail Stocker
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, Kentucky
| | - Mayra Sanchez
- Neurogastroenterology and Motility Center, Hartford Healthcare, Fairfield, Connecticut; Connecticut GI PC, Rocky Hill, Connecticut
| | - Irene Sarosiek
- Gastroenterology, Texas Tech University Health Sciences Center, El Paso, Texas
| | - Brian Surjanhata
- Center for Neurointestinal Health, Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Jerry Zhou
- School of Medicine, Western Sydney University, Campbelltown, NSW, Australia
| | - William D Chey
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
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29
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Zhu YN, Ren YD, Li L, Niu YQ, Wang RR, Li M. Plasma levels of ghrelin, neuropeptide Y, and urocortin-1 in patients with different subtypes of functional dyspepsia. Shijie Huaren Xiaohua Zazhi 2025; 33:62-69. [DOI: 10.11569/wcjd.v33.i1.62] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 11/29/2024] [Accepted: 12/27/2024] [Indexed: 01/25/2025] Open
Abstract
BACKGROUND Functional dyspepsia (FD) is a common disease of the digestive system, and its burden on medical resources is increasing year by year. Brain-gut axis dysfunction is considered to be an important pathogenesis of the disease, and brain-gut peptide plays an important role in the regulation of the brain-gut axis. In this study, plasma levels of acyl ghrelin (AG), desacyl ghrelin (DAG), neuropeptide Y (NPY), and urocortin-1 (UCN-1) were measured, and generalized Anxiety Disorder Scale and Patient Health Questionnaire Depression Scale were used to assess the psychosocial status of patients to reveal their differences among different FD subtypes.
AIM To determine the plasma levels of AG, DAG, NPY and UCN-1 in patients with different subtypes of FD, and to investigate the psychosocial status of patients with FD, in order to find effective theoretical support for clinical treatment.
METHODS From February 2022 to March 2023, 53 patients with FD (all meeting Rome IV diagnostic criteria) were selected from the Department of Gastroenterology of the Second Hospital of Tianjin Medical University, including 19 cases in postprandial discomfort syndrome (PDS) group, 19 cases in overlap syndrome group, and 15 cases in epigastric pain syndrome (EPS) group. Fifteen healthy volunteers who underwent medical check-ups during the same time period were selected as a healthy control group. All study subjects were tested for plasma AG, DAG, NPY, and UCN-1 levels by enzyme-linked immunoassay, and four scales, namely, the Nepean Dyspepsia Symptom Index Rating Scale, Nepean Quality of Life Index Rating Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire Depression Scale, were used to assess the psychosocial status of the subjects.
RESULTS The level of serum AG in the PDS group was lower than those of the control (P < 0.001), EPS (P < 0.001), and overlap syndrome groups (P = 0.030). The level of serum AG in the overlap syndrome group was lower than those of the control (P = 0.017) and EPS groups (P = 0.008). However, no significant difference was found in serum AG between the EPS and control groups (P = 0.684). The differences in plasma DAG levels were not significant between the PDS and control groups (P = 0.458), between the EPS and control groups (P = 0.638), between the overlap syndrome and control groups (P = 0.612), between the PDS and EPS groups (P = 0.170), between the PDS and overlap syndrome groups (P = 0.709), and between the EPS and overlap syndrome groups (P = 0.239). The level of serum NPY in the PDS group was lower than those of the control (P = 0.043), EPS (P = 0.044), and overlap syndrome groups (P = 0.049), but no significant difference was found between the EPS and control groups (P = 0.971), between the EPS and overlap syndrome groups (P = 0.929), and between the overlap syndrome and control groups (P = 0.929). The level of serum UCN-1 in the PDS group was higher than those of the control (P = 0.036), EPS (P = 0.015), and overlap syndrome groups (P = 0.045), but no significant difference was found between the the EPS and control groups (P = 0.978), between the EPS and overlap syndrome groups (P = 0.571), and between the overlap syndrome and control groups (P = 0.649). The difference in the levels of anxiety and depression was statistically different between the FD group and the control group (P < 0.001), but the difference was not statistically significant between any two of the FD subgroups (P = 0.471 for anxiety, P = 0.171 for depression).
CONCLUSION Except between the EPS group and the healthy control group, the differences in plasma AG between any two of the other groups are statistically significant, suggesting that AG may be crucial in the pathogenesis of FD and its level can predict the clinical manifestations of FD. There is no significant difference in plasma DAG between any two of the groups, suggesting that DAG might not be involved in the pathogenesis of FD. Compared with the other three groups, the differences of plasma AG, NPY, and UCN-1 in the PDS group were statistically significant, suggesting that these three brain and intestinal peptides may be involved in the pathogenesis of PDS. FD patients are more likely to be complicated with anxiety and depression, and the more severe the dyspepsia symptoms of FD patients, the more serious the degree of anxiety and depression, and the greater the impact on the quality of life, suggesting that improving patients' emotional problems is very helpful to improve the long-term efficacy for FD.
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Affiliation(s)
- Ya-Na Zhu
- Department of Gastroenterology, The Second Hospital of Tianjin Medical University, Tianjin 300202, China
| | - Ya-Di Ren
- Department of Gastroenterology, Handan Central Hospital, Handan 056000, Hebei Province, China
| | - Lu Li
- Department of Gastroenterology, The Second Hospital of Tianjin Medical University, Tianjin 300202, China
| | - Yan-Qing Niu
- Department of Gastroenterology, The Second Hospital of Tianjin Medical University, Tianjin 300202, China
| | - Rao-Rao Wang
- Department of Gastroenterology, The Second Hospital of Tianjin Medical University, Tianjin 300202, China
| | - Man Li
- Department of Gastroenterology, The Second Hospital of Tianjin Medical University, Tianjin 300202, China
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30
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Zhu YN, Ren YD, Li L, Niu YQ, Wang RR, Li M. Plasma levels of ghrelin, neuropeptide Y, and urocortin-1 in patients with different subtypes of functional dyspepsia. Shijie Huaren Xiaohua Zazhi 2025; 33:60-67. [DOI: 10.11569/wcjd.v33.i1.60] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 11/29/2024] [Accepted: 12/27/2024] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Functional dyspepsia (FD) is a common disease of the digestive system, and its burden on medical resources is increasing year by year. Brain-gut axis dysfunction is considered to be an important pathogenesis of the disease, and brain-gut peptide plays an important role in the regulation of the brain-gut axis. In this study, plasma levels of acyl ghrelin (AG), desacyl ghrelin (DAG), neuropeptide Y (NPY), and urocortin-1 (UCN-1) were measured, and generalized Anxiety Disorder Scale and Patient Health Questionnaire Depression Scale were used to assess the psychosocial status of patients to reveal their differences among different FD subtypes.
AIM To determine the plasma levels of AG, DAG, NPY and UCN-1 in patients with different subtypes of FD, and to investigate the psychosocial status of patients with FD, in order to find effective theoretical support for clinical treatment.
METHODS From February 2022 to March 2023, 53 patients with FD (all meeting Rome IV diagnostic criteria) were selected from the Department of Gastroenterology of the Second Hospital of Tianjin Medical University, including 19 cases in postprandial discomfort syndrome (PDS) group, 19 cases in overlap syndrome group, and 15 cases in epigastric pain syndrome (EPS) group. Fifteen healthy volunteers who underwent medical check-ups during the same time period were selected as a healthy control group. All study subjects were tested for plasma AG, DAG, NPY, and UCN-1 levels by enzyme-linked immunoassay, and four scales, namely, the Nepean Dyspepsia Symptom Index Rating Scale, Nepean Quality of Life Index Rating Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire Depression Scale, were used to assess the psychosocial status of the subjects.
RESULTS The level of serum AG in the PDS group was lower than those of the control (P < 0.001), EPS (P < 0.001), and overlap syndrome groups (P = 0.030). The level of serum AG in the overlap syndrome group was lower than those of the control (P = 0.017) and EPS groups (P = 0.008). However, no significant difference was found in serum AG between the EPS and control groups (P = 0.684). The differences in plasma DAG levels were not significant between the PDS and control groups (P = 0.458), between the EPS and control groups (P = 0.638), between the overlap syndrome and control groups (P = 0.612), between the PDS and EPS groups (P = 0.170), between the PDS and overlap syndrome groups (P = 0.709), and between the EPS and overlap syndrome groups (P = 0.239). The level of serum NPY in the PDS group was lower than those of the control (P = 0.043), EPS (P = 0.044), and overlap syndrome groups (P = 0.049), but no significant difference was found between the EPS and control groups (P = 0.971), between the EPS and overlap syndrome groups (P = 0.929), and between the overlap syndrome and control groups (P = 0.929). The level of serum UCN-1 in the PDS group was higher than those of the control (P = 0.036), EPS (P = 0.015), and overlap syndrome groups (P = 0.045), but no significant difference was found between the the EPS and control groups (P = 0.978), between the EPS and overlap syndrome groups (P = 0.571), and between the overlap syndrome and control groups (P = 0.649). The difference in the levels of anxiety and depression was statistically different between the FD group and the control group (P < 0.001), but the difference was not statistically significant between any two of the FD subgroups (P = 0.471 for anxiety, P = 0.171 for depression).
CONCLUSION Except between the EPS group and the healthy control group, the differences in plasma AG between any two of the other groups are statistically significant, suggesting that AG may be crucial in the pathogenesis of FD and its level can predict the clinical manifestations of FD. There is no significant difference in plasma DAG between any two of the groups, suggesting that DAG might not be involved in the pathogenesis of FD. Compared with the other three groups, the differences of plasma AG, NPY, and UCN-1 in the PDS group were statistically significant, suggesting that these three brain and intestinal peptides may be involved in the pathogenesis of PDS. FD patients are more likely to be complicated with anxiety and depression, and the more severe the dyspepsia symptoms of FD patients, the more serious the degree of anxiety and depression, and the greater the impact on the quality of life, suggesting that improving patients' emotional problems is very helpful to improve the long-term efficacy for FD.
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Affiliation(s)
- Ya-Na Zhu
- Department of Gastroenterology, The Second Hospital of Tianjin Medical University, Tianjin 300202, China
| | - Ya-Di Ren
- Department of Gastroenterology, Handan Central Hospital, Handan 056000, Hebei Province, China
| | - Lu Li
- Department of Gastroenterology, The Second Hospital of Tianjin Medical University, Tianjin 300202, China
| | - Yan-Qing Niu
- Department of Gastroenterology, The Second Hospital of Tianjin Medical University, Tianjin 300202, China
| | - Rao-Rao Wang
- Department of Gastroenterology, The Second Hospital of Tianjin Medical University, Tianjin 300202, China
| | - Man Li
- Department of Gastroenterology, The Second Hospital of Tianjin Medical University, Tianjin 300202, China
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Lei Y, Sun X, Ruan T, Lu W, Deng B, Zhou R, Mu D. Effects of Probiotics and Diet Management in Patients With Irritable Bowel Syndrome: A Systematic Review and Network Meta-analysis. Nutr Rev 2025:nuae217. [PMID: 39862384 DOI: 10.1093/nutrit/nuae217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2025] Open
Abstract
CONTEXT The efficacy of probiotics and diet management in irritable bowel syndrome (IBS) is controversial, and their relative effectiveness remains unclear. OBJECTIVE This study aimed to evaluate the effects of probiotics, diet management, and their combination on IBS. DATA SOURCES PubMed, Embase, Cochrane, and Web of Science were searched from inception to July 10, 2023, for relevant studies, including symptom relief, IBS-symptom severity score (-SSS), and IBS-quality of life measure (-QOL). DATA EXTRACTION Two investigators independently performed the data extraction and quality assessment. DATA ANALYSIS A network meta-analysis was performed using a frequentist approach and a random-effects model to estimate the relative risk (RR) and 95% CI. RESULTS Forty-four articles were eligible for this study. In relieving IBS symptoms, compared with a sham diet, a low-fermentable oligosaccharide, disaccharide, monosaccharide, and polyols (low-FODMAP) diet (RR: 3.22; 95% CI: 1.70-6.26) and low-FODMAP diet combined with probiotics (RR: 17.79; 95% CI: 3.27-112.54) significantly relieved IBS symptoms. The control group showed significantly lower effectiveness than the probiotics group (RR: 0.47; 95% CI: 0.32-0.69). According to the surface under the cumulative rank curve (SUCRA), a low-FODMAP diet combined with probiotics (80.4%) had the best effect in relieving IBS symptoms, followed by a low-FODMAP diet (70.8%), probiotics (65.1%), and a gluten-free diet (54.3%). In reducing the total IBS-SSS, the low-FODMAP diet (90.5%) was the most effective, followed by the low-FODMAP diet combined with probiotics (76.6%), probiotics alone (62.3%), and gluten-free diet (28.3%). In reducing total IBS-QOL, probiotics (72.1%) ranked first, followed by gluten-free (57.0%) and low-FODMAP (56.9%) diets. Probiotics (34.9%) were associated with the lowest risk of adverse effects. CONCLUSION A low-FODMAP diet combined with probiotics is most effective in relieving IBS symptoms. A low-FODMAP diet is the most recommended diet for alleviating IBS severity, and probiotics were associated with improving the QOL of patients with IBS, with the fewest adverse events. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42024499113.
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Affiliation(s)
- Yupeng Lei
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan 610041, China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Xuemei Sun
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan 610041, China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Tiechao Ruan
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan 610041, China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Wenting Lu
- Integrated Care Management Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Bixin Deng
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan 610041, China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Ruixi Zhou
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan 610041, China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Dezhi Mu
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan 610041, China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China
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Brisinda G, Fico V, Tropeano G, Cariati M, Altieri G, Misuriello F, Pepe G, Fransvea P, Chiarello MM. Outlet type constipation in adult patients treated with type A botulinum toxin: a cohort study. Int J Colorectal Dis 2025; 40:22. [PMID: 39838040 PMCID: PMC11750880 DOI: 10.1007/s00384-024-04795-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/21/2024] [Indexed: 01/23/2025]
Abstract
PURPOSE Chronic constipation is a common symptom. Constipation due to pelvic floor disorders remain a therapeutic challenge. Biofeedback therapy is considered as the first-choice treatment for pelvic floor disorders, whenever dedicated expertise is available. Type A botulinum toxin has been used to selectively weaken the external anal sphincter and puborectalis muscle in constipated patients. METHOD Eighty-two patients with chronic outlet obstruction constipation were treated with 100 units type A botulinum toxin, injected into the puborectalis muscle and the external anal sphincter. RESULTS At the 2-month evaluation, a symptomatic improvement was noted in 69 patients. Seven (8.5%) patients had mild flatus incontinence. Stool frequency per week increased from 2.4 ± 0.9 to 5.1 ± 1.0 (P = 0.0001). Anorectal manometry demonstrated decreased tone during straining from 91 ± 28 mmHg to 61 ± 27 mmHg (P = 0.0001). Defecography after the treatment showed improvement in anorectal angle during straining, which increased from 96 ± 12° to 124 ± 14° (P = 0.0001). CONCLUSION Type A botulinum toxin relaxes the puborectalis muscle. Pressure values decline after the treatment. Transrectal ultrasonography to guide injections is a safe procedure. Repeated injections were needed to maintain the clinical improvement.
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Affiliation(s)
- Giuseppe Brisinda
- Catholic School of Medicine, "Agostino Gemelli", 00168, Rome, Italy.
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli, IRCCS, 00168, Rome, Italy.
| | - Valeria Fico
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli, IRCCS, 00168, Rome, Italy
| | - Giuseppe Tropeano
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli, IRCCS, 00168, Rome, Italy
| | - Maria Cariati
- Department of Surgery, Azienda Sanitaria Provinciale Crotone, 88900, Crotone, Italy
| | - Gaia Altieri
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli, IRCCS, 00168, Rome, Italy
| | | | - Gilda Pepe
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli, IRCCS, 00168, Rome, Italy
| | - Pietro Fransvea
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A Gemelli, IRCCS, 00168, Rome, Italy
| | - Maria Michela Chiarello
- Department of Surgery, Azienda Sanitaria Provinciale Crotone, 88900, Crotone, Italy
- Department of Surgery, Azienda Sanitaria Provinciale Cosenza, 87100, Cosenza, Italy
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Ricci C, Saracino IM, Valerii MC, Spigarelli R, Bellocchio I, Spisni E. Very-Low-Absorbable Geraniol for the Treatment of Irritable Bowel Syndrome: A "Real-World" Open-Label Study on 1585 Patients. Nutrients 2025; 17:328. [PMID: 39861460 PMCID: PMC11767699 DOI: 10.3390/nu17020328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 01/13/2025] [Accepted: 01/15/2025] [Indexed: 01/27/2025] Open
Abstract
OBJECTIVE The objective of this study was to evaluate the efficacy of a very-low-absorbable geraniol formulation, administered as a food supplement, in patients with irritable bowel syndrome (IBS) in a real-world setting in Italy. METHODS This open-label study was conducted in Italy on patients diagnosed with IBS and treated for 4 weeks with 240 mg/day of Palmarosa essential oil, absorbed on 960 mg of ginger root powder to obtain a very-low-absorbable geraniol formulation. Baseline characteristics, including demographic and symptoms were recorded using the IBS Severity Scoring System (IBS-SSS). After 28 ± 7 days, the patients were asked to complete the IBS-SSS questionnaire again. The primary objective was to confirm the effects of a very-low-absorbable geraniol formulation on self-reported symptoms of IBS and the quality of life of affected individuals. The secondary objective was to confirm the effect of the treatment on the different IBS subtypes. RESULTS A total of 1585 patients were included in the study, with a mean age of 44.8 years and 56.4% women. Following the 4-week supplementation period, significant decreases were observed in the patients' IBS-SSS (-67.9%) and all the primary IBS symptoms, such as abdominal distention (-82.3%), unsatisfaction with bowel habits (-46.2%), and interference with quality of life (QoL) (-64.9%) (all p < 0.01). The patients' stool type improved significantly. Treatment was effective in all IBS subtypes. CONCLUSIONS Treatment with very-low-adsorbable geraniol food supplement was associated with improvements in symptoms and bowel habits in all IBS subtypes in a real-world setting in Italy. These findings support the use of geraniol as an effective option for patients with IBS regardless of the disease subtype.
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Affiliation(s)
- Chiara Ricci
- Gastroenterology Unit, ASST Spedali Civili di Brescia, University of Brescia, Piazza del Mercato 15, 25121 Brescia, Italy;
| | - Ilaria Maria Saracino
- Microbiology Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy;
| | - Maria Chiara Valerii
- Department of Biological, Geological and Environmental Sciences, University of Bologna, Via Selmi 3, 40126 Bologna, Italy; (R.S.); (I.B.); (E.S.)
| | - Renato Spigarelli
- Department of Biological, Geological and Environmental Sciences, University of Bologna, Via Selmi 3, 40126 Bologna, Italy; (R.S.); (I.B.); (E.S.)
| | - Irene Bellocchio
- Department of Biological, Geological and Environmental Sciences, University of Bologna, Via Selmi 3, 40126 Bologna, Italy; (R.S.); (I.B.); (E.S.)
| | - Enzo Spisni
- Department of Biological, Geological and Environmental Sciences, University of Bologna, Via Selmi 3, 40126 Bologna, Italy; (R.S.); (I.B.); (E.S.)
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Cvetković M, Miladinović B, Branković S, Randjelović M, Živanović S, Kitić N, Milutinović M, Jovanović M, Stojanović D, Nikšić H, Šavikin K, Kitić D. Red Currant ( Ribes rubrum L.) Fruit Waste Extract and Juice as Potential Spasmolytic Agents. PLANTS (BASEL, SWITZERLAND) 2025; 14:234. [PMID: 39861587 PMCID: PMC11768213 DOI: 10.3390/plants14020234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/05/2025] [Accepted: 01/14/2025] [Indexed: 01/27/2025]
Abstract
Red currant (Ribes rubrum L.) berries are rich in bioactive compounds and exhibit nutritive and protective features. This research examined the content of secondary metabolites of the red currant variety Redpoll lyophilized juice and waste extract and their antioxidative and spasmolytic effects. The flavonol and anthocyanin contents of the samples were determined using high-performance liquid chromatography. The antispasmodic effects were assessed in in vitro conditions, and the potential impact of the samples and possible action mechanisms were revealed. The results showed the prevalence of cyanidin-3-O-glucoside as the dominant anthocyanin with higher content in the juice sample. Quercetin content, as the prevalent flavonol, was higher in the waste sample. The berry juice showed a greater ability for scavenging free radicals, whereas the waste better inhibited lipid peroxidation. The juice was a superior antispasmodic agent for spontaneous, KCl-, CaCl2-, BaCl2-, histamine-, and acetylcholine-induced ileal contractions. This first evaluation of the red currant variety Redpoll lyophilized juice and waste extract indicated the beneficial effects of juice as an antioxidant and spasmolytic agent. Therefore, this red currant juice sample could be designated for the prevention or treatment of gastrointestinal disorders.
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Affiliation(s)
- Maja Cvetković
- Department of Pharmacy, Faculty of Medicine, University of Niš, Dr. Zoran Djindjić Ave 81, 18000 Niš, Serbia; (M.C.); (M.R.); (M.M.); (M.J.); (D.K.)
| | - Bojana Miladinović
- Department of Pharmacy, Faculty of Medicine, University of Niš, Dr. Zoran Djindjić Ave 81, 18000 Niš, Serbia; (M.C.); (M.R.); (M.M.); (M.J.); (D.K.)
| | - Suzana Branković
- Department of Physiology, Faculty of Medicine, University of Niš, Dr. Zoran Djindjić Ave 81, 18000 Niš, Serbia;
| | - Milica Randjelović
- Department of Pharmacy, Faculty of Medicine, University of Niš, Dr. Zoran Djindjić Ave 81, 18000 Niš, Serbia; (M.C.); (M.R.); (M.M.); (M.J.); (D.K.)
| | - Slavoljub Živanović
- Biomedical Research Centre, Faculty of Medicine, University of Niš, Dr. Zoran Djindjić Ave 81, 18000 Niš, Serbia; (S.Ž.); (N.K.)
| | - Nemanja Kitić
- Biomedical Research Centre, Faculty of Medicine, University of Niš, Dr. Zoran Djindjić Ave 81, 18000 Niš, Serbia; (S.Ž.); (N.K.)
| | - Milica Milutinović
- Department of Pharmacy, Faculty of Medicine, University of Niš, Dr. Zoran Djindjić Ave 81, 18000 Niš, Serbia; (M.C.); (M.R.); (M.M.); (M.J.); (D.K.)
| | - Miloš Jovanović
- Department of Pharmacy, Faculty of Medicine, University of Niš, Dr. Zoran Djindjić Ave 81, 18000 Niš, Serbia; (M.C.); (M.R.); (M.M.); (M.J.); (D.K.)
| | - Dušica Stojanović
- Department of Social Medicine and Hygiene with Medical Ecology, Faculty of Medicine, University of Niš, Dr. Zoran Djindjić Ave 81, 18000 Niš, Serbia;
| | - Haris Nikšić
- Department of Pharmacognosy, Faculty of Pharmacy, University of Sarajevo, Zmaja od Bosne 8, 71000 Sarajevo, Bosnia and Herzegovina;
| | - Katarina Šavikin
- Institute for Medicinal Plants Research “Dr Josif Pančić”, Tadeuša Košćuška 1, 11000 Belgrade, Serbia;
| | - Dušanka Kitić
- Department of Pharmacy, Faculty of Medicine, University of Niš, Dr. Zoran Djindjić Ave 81, 18000 Niš, Serbia; (M.C.); (M.R.); (M.M.); (M.J.); (D.K.)
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Huang KY, Hu JY, Lv M, Wang FY, Ma XX, Tang XD, Lv L. Cerebral cortex changes in FD, IBS, and GERD: A Mendelian randomization study. J Affect Disord 2025; 369:1153-1160. [PMID: 39447977 DOI: 10.1016/j.jad.2024.10.057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 10/12/2024] [Accepted: 10/18/2024] [Indexed: 10/26/2024]
Abstract
BACKGROUND Prospective and cross-sectional studies have reported an association between functional gastrointestinal disorders and anxiety and depression. However, the causal relationship remains uncertain. To clarify this, we utilized Mendelian randomization (MR) to assess the causal effects of common gastrointestinal disorders on cortical structures. METHODS Genome-wide association study (GWAS) data was gathered for functional dyspepsia (FD), irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD) from European populations numbering 329,262, 16,792, and 602,604, respectively. GWAS cerebral cortical architecture data for cortical thickness (TH) and surface area (SA) were obtained from 51,665 MRI scans. MR was used to analyze the casual relationship between FD, IBS, GERD, and cortical structures. Inverse-variance weighted, weighted median, and MR-Egger tests were performed as assessment indicators. We also evaluated heterogeneity and pleiotropy. RESULTS FD significantly decreases the TH in the rostral anterior cingulate cortex (βTH = -0.022 mm; 95%CI: -0.035 mm to -0.009 mm2; PTH = 6.89 × 10-4), and IBS significantly decreases the SA of the pars triangularis (βSA = -21.91 mm2; 95%CI: -32.99 mm to -10.83 mm2; PSA = 1.06 × 10-4), precuneus (βSA = -47.53 mm2; 95%CI: -73.57 mm to-21.48 mm2; PSA = 3.48 × 10-4) and superior frontal regions (βSA = -78.70 mm2; 95%CI: -122.61 mm to -34.78 mm2; PSA = 4.4 × 10-4). At the local functional level, GERD significantly increases the SA of the inferior temporal region (βSA = -113.58 mm2, 95%CI: -113.58 mm to -39.01 mm2, PSA = 6.05 × 10-5). CONCLUSIONS FD, IBS and GERD can affect the cerebral cortex architecture through the brain-gut axis, potentially increasing the risks of mental illness and cognitive impairment.
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Affiliation(s)
- Kai-Yue Huang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China; Graduate School, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jia-Yan Hu
- Dongfang Hospital, Beijing University of Chinese Medicine, China
| | - Mi Lv
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China; Graduate School, China Academy of Chinese Medical Sciences, Beijing, China
| | - Feng-Yun Wang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiang-Xue Ma
- The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, China
| | - Xu-Dong Tang
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Lin Lv
- Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China.
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Jing C, Liu T, Li Q, Zhang C, Sun B, Yang X, You Y, Liu J, Yang H. Study of dynamic brain function in irritable bowel syndrome via Hidden Markov Modeling. Front Neurosci 2025; 18:1515540. [PMID: 39872994 PMCID: PMC11769953 DOI: 10.3389/fnins.2024.1515540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 12/27/2024] [Indexed: 01/30/2025] Open
Abstract
Background and purpose Irritable bowel syndrome (IBS) is a common bowel-brain interaction disorder whose pathogenesis is unclear. Many studies have investigated abnormal changes in brain function in IBS patients. In this study, we analyzed the dynamic changes in brain function in IBS patients using a Hidden Markov Model (HMM). Methods Resting-state functional magnetic resonance imaging (rs-fMRI) data and the clinical characteristics of 35 patients with IBS and 31 healthy controls (HCs) were collected. The rs-fMRI data of all participants were analyzed using HMM to identify recurrent brain activity states that evolve over time during the resting state. Additionally, the temporal properties of these HMM states and their correlations with clinical scale scores were examined. Result This study utilized the Hidden Markov Model (HMM) method to identify six distinct HMM states. Significant differences in fractional occupancy (FO) and lifetime (LT) were observed in states 5 and 6 between the IBS and HCs. The state transition probabilities differed between IBS and HCs, with an increased probability of transitioning from state 2 to state 6 in IBS patients. The reconfiguration of HMM states over time scales in IBS patients was associated with abnormal activity in the default mode network (DMN), sensorimotor network (SMN), and cingulo-opercular network (CON). Conclusion This study offers novel insights into the dynamic reorganization of brain activity patterns in IBS and elucidates potential links between these patterns and IBS-related emotional regulation and symptom experience, thereby contributing to a deeper understanding of the neural mechanisms underlying IBS.
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Affiliation(s)
- Chuan Jing
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Tianci Liu
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Qingzhou Li
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Chuan Zhang
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Baijintao Sun
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Xuezhao Yang
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Yutao You
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Jixin Liu
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi’an, China
| | - Hanfeng Yang
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
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Krynicka P, Kaczmarczyk M, Skonieczna-Żydecka K, Cembrowska-Lech D, Podsiadło K, Dąbkowski K, Gaweł K, Botke N, Zawada I, Ławniczak M, Białek A, Marlicz W. The burden of irritable bowel syndrome and functional dyspepsia in Poland: a cross-sectional study from West Pomeranian Voivodship. BMC Gastroenterol 2025; 25:8. [PMID: 39789471 PMCID: PMC11715971 DOI: 10.1186/s12876-024-03580-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 12/26/2024] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND Functional gastrointestinal disorders (FGIDs), now known as disorders of gut-brain interaction (DGBIs), such as Irritable Bowel Syndrome (IBS) and Functional Dyspepsia (FD), significantly impact global health, reducing quality of life and burdening healthcare systems. This study addresses the epidemiological gap in Poland, focusing on the West Pomeranian Voivodeship. METHODS We conducted a cross-sectional study of 2070 Caucasian patients (58.2% female, mean age 57.5 ± 15.1 years) undergoing gastrointestinal endoscopic examinations at Pomeranian Medical University from 2021 to 2023. Data were collected using Rome IV diagnostic questionnaires and correlated with gastroduodenoscopy and colonoscopy findings. Exclusion criteria were age under 18, pregnancy, Crohn's disease, ulcerative colitis, severe comorbidities, cancer, immunosuppressive therapy, ileostomy/colostomy, incomplete questionnaires, or lack of consent. RESULTS Using Rome IV criteria, IBS was diagnosed in 436 participants (21.1%) and FD in 248 participants (12.0%). Post-endoscopic evaluation revised FD diagnoses to 184 individuals (8.9%). Females had a higher prevalence of IBS and FD (OR 1.64 and 1.61, respectively). No significant association was found between higher BMI and increased risk of IBS and FD. Hypertension and diabetes prevalence were 35.1% and 13.0%, respectively. Individuals with a history of COVID-19 had a higher risk of developing IBS (OR 1.47, P = 0.050). CONCLUSIONS Our study provides crucial epidemiological data on IBS and FD in Poland, emphasizing the importance of endoscopic evaluations. Our findings highlight the need for regional studies to understand local DGBI prevalence, aiding targeted healthcare strategies.
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Affiliation(s)
- Patrycja Krynicka
- Department of Gastroenterology, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, Szczecin, 71-254, Poland
| | - Mariusz Kaczmarczyk
- Department of Biochemical Sciences, Pomeranian Medical University, Broniewskiego 24, Szczecin, 71-460, Poland
- Sanprobi sp. z o.o. sp. k, Kurza Stopka 5/c, Szczecin, 70-535, Poland
| | - Karolina Skonieczna-Żydecka
- Department of Biochemical Sciences, Pomeranian Medical University, Broniewskiego 24, Szczecin, 71-460, Poland
| | | | - Konrad Podsiadło
- Sanprobi sp. z o.o. sp. k, Kurza Stopka 5/c, Szczecin, 70-535, Poland
| | - Krzysztof Dąbkowski
- Department of Gastroenterology, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, Szczecin, 71-254, Poland
| | - Katarzyna Gaweł
- Department of Gastroenterology, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, Szczecin, 71-254, Poland
| | - Natalia Botke
- Department of Gastroenterology, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, Szczecin, 71-254, Poland
| | - Iwona Zawada
- Department of Gastroenterology, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, Szczecin, 71-254, Poland
| | - Małgorzata Ławniczak
- Department of Gastroenterology, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, Szczecin, 71-254, Poland
| | - Andrzej Białek
- Department of Gastroenterology, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, Szczecin, 71-254, Poland
| | - Wojciech Marlicz
- Department of Gastroenterology, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, Szczecin, 71-254, Poland.
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Skovslund Nielsen E, Kallesøe K, Bennedsen Gehrt T, Bjerre-Nielsen E, Lalouni M, Frostholm L, Bonnert M, Rask CU. Trajectories of Change, Illness Understanding, and Parental Worries in Children and Adolescents Undergoing Internet-Delivered Cognitive-Behavioral Therapy for Functional Abdominal Pain Disorders: Protocol for a Single-Case Design and Explorative Pilot Study. JMIR Res Protoc 2025; 14:e58563. [PMID: 39773759 PMCID: PMC11751652 DOI: 10.2196/58563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 08/08/2024] [Accepted: 11/12/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Functional abdominal pain disorders (FAPDs) are common in young people and are characterized by persistent or recurrent abdominal symptoms without apparent structural or biochemical abnormalities. FAPDs are associated with diminished quality of life, school absence, increased health care use, and comorbid anxiety and depression. Exposure-based internet-delivered cognitive behavioral therapy (ICBT) has demonstrated efficacy in alleviating abdominal symptoms and improving quality of life. However, a deeper understanding of effect mechanisms and identification of possible additional treatment targets could refine treatment. OBJECTIVE This protocol paper aims to describe a study focusing on children and adolescents undergoing ICBT for FAPDs, aiming to further investigate the underlying mechanisms of effect. METHODS Children (8-12 years), adolescents (13-17 years) with FAPDs, and their respective parents will be included for 10 weeks for ICBT. First, detailed trajectories of effect are examined through a randomized single-case design study involving 6 children and 6 adolescents (substudy 1). Following this, an open-ended explorative pilot study with 30 children and 30 adolescents explores potential illness-related cognitive biases and interoceptive accuracy before and after treatment (substudy 2). Finally, spanning across these 2 substudies, including all parents from substudies 1 and 2, we will assess parental distress and illness worries before and after treatment, and how these factors impact the treatment adherence and outcomes of the child or adolescent (substudy 3). RESULTS Recruitment of participants began in June 2022 and is finalized for substudy 1 and ongoing for substudies 2 and 3. Recruitment is expected to be completed by January 2025, with final data collection during April 2025. CONCLUSIONS The findings have the potential to contribute to the ongoing improvement of specialized psychological treatment for FAPDs in young people. TRIAL REGISTRATION ClinicalTrials.gov NCT05237882; https://clinicaltrials.gov/study/NCT05237882; ClinicalTrials.gov NCT05486585; https://clinicaltrials.gov/study/NCT05486585; OSF Registries osf.io/c49k7; https://osf.io/c49k7. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/58563.
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Affiliation(s)
- Eva Skovslund Nielsen
- Department of Child and Adolescent Psychiatry, Aarhus University Hospital, Aarhus N, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark
| | - Karen Kallesøe
- Department of Child and Adolescent Psychiatry, Aarhus University Hospital, Aarhus N, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark
| | - Tine Bennedsen Gehrt
- Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark
- Department of Research and Development, Prehospital Emergency Medical Services, Central Denmark Region, Aarhus N, Denmark
| | - Ellen Bjerre-Nielsen
- Department of Child and Adolescent Psychiatry, Aarhus University Hospital, Aarhus N, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark
| | - Maria Lalouni
- Division of Neuro, Department of Clinical Neuroscience, Karolinska Institutet, Solna, Sweden
- Center for Epidemiology and Community Medicine, Health Care Services Stockholm County, Stockholm, Sweden
| | - Lisbeth Frostholm
- Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark
- Department of Functional Disorders and Psychosomatics, Aarhus University Hospital, Aarhus N, Denmark
| | - Marianne Bonnert
- Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm, Sweden
| | - Charlotte Ulrikka Rask
- Department of Child and Adolescent Psychiatry, Aarhus University Hospital, Aarhus N, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark
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Fritz J, Coffey R, Bloch J, Cutler A, Gabrielson S, DiGiovanni S, Faherty LJ. The relationship between adverse childhood experiences and disorders of the gut-brain interaction. J Pediatr Gastroenterol Nutr 2025; 80:100-107. [PMID: 39584227 DOI: 10.1002/jpn3.12422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 08/07/2024] [Accepted: 09/11/2024] [Indexed: 11/26/2024]
Abstract
OBJECTIVES Disorders of the gut-brain interaction (DGBI) arise from a complex interplay of psychosocial factors, altered physiology, and early life factors. In adults, adverse childhood experiences (ACEs) have been associated with DGBI. While both ACEs and DGBI are prevalent among children, the relationship between ACEs and DGBI in childhood is not well understood. METHODS Retrospective review of patients aged 3-18 years with ACE scores documented between October 1, 2019 and April 30, 2022 who were divided into three comparison groups: (1) not referred to pediatric gastroenterology (GI); (2) referred to GI and diagnosed with a DGBI; and (3) referred to GI and not diagnosed with a DGBI. RESULTS Of 29,490 patients with ACE scores documented during the study period, 897 completed a GI consultation. Four hundred and one (44.7%) were diagnosed with a DGBI. With each additional adverse experience, patients were 1.09 times more likely to have a DGBI diagnosis (95% confidence interval [CI] = 1.056-1.163; p ≤ 0.001). An anxiety diagnosis mediated 73% of this relationship (p = 0.012). CONCLUSIONS Among patients receiving pediatric GI specialty care, higher ACE scores were associated with a higher likelihood of a DGBI diagnosis. Anxiety largely mediates this relationship, suggesting potential avenues for targeted, multidisciplinary interventions in both primary and specialty care settings.
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Affiliation(s)
- Julia Fritz
- Maine Medical Partners Pediatric Gastroenterology, Portland, Maine, USA
- Department of Pediatrics, Maine Medical Center, Portland, Maine, USA
- Tufts University School of Medicine, Boston, Massachusetts, USA
| | - Rachel Coffey
- Department of Pediatrics, Maine Medical Center, Portland, Maine, USA
| | - Jackson Bloch
- Maine Medical Partners Pediatric Gastroenterology, Portland, Maine, USA
| | - Anya Cutler
- MaineHealth Institute for Research Center for Interdisciplinary Population and Health Research, Portland, Maine, USA
| | - Sarah Gabrielson
- The Barbara Bush Children's Hospital at Maine Medical Center, Portland, Maine, USA
| | - Stephen DiGiovanni
- Department of Pediatrics, Maine Medical Center, Portland, Maine, USA
- Tufts University School of Medicine, Boston, Massachusetts, USA
| | - Laura J Faherty
- Department of Pediatrics, Maine Medical Center, Portland, Maine, USA
- Tufts University School of Medicine, Boston, Massachusetts, USA
- RAND Corporation, Boston, Massachusetts, USA
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Idalsoaga F, Ayares G, Blaney H, Cabrera D, Chahuan J, Monrroy H, Matar A, Halawi H, Arrese M, Arab JP, Díaz LA. Neurogastroenterology and motility disorders in patients with cirrhosis. Hepatol Commun 2025; 9:e0622. [PMID: 39773873 PMCID: PMC11717532 DOI: 10.1097/hc9.0000000000000622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 11/21/2024] [Indexed: 01/11/2025] Open
Abstract
Neurogastroenterology and motility disorders are complex gastrointestinal conditions that are prevalent worldwide, particularly affecting women and younger individuals. These conditions significantly impact the quality of life of people suffering from them. There is increasing evidence linking these disorders to cirrhosis, with a higher prevalence compared to the general population. However, the link between neurogastroenterology and motility disorders and cirrhosis remains unclear due to undefined mechanisms. In addition, managing these conditions in cirrhosis is often limited by the adverse effects of drugs commonly used for these disorders, presenting a significant clinical challenge in the routine management of patients with cirrhosis. This review delves into this connection, exploring potential pathophysiological links and clinical interventions between neurogastroenterology disorders and cirrhosis.
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Affiliation(s)
- Francisco Idalsoaga
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
- Department of Medicine, Division of Gastroenterology, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada
| | - Gustavo Ayares
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
- Universidad Finis Terrae, Escuela de Medicina, Facultad de Medicina, Universidad Fines Terrae, Santiago, Chile
| | - Hanna Blaney
- MedStar Georgetown University Hospital, Medstar Transplant Hepatology Institute, Washington, District of Columbia, USA
| | - Daniel Cabrera
- Faculty of Medicine, Universidad de los Andes, Santiago, Chile
- Centro de Estudios e Investigación en Salud y Sociedad, Escuela de Medicina, Facultad de Ciencias Médicas, Universidad Bernardo O Higgins, Santiago, Chile
| | - Javier Chahuan
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
| | - Hugo Monrroy
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
| | - Ayah Matar
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Houssam Halawi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Marco Arrese
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
| | - Juan Pablo Arab
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
- Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Luis Antonio Díaz
- Departamento De Gastroenterología, Escuela De Medicina, Pontificia Universidad Católica De Chile, Santiago, Chile
- MASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA
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Yang PL, Kamp KJ, Tu Q, Chen LJ, Cain K, Heitkemper MM, Burr RL. Relationship Between High Frequency Component of Heart Rate Variability and Delta EEG Power During Sleep in Women With Irritable Bowel Syndrome Compared to Healthy Women. Biol Res Nurs 2025; 27:60-70. [PMID: 39378890 DOI: 10.1177/10998004241288791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/10/2024]
Abstract
OBJECTIVE To explore the relationship between the high frequency (HF) heart rate variability (HRV) and electroencephalogram (EEG) delta band power in women with irritable bowel syndrome (IBS) versus healthy control women. MATERIALS AND METHODS Twenty women with IBS and twenty healthy controls were studied over three consecutive nights using polysomnography in a sleep laboratory. To avoid the first night effect, only second-night data were analyzed. Power spectral analysis was applied to HRV and EEG recordings. The linear system coherence/phase analysis assessed the relationship between normalized HF power of HRV and normalized delta band power of EEG during the first four NREM-REM sleep cycles. RESULTS Women with IBS exhibited a significantly higher percentage of NREM sleep, higher normalized HF, lower normalized low frequency (LF) and decreased LF/HF ratio of HRV in the first four NREM-REM sleep cycles compared to controls. Additionally, their normalized delta band power was significantly lower in these sleep cycles and over the whole night. The phase shift between HF and delta band power was significantly longer in the IBS group. While the coherence between normalized HF and normalized delta band power was lower in the IBS group, the difference was not statistically significant. CONCLUSIONS The coherence/phase analysis showed a dysregulated interaction between autonomic and central nervous systems in women with IBS, manifested by increased lag time between cardiac and EEG delta band power compared to healthy controls. Whether this dysregulation contributes to the pathophysiology of IBS remains to be determined.
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Affiliation(s)
- Pei-Lin Yang
- School of Nursing, National Defense Medical Center, Taipei, Taiwan (R.O.C.)
| | - Kendra J Kamp
- Department of Biobehavioral Nursing and Health Informatics, School of Nursing, University of Washington, Seattle, WA, USA
| | - Qian Tu
- MultiCare Health System, Pulmonary Specialists, Auburn, WA, USA
| | - Li Juen Chen
- Department of Biobehavioral Nursing and Health Informatics, School of Nursing, University of Washington, Seattle, WA, USA
- UW Medicine Valley Medical Center, Renton, WA, USA
| | - Kevin Cain
- Center for Biomedical Statistics, University of Washington, Seattle, WA, USA
| | - Margaret M Heitkemper
- Department of Biobehavioral Nursing and Health Informatics, School of Nursing, University of Washington, Seattle, WA, USA
| | - Robert L Burr
- Department of Biobehavioral Nursing and Health Informatics, School of Nursing, University of Washington, Seattle, WA, USA
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Park SC, Jung J, Kwon YE, Baeg SI, Oh DJ, Kim DH, Lee YK, Choi HM. Constipation and risk of death and cardiovascular events in patients on hemodialysis. Kidney Res Clin Pract 2025; 44:155-163. [PMID: 39815794 PMCID: PMC11838856 DOI: 10.23876/j.krcp.24.174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 10/02/2024] [Accepted: 10/24/2024] [Indexed: 01/18/2025] Open
Abstract
BACKGROUND Constipation is a common gastrointestinal disorder and is often accompanied by alteration in the gut microbiota. Recently, several studies have disclosed its association with an increased risk of cardiovascular disease and mortality in the general population. Despite the high prevalence of constipation, data on the clinical impact of constipation in patients with chronic kidney disease are limited. We aimed to explore the prevalence of constipation and its association with cardiovascular disease in chronic kidney disease using a nationally representative cohort of hemodialysis patients. METHODS This study used hemodialysis quality assessment and health insurance claims data from patients undergoing maintenance hemodialysis in South Korea. Chronic constipation was defined using the total number of laxatives prescribed during the 1-year baseline period. The primary outcome was a composite of acute ischemic stroke, hemorrhagic stroke, myocardial infarction, or all-cause death. Secondary outcomes were the individual components of the primary outcome. RESULTS Among 35,230 patients on hemodialysis, 9,133 (25.9%) were identified as having constipation. During a median follow-up of 5.4 years, patients with constipation had a 15% higher incidence of the composite outcome, 16% higher incidence of ischemic stroke, and 14% higher all-cause mortality, after multivariate adjustment. CONCLUSION Chronic constipation requiring laxatives was associated with a higher risk of the composite outcome of cardiovascular events or all-cause death in patients on hemodialysis. Further studies are needed to confirm whether constipation is an independent predictor or a possible causal factor of cardiovascular disease.
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Affiliation(s)
- Sang Cheol Park
- Artificial Intelligence and Robotics Laboratory, Myongji Hospital, Goyang, Republic of Korea
| | - Juyoung Jung
- Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang, Republic of Korea
| | - Young Eun Kwon
- Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang, Republic of Korea
| | - Song In Baeg
- Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang, Republic of Korea
| | - Dong-Jin Oh
- Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang, Republic of Korea
| | - Do Hyoung Kim
- Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Young-Ki Lee
- Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Hye Min Choi
- Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang, Republic of Korea
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Butt MF, Corsetti M. Editorial: Rebuilding Rome-Revising Diagnostic Criteria for Irritable Bowel Syndrome. Aliment Pharmacol Ther 2025; 61:392-393. [PMID: 39543836 DOI: 10.1111/apt.18400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 11/06/2024] [Accepted: 11/06/2024] [Indexed: 11/17/2024]
Affiliation(s)
- Mohsin F Butt
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK
| | - Maura Corsetti
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK
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Cyr M, Nahon I, Worman R, Cowley D, Hodges PW. Classification systems for chronic pelvic pain in males: a systematic review. BJU Int 2025; 135:22-30. [PMID: 39075791 PMCID: PMC11628891 DOI: 10.1111/bju.16485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/31/2024]
Abstract
OBJECTIVE To systematically review the classification systems for male chronic pelvic pain (CPP). METHODS The Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE), and Web of Science were searched. Any publication, with no restriction to publication date, was eligible. Publications had to propose a classification system for CPP in males or provide additional information of a system that had been identified. Systems were assessed with an adapted Critical Appraisal of Classification Systems tool. RESULTS A total of 33 relevant publications were identified, with 22 proposing an original classification system. Systems aimed to: (i) diagnose CPP and/or differentially diagnose CPP from other conditions, (ii) differentially diagnose subtypes within CPP, or (iii) identify features that could inform underlying mechanisms and/or treatment selection. Conditions referred to as chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis/bladder pain syndrome were most represented. Clinical signs/symptoms, pathoanatomical investigations, and presumed pain mechanisms were used for classification. Quality of systems was low to moderate, implying limitations to consider for their interpretation. CONCLUSIONS Many classification systems for CPP in males exist. Careful consideration of their intended purpose is required. Future work should examine whether outcomes for patients are improved when decisions are guided by their use.
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Affiliation(s)
- Marie‐Pierre Cyr
- School of Health and Rehabilitation SciencesThe University of QueenslandBrisbaneQueenslandAustralia
| | - Irmina Nahon
- Department of Physiotherapy, Faculty of HealthUniversity of CanberraCanberraAustralian Capital TerritoryAustralia
| | - Rachel Worman
- School of Health and Rehabilitation SciencesThe University of QueenslandBrisbaneQueenslandAustralia
| | - David Cowley
- School of Health and Rehabilitation SciencesThe University of QueenslandBrisbaneQueenslandAustralia
| | - Paul W. Hodges
- School of Health and Rehabilitation SciencesThe University of QueenslandBrisbaneQueenslandAustralia
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Khosravi M, Alzahrani AA, Muhammed TM, Hjazi A, Abbas HH, AbdRabou MA, Mohmmed KH, Ghildiyal P, Yumashev A, Elawady A, Sarabandi S. Management of Refractory Functional Gastrointestinal Disorders: What Role Should Psychiatrists Have? PHARMACOPSYCHIATRY 2025; 58:14-24. [PMID: 38897220 DOI: 10.1055/a-2331-7684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/21/2024]
Abstract
Currently, it has been stated that psychiatric and psychological problems are equally paramount aspects of the clinical modulation and manifestation of both the central nervous and digestive systems, which could be used to restore balance. The present narrative review aims to provide an elaborate description of the bio-psycho-social facets of refractory functional gastrointestinal disorders, psychiatrists' role, specific psychiatric approach, and the latest psychiatric and psychological perspectives on practical therapeutic management. In this respect, "psyche," "psychiatry," "psychology," "psychiatrist," "psychotropic," and "refractory functional gastrointestinal disorders" (as the keywords) were searched in relevant English publications from January 1, 1950, to March 1, 2024, in the PubMed, Web of Science, Scopus, EMBASE, Cochrane Library, and Google Scholar databases. Eventually, the narrative technique was adopted to reach a compelling story with a high level of cohesion through material synthesis. The current literature recognizes the brain-gut axis modulation as a therapeutic target for refractory functional gastrointestinal disorders and the bio-psycho-social model as an integrated framework to explain disease pathogenesis. The results also reveal some evidence to affirm the benefits of psychotropic medications and psychological therapies in refractory functional gastrointestinal disorders, even when psychiatric symptoms were absent. It seems that psychiatrists are required to pay higher levels of attention to both the assessment and treatment of patients with refractory functional gastrointestinal disorders, accompanied by educating and training practitioners who take care of these patients.
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Affiliation(s)
- Mohsen Khosravi
- Department of Psychiatry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
- Health Promotion Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
| | | | - Thikra M Muhammed
- Department of Biotechnology, College of Applied Sciences, University of Fallujah, Al-anbar, Iraq
| | - Ahmed Hjazi
- Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | - Huda H Abbas
- National University of Science and Technology, Dhi Qar, Iraq
| | - Mervat A AbdRabou
- Department of Biology, College of Science, Jouf University, Sakaka, Saudi Arabia
| | | | - Pallavi Ghildiyal
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
| | - Alexey Yumashev
- Department of Prosthetic Dentistry, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Ahmed Elawady
- College of technical engineering, the Islamic University, Najaf, Iraq
- College of technical engineering, the Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq
- College of technical engineering, the Islamic University of Babylon, Babylon, Iraq
| | - Sahel Sarabandi
- Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
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Barbosa IG, Miranda AS, Berk M, Teixeira AL. The involvement of the microbiota-gut-brain axis in the pathophysiology of mood disorders and therapeutic implications. Expert Rev Neurother 2025; 25:85-99. [PMID: 39630000 DOI: 10.1080/14737175.2024.2438646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 12/03/2024] [Indexed: 12/10/2024]
Abstract
INTRODUCTION There is a growing body of evidence implicating gut-brain axis dysfunction in the pathophysiology of mood disorders. Accordingly, gut microbiota has become a promising target for the development of biomarkers and novel therapeutics for bipolar and depressive disorders. AREAS COVERED We describe the observed changes in the gut microbiota of patients with mood disorders and discuss the available studies assessing microbiota-based strategies for their treatment. EXPERT OPINION Microbiota-targeted interventions, such as symbiotics, prebiotics, paraprobiotics, and fecal microbiota transplants seem to attenuate the severity of depressive symptoms. The available results must be seen as preliminary and need to be replicated and/or confirmed in larger and independent studies, also considering the pathophysiological and clinical heterogeneity of mood disorders.
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Affiliation(s)
- Izabela G Barbosa
- Departamento de Psiquiatria, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brasil
- Programa de Pós-Graduação em Neurociências, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
- Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), MG, Brasil
| | - Aline S Miranda
- Programa de Pós-Graduação em Neurociências, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
- Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), MG, Brasil
- Laboratório de Neurobiologia, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - Michael Berk
- IMPACT- the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, Australia
| | - Antonio L Teixeira
- Neuropsychiatry Division, The Biggs Institute for Alzheimer's & Neurodegenerative Diseases, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
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El Mouzan M, Alabdulkarim H, Kambal M, Alshammary N, Alanazi R, Ahamed S, Alhamid N, Al Sarkhy A, Alzahrani A, Assiri A. The outcome of functional constipation in Saudi children. Turk J Pediatr 2024; 66:713-718. [PMID: 39807733 DOI: 10.24953/turkjpediatr.2024.5286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 11/10/2024] [Indexed: 01/16/2025]
Abstract
BACKGROUND Understanding the outcome of functional constipation (FC) for both patients and physicians is essential, yet it has been infrequently reported worldwide. The objective of this report was to update the outcomes of FC in Saudi children. METHODS Clinical data including age, sex, response to management, duration of follow up, and type of management were collected from the notes of each clinic visits and phone call follow-ups. RESULTS The study included 268 children followed up for a 7 year duration. The median age of onset was 4 (0.1 to 13) years, and 123/268 (46%) were male. There was an increasing recovery rate with increasing duration of follow up with an overall recovery rate of 79%. There was no significant association between recovery and age at onset (p=0.0860) or duration of constipation (P=0.124). Management by pediatric gastroenterologists did not increase rate of recovery (81% vs. 77%, p=0.432) or being cured (47% vs. 36%, p=0.108) significantly. According to the parents of children who recovered, diet in association with polyethylene glycol (PEG) and toilet training were most helpful. Poor diet and nonadherence to medications were the most common causes of lack of recovery. CONCLUSIONS The higher rates of recovery in this Middle Eastern childhood population than other populations are possibly related to cultural characteristics. The parents' views support the importance of diet associated with other modalities as important parts of management. Further research is needed to identify correctable causes of nonadherence to treatment to improve recovery.
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Affiliation(s)
- Mohammad El Mouzan
- Gastroenterology Division, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Hayfa Alabdulkarim
- Gastroenterology Division, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Mohammed Kambal
- Gastroenterology Division, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Nawaf Alshammary
- Gastroenterology Division, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Rehab Alanazi
- Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Shaffi Ahamed
- Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Nouf Alhamid
- Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Ahmed Al Sarkhy
- Gastroenterology Division, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Alhanouf Alzahrani
- Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Asaad Assiri
- Gastroenterology Division, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
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Gao JW, Liu YD, Jin MX. Intestinal epithelial glycocalyx and intestinal disease. Shijie Huaren Xiaohua Zazhi 2024; 32:887-896. [DOI: 10.11569/wcjd.v32.i12.887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 11/08/2024] [Accepted: 12/17/2024] [Indexed: 12/28/2024] Open
Abstract
With the continuous research on glycobiology, more and more diseases are found to be associated with the glycocalyx. Glycocalyx can be categorized as endothelial glycocalyx and epithelial glycocalyx. Past studies mostly target endothelial glycocalyx, and this review focuses on the structure and function of intestinal epithelial glycocalyx, its degradation mechanism and biological relevance to different diseases of the intestinal tract, as well as the targeted delivery of drugs to organs by nanoparticle libraries mimicking the glycocalyx, in order to provide a theoretical basis for the study of potential diagnostic markers and therapeutic targets of intestinal epithelial glycocalyx in intestinal diseases.
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Affiliation(s)
- Jian-Wei Gao
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Yan-Di Liu
- Department of Gastroenterology, Tianjin People's Hospital, Tianjin 300071, China
| | - Ming-Xing Jin
- Department of Gastroenterology, Tianjin People's Hospital, Tianjin 300071, China
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Alshehri TK, Alsharif MNS, Asiri LAA, Mukharrib MS, Alzahrani MA. Prevalence and Associated Factors of Irritable Bowel Syndrome among Medical Students at King Khalid University. Ann Afr Med 2024; 24:01244624-990000000-00084. [PMID: 39710606 PMCID: PMC11837827 DOI: 10.4103/aam.aam_14_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2019] [Revised: 06/13/2020] [Accepted: 08/18/2020] [Indexed: 12/24/2024] Open
Abstract
BACKGROUND The stressful life of medical students might induce or exacerbate irritable bowel syndrome (IBS) symptoms. OBJECTIVES The purpose of this study was to determine the prevalence and related factors of IBS among medical students at King Khalid University (KKU), Saudi Arabia. MATERIALS AND METHODS A descriptive cross-sectional study was conducted among medical students at the KKU. The data collection period was from January to February 2018. Stratified sampling technique was used that included medical students from the second to the sixth year, using self-administered questionnaires contain socio-demographics, medical history, Rome criteria IV, and a personality scale of manifest anxiety. RESULTS The intended participants were 400 medical students (100%) with 363 (90%) respondents. The mean age was 22 ± 1.6 years; there were 52.9% males and 47.1% females. The prevalence rate of IBS according to the Rome IV criteria was 10.7%. Regarding diagnostic criteria for IBS subtypes, 23.1% represented for both IBS with predominant constipation and IBS with predominant diarrhea, IBS with mixed bowel habits, both diarrhea and constipation, are the higher percentage (43.6%), and IBS unclassified subtype represented by 10.3%. Chi-square test showed high correlation between age and smoking and body mass index (P = 0.04 and 0.05, respectively). Further, there is a significant relationship between IBS and anxiety level (P = 0.04). No gender difference was noted. CONCLUSION The prevalence of IBS among medical students at KKU was highest in the age group of 21-23 years, who were nonsmokers, and who had a relatively high grade point average. We did not find a gender difference. Compared to non-IBS students, the anxiety level of the students with IBS was dramatically higher.
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50
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Wan X, Wang L, Wang Z, Wan C. Toll-like receptor 4 plays a vital role in irritable bowel syndrome: a scoping review. Front Immunol 2024; 15:1490653. [PMID: 39749341 PMCID: PMC11693509 DOI: 10.3389/fimmu.2024.1490653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 12/02/2024] [Indexed: 01/04/2025] Open
Abstract
Background Irritable bowel syndrome (IBS) is a common gastrointestinal disease. Recently, an increasing number of studies have shown that Toll-like receptor 4 (TLR4), widely distributed on the surface of a variety of epithelial cells (ECs) and immune sentinel cells in the gut, plays a vital role in developing IBS. Objectives We sought to synthesize the existing literature on TLR4 in IBS and inform further study. Methods We conducted a systematic search of the PubMed, Embase (Ovid), Scopus, Web of Science, MEDLINE, and Cochrane Library databases on June 8, 2024, and screened relevant literature. Critical information was extracted, including clinical significance, relevant molecular mechanisms, and therapeutic approaches targeting TLR4 and its pathways. Results Clinical data showed that aberrant TLR4 expression is associated with clinical manifestations such as pain and diarrhea in IBS. Aberrant expression of TLR4 is involved in pathological processes such as intestinal inflammation, barrier damage, visceral sensitization, and dysbiosis, which may be related to TLR4, NF-κB, pro-inflammatory effects, and CRF. Several studies have shown that many promising therapeutic options (i.e., acupuncture, herbs, probiotics, hormones, etc.) have been able to improve intestinal inflammation, visceral sensitization, intestinal barrier function, intestinal flora, defecation abnormalities, and depression by inhibiting TLR4 expression and related pathways. Conclusion TLR4 plays a crucial role in the development of IBS. Many promising therapeutic approaches alleviate IBS through TLR4 and its pathways. Strategies for targeting TLR4 in the future may provide new ideas for treating IBS.
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Affiliation(s)
- Xuemeng Wan
- Department of Pediatrics, West China Second University Hospital of Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, China
- National Health Commission Key Laboratory of Chronobiology, Sichuan University, Chengdu, China
| | - Liyuan Wang
- Department of Pediatrics, West China Second University Hospital of Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, China
| | - Zhiling Wang
- Department of Pediatrics, West China Second University Hospital of Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, China
- National Health Commission Key Laboratory of Chronobiology, Sichuan University, Chengdu, China
| | - Chaomin Wan
- Department of Pediatrics, West China Second University Hospital of Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, China
- National Health Commission Key Laboratory of Chronobiology, Sichuan University, Chengdu, China
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