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Hajiani S, Tajabadi Ebrahimi M, Sadeghi A, Zarrabi Ahrabi N, Yadegar A. The impact of a multi-species probiotic supplementation on clinical symptoms and biochemical factors in patients with irritable bowel syndrome: a randomised controlled trial. Arch Physiol Biochem 2025:1-11. [PMID: 40392916 DOI: 10.1080/13813455.2025.2507749] [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: 12/23/2024] [Revised: 02/11/2025] [Accepted: 05/12/2025] [Indexed: 05/22/2025]
Abstract
Background: Intestinal inflammation and oxidative stress contribute to the pathophysiology of irritable bowel syndrome (IBS). This clinical trial investigated the effects of a probiotic supplementation on symptom severity and quality of life (QOL) in IBS patients. Methods: Forty-six IBS patients were randomised to receive either a multi-species probiotic or placebo for 8 weeks. Clinical symptoms were evaluated using the IBS Severity Scoring System (IBS-SSS) and IBS QOL questionnaire. Serum levels of IFN-γ, IL-1β, IL-10, IL-6, malondialdehyde (MDA), total antioxidant capacity (TAC), and nitric oxide (NO) were measured before and after the intervention. Results: After 8 weeks, the probiotic group showed significant improvements in QOL scores, and reductions in IBS-SSS and MDA levels compared to placebo group. TAC levels were significantly higher in probiotic group. However, no significant differences were observed in cytokine or NO levels. Conclusions: This multi-species probiotic supplement was safe and effective in reducing symptom severity and improved QOL of IBS patients.
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Affiliation(s)
- Shirin Hajiani
- Department of Biology, Faculty of Sciences, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Maryam Tajabadi Ebrahimi
- Department of Biology, Faculty of Sciences, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nakisa Zarrabi Ahrabi
- Department of Biology, Faculty of Sciences, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Nasab SJ, Feizi A, Hajihashemi P, Entezari MH, Sharma M, Adibi P, Bagherniya M. Effects of Spirulina (Arthrospira) platensis supplementation on intestinal permeability, antioxidant and inflammatory markers, quality of life and disease severity in patients with constipated-predominant irritable bowel syndrome: a randomized double‑blind, placebo‑controlled trial. Nutr J 2025; 24:64. [PMID: 40259354 PMCID: PMC12013150 DOI: 10.1186/s12937-025-01132-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Accepted: 04/12/2025] [Indexed: 04/23/2025] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a chronic, functional gastrointestinal disorder (FGID) which is characterized by chronic pain related to defecation and alteration in GI motility. Recent findings indicated that intestinal barrier dysfunction, hyperpermeability, oxidative stress, and inflammation play a role in IBS pathogenesis. Considering the antioxidant properties of Spirulina (Arthrospira) platensis (SP), this study aimed to investigate the effect of SP supplementation on Quality of life (QoL), disease severity, antioxidant capacity, oxidative stress index and intestinal permeability in constipation-dominant IBS (IBS-C) patients. METHODS This study was a parallel randomized, double-blind, placebo-controlled clinical trial involving 60 IBS-C patients aged 18-50 years. The patients were given either 1 g SP (two capsules/day; each capsule contained 500 mg of SP) or placebo for 12 weeks. IBS-QoL, IBS-Severity system score (IBS-SSS), plasma total antioxidant capacity (TAC), malondialdehyde (MDA), and zonulin levels were measured at baseline and the end of the intervention. Univariate comparison and intention-to-treat (ITT) were used for analysis. RESULTS SP supplementation compared to placebo resulted in a significant increase in QoL score (7.05 ± 2.02 vs. - 1.57 ± 2.49; p = 0.008), TAC (145.27 ± 30.77 vs. -54.90 ± 45.72; p < 0.001) and decrease in IBS-SSS (-32.17 ± 8.96 vs. 1.07 ± 8.49; p = 0.002), MDA level (- 11.61 ± 2.57 vs. - 2.00 ± 2.24; p < 0.001) and zonulin level (- 0.22 ± 0.05 vs. 0.12 ± 0.07; p = 0.001). These results remained significant after adjusting for baseline values. CONCLUSIONS SP supplementation demonstrated a promising effect in the management of IBS. However, larger trials with a dose-dependent approach in IBS-C and other subtypes of IBS are warranted. TRIAL REGISTRATION The study protocol was approved by the ethical committee at the Isfahan University of Medical Sciences (Registration No. IR.MUI. RESEARCH REC.1401.370) and registered online at http://www.IRCT.ir (code: IRCT20140208016529N8, approved date 25.04.2023).
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Affiliation(s)
- Saeede Jafari Nasab
- Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Awat Feizi
- Department of Epidemiology and Biostatistics, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Parisa Hajihashemi
- Isfahan Gastroenterology and Hepatology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad-Hassan Entezari
- Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Manoj Sharma
- Department of Social & Behavioral Health, School of Public Health, University of Nevada, Las Vegas, NV, USA
| | - Peyman Adibi
- Isfahan Gastroenterology and Hepatology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Bagherniya
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.
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Guo Y, Wang L, Huang JQ, Lu MW, Yang SH. Valorization of Pomegranate Peel: Mechanisms and Clinical Applications in Irritable Bowel Syndrome Management. Int J Mol Sci 2025; 26:3530. [PMID: 40332037 PMCID: PMC12026873 DOI: 10.3390/ijms26083530] [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: 03/01/2025] [Revised: 04/04/2025] [Accepted: 04/06/2025] [Indexed: 05/08/2025] Open
Abstract
Current disposal methods for pomegranate peel (PP) waste are inadequate, resulting in environmental pollution. Given PP's therapeutic potential in alleviating irritable bowel syndrome (IBS), elucidating its bioactive mechanisms is critical to guide its development into dietary supplements and promote sustainable recycling. In this study, bioinformatics and network analysis were employed to identify active compounds, key targets, and signaling pathways associated with PP's therapeutic effects. We identified 39 bioactive compounds (primarily polyphenols) and 106 key targets linked to IBS. Network analyses revealed that PP polyphenols mitigate oxidative stress and inflammation, modulate estrogen receptors to enhance gastrointestinal motility, and regulate ferroptosis. These findings underscore PP's potential as a therapeutic agent for IBS and provide a framework for repurposing food-processing byproducts.
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Affiliation(s)
- Yu Guo
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, China;
- School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China;
| | - Lu Wang
- Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Sciences, Universidade de Vigo, 32004 Ourense, Spain;
| | - Jun-Qing Huang
- School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China;
| | - Mu-Wen Lu
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou 510632, China
| | - Song-Hong Yang
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, China;
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Gao Y, Chen C, Huang X, Liu Y, Zhou Z, Pan Y. Omentin-1, a Protective Adipokine for Irritable Bowel Syndrome. J Inflamm Res 2025; 18:1689-1701. [PMID: 39925934 PMCID: PMC11806724 DOI: 10.2147/jir.s499613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Accepted: 01/25/2025] [Indexed: 02/11/2025] Open
Abstract
Introduction Irritable bowel syndrome (IBS) is characterized by patients' high level of suffering. There is increasing evidence for involvement of the immune system in this disease. Adipokines have been reported to be critical immunoregulators in many clinical conditions, including gastrointestinal (GI) inflammatory diseases. Our study aimed to investigate associations of omentin-1 (a newly discovered adipokine) with IBS. Methods In the current study, serum levels of omentin-1 were measured in 209 patients with IBS (including three subtypes) and 188 healthy controls by enzyme-linked immunosorbent assay (ELISA). The somatic symptoms of IBS were determined by the 5-item IBS symptoms severity score (IBS-SSS), quality of life (QOL) by 34-item IBS-QOL questionnaire, and psychological disorders by Patient Health Questionnaire (PHQ-9), Hospital Anxiety and Depression Scale (HADS), Visceral Sensitivity Index (VSI). Therapeutic effect of omentin-1 for IBS was investigated in a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced IBS mouse model. Results We found that serum levels of omentin-1 were significantly decreased in patients with the diarrhea-predominant IBS (IBS-D) subtype (not the constipation or alternating subtype) compared to those in healthy subjects. Patients with lower serum omentin-1 levels suffered from higher severity of somatic symptoms (abdominal pain and distention, flatulence, rumbling), lower QOL, and worse psychological status. In a one-year follow-up, serum omentin-1 levels showed potential to reflect the disease progression. Additionally, lower omentin-1 levels were found to be accompanied with higher levels of serum pro-inflammatory cytokine concentrations in patients with IBS-D. Supplement of omentin-1 was protective against visceral hypersensitivity and mucosal inflammation in an IBS mouse model. Discussion Our findings highlight the potential value of serum omentin-1 levels as an innovative biomarker in IBS, emphasizing its significance in improving clinical treatment and management of the disease.
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Affiliation(s)
- Yanping Gao
- Department of Gastroenterology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
| | - Chen Chen
- Department of Gastroenterology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
| | - Xijing Huang
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
| | - Ya Liu
- Department of Gastroenterology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
| | - Zhou Zhou
- Department of Gastroenterology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
| | - Yan Pan
- Department of Gastroenterology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
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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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García Mansilla MJ, Rodríguez Sojo MJ, Lista AR, Ayala Mosqueda CV, Ruiz Malagón AJ, Gálvez J, Rodríguez Nogales A, Rodríguez Sánchez MJ. Exploring Gut Microbiota Imbalance in Irritable Bowel Syndrome: Potential Therapeutic Effects of Probiotics and Their Metabolites. Nutrients 2024; 17:155. [PMID: 39796588 PMCID: PMC11723002 DOI: 10.3390/nu17010155] [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: 12/04/2024] [Revised: 12/24/2024] [Accepted: 12/26/2024] [Indexed: 01/13/2025] Open
Abstract
Irritable bowel syndrome is a common functional gastrointestinal disorder characterized by recurrent abdominal discomfort, bloating, cramping, flatulence, and changes in bowel movements. The pathophysiology of IBS involves a complex interaction between motor, sensory, microbiological, immunological, and psychological factors. Diversity, stability, and metabolic activity of the gut microbiota are frequently altered in IBS, thus leading to a situation of gut dysbiosis. Therefore, the use of probiotics and probiotic-derived metabolites may be helpful in balancing the gut microbiota and alleviating irritable bowel syndrome symptoms. This review aimed to report and consolidate recent progress in understanding the role of gut dysbiosis in the pathophysiology of IBS, as well as the current studies that have focused on the use of probiotics and their metabolites, providing a foundation for their potential beneficial effects as a complementary and alternative therapeutic strategy for this condition due to the current absence of effective and safe treatments.
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Affiliation(s)
- María José García Mansilla
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
| | - María Jesús Rodríguez Sojo
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
| | - Andrea Roxana Lista
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
| | | | - Antonio Jesús Ruiz Malagón
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29590 Málaga, Spain
| | - Julio Gálvez
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
- CIBER de Enfermedades Hepáticas y Digestivas (CIBER-EHD), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Alba Rodríguez Nogales
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
| | - María José Rodríguez Sánchez
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
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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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Zhang Y, Huang S, Zhang S, Hao Z, Shen J. Pomegranate Peel Extract Mitigates Diarrhea-Predominant Irritable Bowel Syndromes via MAPK and NF-κB Pathway Modulation in Rats. Nutrients 2024; 16:3854. [PMID: 39599640 PMCID: PMC11597445 DOI: 10.3390/nu16223854] [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: 10/10/2024] [Revised: 10/26/2024] [Accepted: 10/28/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common chronic functional gastrointestinal disorder that causes diarrheal and intestinal barrier disruptions. Although pomegranate peel extract (PPE) has been reported for the treatment of diarrheal and intestinal inflammation, its effectiveness and mechanisms specifically for the treatment of IBS-D remain unknown. OBJECTIVES This study aimed to explore the therapeutic effect of PPE on IBS-D and elucidate its underlying mechanisms. METHODS A high-fat diet, restraint stress, and senna gavage were combined to establish a rat model mimicking IBS-D, to evaluate the therapeutic effects of PPE. Network pharmacology analysis, serum medicinal chemistry, and transcriptomics were employed to investigate potential downstream signaling pathways. Findings were further validated through molecular docking and Western blot analysis. RESULTS The findings revealed that PPE significantly improved the symptoms of IBS-D, ameliorated intestinal inflammation, and promoted intestinal barrier function. The target genes in the MAPK and NF-κB signaling pathways were significantly enriched and down-regulated. Molecular docking and Western blot assays were performed to verify that PPE had a high affinity for the protein candidates in these pathways, and significantly down-regulated the expression of p-IκB, p-p65, p-JNK, p-p38, and p-ERK1/2. CONCLUSIONS The present study is the first to demonstrate that PPE alleviates diarrheal and intestinal damage in IBS-D, potentially by inhibiting MAPK and NF-κB signaling pathways. These findings suggest that PPE may provide a novel therapeutic option for IBS-D.
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Affiliation(s)
- Yannan Zhang
- National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; (Y.Z.); (S.H.); (S.Z.)
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China
| | - Sijuan Huang
- National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; (Y.Z.); (S.H.); (S.Z.)
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China
| | - Shuai Zhang
- National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; (Y.Z.); (S.H.); (S.Z.)
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China
| | - Zhihui Hao
- National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; (Y.Z.); (S.H.); (S.Z.)
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China
| | - Jianzhong Shen
- National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; (Y.Z.); (S.H.); (S.Z.)
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China
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Passacatini LC, Ilari S, Nucera S, Scarano F, Macrì R, Caminiti R, Serra M, Oppedisano F, Maiuolo J, Palma E, Malafoglia V, Tomino C, Fini M, Mollace V, Muscoli C. Multiple Aspects of Irritable Bowel Syndrome and the Role of the Immune System: An Overview of Systematic Reviews with a Focus on Polyphenols. Int J Mol Sci 2024; 25:11993. [PMID: 39596064 PMCID: PMC11593788 DOI: 10.3390/ijms252211993] [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: 10/18/2024] [Revised: 11/05/2024] [Accepted: 11/06/2024] [Indexed: 11/28/2024] Open
Abstract
Irritable bowel syndrome (IBS) is a complex and often debilitating condition that significantly impacts the gastrointestinal system and the overall quality of life of those affected. IBS is characterized by a variety of distressing symptoms, including cramping, abdominal pain, and irregular bowel movements, underlined by an intricate interplay of immune system dysfunction in its pathology. Numerous studies highlight an increased cellular immune response, with elevated levels of proinflammatory cytokines, mucosal alterations due to immune imbalance, and visceral hypersensitivity. Notably, studies indicate increased levels of proinflammatory cytokines, immune imbalances that lead to mucosal changes, and heightened visceral sensitivity. The roles of effector and regulatory T cells are particularly intriguing, as their modification appears to amplify inflammation and may even contribute to autoimmune disorders. This overview of systematic reviews explores the connections between IBS and immune responses, with a focus on immune cell alterations and proliferation of lymphocytes and mast cells in affected individuals. Furthermore, we explore various aspects of IBS management, including its pharmacological approaches. A systematic search of PubMed and Web of Science yielded 676 articles, which were ultimately narrowed down to 9 key studies that met our inclusion criteria. These studies collectively underscore the activation of the immune system with the degranulation of the mast cells in patients with IBS, where the release of inflammatory mediators can compromise intestinal permeability, exacerbating symptoms further. Additionally, we examine the multifaceted management strategies for IBS, emphasizing the potential therapeutic benefits of dietary polyphenols as antioxidants. The present study aims to enhance our understanding of IBS and offer insights into more effective treatment strategies for this challenging condition.
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Affiliation(s)
| | - Sara Ilari
- IRCCS San Raffaele Roma, 00166 Rome, Italy; (L.C.P.); (V.M.); (C.T.); (M.F.)
| | - Saverio Nucera
- Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy; (S.N.); (F.S.); (R.M.); (R.C.); (M.S.); (F.O.); (J.M.); (E.P.); (V.M.)
| | - Federica Scarano
- Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy; (S.N.); (F.S.); (R.M.); (R.C.); (M.S.); (F.O.); (J.M.); (E.P.); (V.M.)
| | - Roberta Macrì
- Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy; (S.N.); (F.S.); (R.M.); (R.C.); (M.S.); (F.O.); (J.M.); (E.P.); (V.M.)
| | - Rosamaria Caminiti
- Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy; (S.N.); (F.S.); (R.M.); (R.C.); (M.S.); (F.O.); (J.M.); (E.P.); (V.M.)
| | - Maria Serra
- Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy; (S.N.); (F.S.); (R.M.); (R.C.); (M.S.); (F.O.); (J.M.); (E.P.); (V.M.)
| | - Francesca Oppedisano
- Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy; (S.N.); (F.S.); (R.M.); (R.C.); (M.S.); (F.O.); (J.M.); (E.P.); (V.M.)
| | - Jessica Maiuolo
- Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy; (S.N.); (F.S.); (R.M.); (R.C.); (M.S.); (F.O.); (J.M.); (E.P.); (V.M.)
| | - Ernesto Palma
- Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy; (S.N.); (F.S.); (R.M.); (R.C.); (M.S.); (F.O.); (J.M.); (E.P.); (V.M.)
| | | | - Carlo Tomino
- IRCCS San Raffaele Roma, 00166 Rome, Italy; (L.C.P.); (V.M.); (C.T.); (M.F.)
| | - Massimo Fini
- IRCCS San Raffaele Roma, 00166 Rome, Italy; (L.C.P.); (V.M.); (C.T.); (M.F.)
| | - Vincenzo Mollace
- Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy; (S.N.); (F.S.); (R.M.); (R.C.); (M.S.); (F.O.); (J.M.); (E.P.); (V.M.)
| | - Carolina Muscoli
- Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy; (S.N.); (F.S.); (R.M.); (R.C.); (M.S.); (F.O.); (J.M.); (E.P.); (V.M.)
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10
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Castiglione R, Bertino G, Vicari BO, Rizzotto A, Sidoti G, D’Agati P, Salemi M, Malaguarnera G, Vicari E. Inflammatory Prostatitis Plus IBS-D Subtype and Correlation with Immunomodulating Agent Imbalance in Seminal Plasma: Novel Combined Treatment. Diseases 2024; 12:260. [PMID: 39452503 PMCID: PMC11508116 DOI: 10.3390/diseases12100260] [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: 07/29/2024] [Revised: 10/12/2024] [Accepted: 10/15/2024] [Indexed: 10/26/2024] Open
Abstract
We recently demonstrated the effectiveness of long-term treatment with rifaximin and the probiotic DSF (De Simone formulation) in improving urogenital and gastrointestinal symptoms in patients with both chronic inflammatory prostatitis (IIIa prostatitis) and diarrhea-predominant irritable bowel syndrome (IBS-D), relative to patients with IBS-D alone. Because the low-grade inflammation of the intestine and prostate may be one of the reasons for co-developing both IIIa prostatitis and IBS-D, we designed the present study to once again evaluate the efficacy of combined rifaximin and DSF treatment in patients affected by IIIa prostatitis plus IBS-D, but we also measured seminal plasma pro-inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines before and after treatment. Methods: We consecutively enrolled 124 patients with IIIa prostatitis and IBS-D (diagnosed using the Rome III criteria). Patients were randomized into two groups: group A (n = 64) was treated with rifaximin (seven days per month for three months) followed by DSF, and group B (n = 60) was treated with a placebo. By the end of the intervention, 68.7% and 62.5% of patients from group A reported improved NIH-CPSI (National Institute of Health's Chronic Prostatitis Symptom Index) and IBS-SSS (Irritable Bowel Syndrome Severity Scoring System) scores, respectively, compared to only 3.3% and 5% of the placebo group. Group A patients also had significantly lower mean seminal plasma levels of IL-6 (11.3 vs. 32.4 pg/mL) and significantly higher mean levels of IL-10 (7.9 vs. 4.4 pg/mL) relative to baseline, whereas the levels of IL-6 and IL-10 did not change in the placebo group. Conclusions: The combined treatment with rifaximin and DSF appears to represent the optimal approach for addressing a syndrome such as irritable bowel syndrome (IBS-D plus), which frequently co-occurs with prostatitis (IIIa prostatitis). This approach is particularly beneficial in cases where the symptoms are not always clearly delineated, the etiology is multifactorial, and the diagnosis is multilevel.
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Affiliation(s)
- Roberto Castiglione
- Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Gaetano Bertino
- Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | | | - Agostino Rizzotto
- Center of Rare Diseases, Policlinico Catania, University of Catania, 95100 Catania, Italy
| | - Giuseppe Sidoti
- Simple Departmental Operating Unit, Internal Medicine Ambulatory Andrology & Endocrinology, ARNAS-Garibaldi, 95123 Catania, Italy
| | - Placido D’Agati
- Department “GF Ingrassia” Hygiene and Public Health, University of Catania, 95123 Catania, Italy
| | | | - Giulia Malaguarnera
- Research Center “The Great Senescence”, University of Catania, 95100 Catania, Italy
| | - Enzo Vicari
- Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
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11
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Huang Y, Zheng E, Hu M, Yang X, Lan Q, Yu Y, Xu B. The impact of depression-mediated gut microbiota composition on Irritable Bowel Syndrome: A Mendelian study. J Affect Disord 2024; 360:15-25. [PMID: 38801922 DOI: 10.1016/j.jad.2024.05.119] [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: 04/10/2024] [Revised: 05/22/2024] [Accepted: 05/23/2024] [Indexed: 05/29/2024]
Abstract
OBJECTIVE This study uses a two-sample Mendelian randomization (MR) analysis to delineate the causal influence of gut microbiota on the occurrence of irritable bowel syndrome (IBS), concurrently assessing the potential mediating function of depression within this framework. METHODS Several two-sample MR methods were used to assess the causal repercussions of gut microbiota on the onset of both IBS and depression. Following this, gut microbiota and depression, which demonstrated notable causal associations, were integrated as exposure variables in a multivariable Mendelian randomization (MVMR) framework to construct a model encompassing gut microbiota, depression, and IBS. Mediation effects were assessed by examining the indirect pathway of gut microbiota → depression → IBS. RESULTS Two-sample MR analysis unveiled a statistically significant causal association (P < 0.05) between specific bacterial group within the gut microbiota, notably p_Actinobacteria(OR = 0.829225), c_Clostridia(OR = 0.798897), s_Desulfovibrio_piger(OR = 1.163912), g_Streptococcus(OR = 1.132735), c_Actinobacteria(OR = 0.829224), and the onset of IBS. In the MVMR analysis, the relationship between depression and IBS was significant across Model 3, Model 7, Model 8, and Model 13 (P < 0.05). Assessment of mediation effects revealed that c_Clostridia and o_Clostridiales indirectly impacted IBS through depression, with masking effect ratios of 168.46 % and 168.44 %, respectively. CONCLUSION These findings underscore a resilient causal association between the composition of gut microbiota and the initiation of IBS. Furthermore, depression serves as a mediator for particular groups of gut bacteria, thereby contributing to the development of IBS. These observations imply that interventions targeting mental health may potentially alleviate the risk of IBS onset attributable to adverse configurations of gut microbiota.
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Affiliation(s)
- Yi Huang
- Department of General Surgery, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou 325000, Zhejiang, China
| | - Endian Zheng
- Department of Gastroenterology, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou 325000, Zhejiang, China
| | - Mei Hu
- Postgraduate training base Alliance of Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou 325000, Zhejiang, China
| | - Xinxin Yang
- Department of Infectious Diseases, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou 325000, Zhejiang, China
| | - Qiaoli Lan
- Department of Gastroenterology, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou 325000, Zhejiang, China
| | - Yingcong Yu
- Department of Gastroenterology, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou 325000, Zhejiang, China.
| | - Beibei Xu
- Department of Gastroenterology, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou 325000, Zhejiang, China.
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12
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JohnBritto JS, Di Ciaula A, Noto A, Cassano V, Sciacqua A, Khalil M, Portincasa P, Bonfrate L. Gender-specific insights into the irritable bowel syndrome pathophysiology. Focus on gut dysbiosis and permeability. Eur J Intern Med 2024; 125:10-18. [PMID: 38467533 DOI: 10.1016/j.ejim.2024.03.011] [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: 02/08/2024] [Accepted: 03/05/2024] [Indexed: 03/13/2024]
Abstract
Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder involving the brain-gut interaction. IBS is characterized by persistent abdominal pain and changes in bowel habits. IBS exerts significant impacts on quality of life and imposes huge economic costs. Global epidemiological data reveal variations in IBS prevalence, both globally and between genders, necessitating comprehensive studies to uncover potential societal and cultural influences. While the exact pathophysiology of IBS remains incompletely understood, the mechanism involves a dysregulation of the brain-gut axis, leading to disturbed intestinal motility, local inflammation, altered intestinal permeability, visceral sensitivity, and gut microbiota composition. We reviewed several gender-related pathophysiological aspects of IBS pathophysiology, by focusing on gut dysbiosis and intestinal permeability. This perspective paves the way to personalized and multidimensional clinical management of individuals with IBS.
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Affiliation(s)
- Jerlin Stephy JohnBritto
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Jonian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
| | - Agostino Di Ciaula
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Jonian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
| | - Antonino Noto
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Jonian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
| | - Velia Cassano
- Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy
| | - Angela Sciacqua
- Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy
| | - Mohamad Khalil
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Jonian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
| | - Piero Portincasa
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Jonian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy.
| | - Leonilde Bonfrate
- Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Jonian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
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13
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Hansen AS, Rask CU, Kallesøe KH. Inflammatory Markers in Children and Adolescents with Functional Somatic Disorders: A Systematic Review. CHILDREN (BASEL, SWITZERLAND) 2024; 11:549. [PMID: 38790544 PMCID: PMC11119612 DOI: 10.3390/children11050549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 04/28/2024] [Accepted: 05/02/2024] [Indexed: 05/26/2024]
Abstract
Functional somatic disorders (FSDs) are common in children and adolescents. Recent findings suggest that low-grade inflammation has a role in the development and maintenance of pediatric FSDs. This systematic review included studies with original data on systemic inflammatory markers in children and adolescents with an FSD compared to individuals without an FSD. The literature search identified 1374 articles. After assessment, a total of 15 studies met the inclusion criteria. In total, 41 serum or plasma cytokines were assayed in a population of 696 children and adolescents. Altered cytokine levels in patients with FSDs were reported in 12 studies, whereas three studies found no significant differences when comparing patients with FSDs and controls. The cytokine levels were significantly elevated in nine studies (i.e., IL-2, IL-6, IL-8, IL-12 (p70), CRP, hsCRP, IP-10, MCP-1, sTIM-3, sCD25 and TNF-α). The findings indicate that inflammatory response may have a role in the pathophysiology of pediatric FSDs. However, the included studies showed limited quality with potential risk of bias, small study populations and a narrow spectrum of included FSDs, which limits the generalizability of the results. To further explore the potential link between inflammatory markers and pediatric FSDs, future research using a longitudinal study design is recommended.
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Affiliation(s)
- Anne Sofie Hansen
- Department of Child and Adolescent Psychiatry, Aalborg University Hospital, 9000 Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark
| | - Charlotte Ulrikka Rask
- Department of Child and Adolescent Psychiatry, Aarhus University Hospital Psychiatry, 8200 Aarhus N, Denmark; (C.U.R.); (K.H.K.)
- Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark
| | - Karen Hansen Kallesøe
- Department of Child and Adolescent Psychiatry, Aarhus University Hospital Psychiatry, 8200 Aarhus N, Denmark; (C.U.R.); (K.H.K.)
- Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark
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14
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Ji Q, Du F, Yu Y, Li Y. Exploring the clinical significance of miR-148 expression variations in distinct subtypes of irritable bowel syndrome. Ann Hum Genet 2024; 88:247-258. [PMID: 38161272 DOI: 10.1111/ahg.12543] [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: 07/27/2023] [Revised: 11/22/2023] [Accepted: 11/30/2023] [Indexed: 01/03/2024]
Abstract
Irritable bowel syndrome (IBS) belongs to chronic functional gastrointestinal diseases featured by abdominal pain and changes in bowel habits. This study aimed to investigate the clinical significance of serum miR-148 expression in different subtypes of IBS. We enrolled 86 IBS patients and 55 healthy controls. miR-148 expression levels were assessed in IBS patients classified into IBS-constipation (IBS-C), IBS-diarrhea (IBS-D), and IBS-mixed stool pattern (IBS-M) subtypes. Receiver-operating characteristic (ROC) curves were employed to evaluate the diagnostic potential of miR-148 in distinguishing among IBS subtypes. Additionally, we analyzed the correlation between miR-148 expression and clinical characteristics, including IBS symptom severity. miR-148 expression was highest in IBS-D (diarrhea) group, followed by IBS-M and IBS-C. With the exception of the IBS-C group, miR-148 expression was elevated in IBS patients compared to controls. ROC curve analysis demonstrated that serum miR-148 exhibited higher diagnostic accuracy for discriminating IBS-C and IBS-D than IBS-M. Correlation analysis revealed a positive relationship between serum miR-148 relative expression and IBS symptom severity system scores. Univariate logistic analysis indicated a positive association between miR-148 expression and IBS-D and a negative correlation with IBS-C. miR-148 expression exhibits differential patterns among IBS subtypes and holds a potential to distinguish IBS-C and IBS-D. Furthermore, miR-148 expression correlates with the severity of IBS symptoms.
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Affiliation(s)
- Qun Ji
- Department of General Practice, Inner Mongolia Baogang Hospital, Baotou, Inner Mongolia, China
| | - Fengxia Du
- Department of Hospital Infection Management, Inner Mongolia Baogang Hospital, Baotou, Inner Mongolia, China
| | - Yangyaxin Yu
- Department of General Practice, Baotou Jiuyuan District Hospital, Baotou, Inner Mongolia, China
| | - Ying Li
- Department of General Practice, Inner Mongolia Baogang Hospital, Baotou, Inner Mongolia, China
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15
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Wang Y, Kim SH, Klein ME, Chen J, Gu E, Smith S, Bortsov A, Slade GD, Zhang X, Nackley AG. A mouse model of chronic primary pain that integrates clinically relevant genetic vulnerability, stress, and minor injury. Sci Transl Med 2024; 16:eadj0395. [PMID: 38598615 DOI: 10.1126/scitranslmed.adj0395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 03/15/2024] [Indexed: 04/12/2024]
Abstract
Chronic primary pain conditions (CPPCs) affect over 100 million Americans, predominantly women. They remain ineffectively treated, in large part because of a lack of valid animal models with translational relevance. Here, we characterized a CPPC mouse model that integrated clinically relevant genetic (catechol-O-methyltransferase; COMT knockdown) and environmental (stress and injury) factors. Compared with wild-type mice, Comt+/- mice undergoing repeated swim stress and molar extraction surgery intervention exhibited pronounced multisite body pain and depressive-like behavior lasting >3 months. Comt+/- mice undergoing the intervention also exhibited enhanced activity of primary afferent nociceptors innervating hindpaw and low back sites and increased plasma concentrations of norepinephrine and pro-inflammatory cytokines interleukin-6 (IL-6) and IL-17A. The pain and depressive-like behavior were of greater magnitude and longer duration (≥12 months) in females versus males. Furthermore, increases in anxiety-like behavior and IL-6 were female-specific. The effect of COMT genotype × stress interactions on pain, IL-6, and IL-17A was validated in a cohort of 549 patients with CPPCs, demonstrating clinical relevance. Last, we assessed the predictive validity of the model for analgesic screening and found that it successfully predicted the lack of efficacy of minocycline and the CB2 agonist GW842166X, which were effective in spared nerve injury and complete Freund's adjuvant models, respectively, but failed in clinical trials. Yet, pain in the CPPC model was alleviated by the beta-3 adrenergic antagonist SR59230A. Thus, the CPPC mouse model reliably recapitulates clinically and biologically relevant features of CPPCs and may be implemented to test underlying mechanisms and find new therapeutics.
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Affiliation(s)
- Yaomin Wang
- Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Shin Hyung Kim
- Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, NC 27710, USA
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Marguerita E Klein
- Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Jiegen Chen
- Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Elizabeth Gu
- Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Shad Smith
- Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Andrey Bortsov
- Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Gary D Slade
- Center for Pain Research and Innovation, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Xin Zhang
- Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Andrea G Nackley
- Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, NC 27710, USA
- Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA
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16
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Wal A, Srivastava A, Verma N, Pandey SS, Tyagi S. The Role of Nutraceutical Supplements in the Treatment of Irritable Bowel Syndrome: A Mini Review. Curr Pediatr Rev 2024; 20:66-75. [PMID: 36593535 DOI: 10.2174/1573396319666230102121953] [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: 06/17/2022] [Revised: 10/17/2022] [Accepted: 11/23/2022] [Indexed: 01/04/2023]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a prolonged bowel illness that is generally stress-related and is characterized by a variety of gastrointestinal problems, the most prominent of which is chronic visceral abdominal discomfort. As a result, IBS typically impacts sufferers' standard of living, and it is typically associated with depression and anxiety symptoms. IBS medication is based mostly on symptom alleviation. However, no effective medicines have been discovered too far. As a result, it is essential to discover novel anti-IBS medications. OBJECTIVE The purpose of this brief review is to describe the existing research on nutraceutical supplements in irritable bowel syndrome management, including probiotics, prebiotics, symbiotics, herbal products, and dietary fibers. METHODS This review covered the relevant papers from the previous twenty years that were available in different journals such as Science Direct, Elsevier, NCBI, and Web of Science that were related to the role and function of nutraceuticals in Irritable Bowel Syndrome. RESULTS Nutraceutical substances have a variety of modes of action, including restoring the healthy microbiome, improving the function of the gastrointestinal barrier, immunomodulatory, antiinflammatory, and antinociceptive properties. According to the literature, these substances not only can improve irritable bowel syndrome symptomatology but also have an excellent long-term safety profile. CONCLUSION Irritable bowel syndrome is a prolonged bowel illness with a lot of gastrointestinal problems. The nutraceuticals treatment works as an anti-IBS intervention and enhances patient compliance with minimum side effects since patients take it better than pharmaceutical treatments.
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Affiliation(s)
- Ankita Wal
- Department of Pharmacy, Pranveer Singh Institute of Technology, UP, India
| | - Ashish Srivastava
- Department of Pharmacy, Pranveer Singh Institute of Technology, UP, India
| | - Neha Verma
- Department of Pharmacy, Pranveer Singh Institute of Technology, UP, India
| | - Shiv Shanker Pandey
- Department of Pharmacology, Tahira Institute of Medical Sciences, GIDA, Gorakhpur, UP, India
| | - Sachin Tyagi
- Department of Pharmacology, Bharat Institute of Technology, School of Pharmacy Meerut, UP, India
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Xia Y, Tan W, Yuan F, Lin M, Luo H. Luteolin Attenuates Oxidative Stress and Colonic Hypermobility in Water Avoidance Stress Rats by Activating the Nrf2 Signaling Pathway. Mol Nutr Food Res 2024; 68:e2300126. [PMID: 38037466 DOI: 10.1002/mnfr.202300126] [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: 03/05/2023] [Revised: 07/30/2023] [Indexed: 12/02/2023]
Abstract
SCOPE Irritable bowel syndrome (IBS) is an intestinal disorder, whose symptoms can be alleviated by certain dietary phytochemicals. This study explores the role and potential mechanisms of a natural flavonoid luteolin (LUT) in alleviating the excessive motility of colonic smooth muscles and reducing oxidative stress in IBS with diarrhea (IBS-D) rats. METHODS AND RESULTS LUT reduces excessive intestinal motility and lowers reactive oxygen species (ROS) levels in a water avoidance stress (WAS) rat model. Moreover, LUT increases the protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), activates the nuclear translocation of Nrf2, and greatly reduces the hydrogen peroxide (H2 O2 )-induced oxidative damage in intestinal epithelial cells. CONCLUSIONS LUT, a phyto-active component, protects against excessive intestinal motility and diarrhea by regulating the Nrf2 signaling pathway and effectively reduces oxidative stress damage in the colon.
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Affiliation(s)
- Yuan Xia
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
- Key Laboratory of Hubei Province for Digestive System Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Wei Tan
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
- Key Laboratory of Hubei Province for Digestive System Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Fangting Yuan
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
- Key Laboratory of Hubei Province for Digestive System Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Mengjuan Lin
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
- Key Laboratory of Hubei Province for Digestive System Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Hesheng Luo
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
- Key Laboratory of Hubei Province for Digestive System Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
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Benchabane S, Sour S, Zidi S, Hadjimi Z, Nabila L, Acheli D, Bouzenad A, Belguendouz H, Touil-Boukoffa C. Exploring the relationship between oxidative stress status and inflammatory markers during primary Sjögren's syndrome: A new approach for patient monitoring. Int J Immunopathol Pharmacol 2024; 38:3946320241263034. [PMID: 38901876 PMCID: PMC11191624 DOI: 10.1177/03946320241263034] [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: 02/14/2024] [Accepted: 05/31/2024] [Indexed: 06/22/2024] Open
Abstract
INTRODUCTION Primary Sjögren's syndrome (pSS) is a chronic inflammatory disease primarily affects exocrine glands dysfunction. Oxidative stress (OS) is a phenomenon occurring as a result of an imbalance between the generation of free radicals and antioxidant defense system. Hence, we aimed to establish the status of OS and inflammatory response according to the pSS disease activity index. In this context, we investigated malondialdehyde (MDA), and antioxidant enzymes during pSS. The possible association between MDA and nitric oxide (NO) levels and between MDA and some pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IL-33). METHODS The study has been conducted on 53 pSS patients. The antioxidant enzymes, represented by glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD), were estimated by a colorimetric activity kit. Whereas, MDA value was assessed by measuring thiobarbituric acid reactive substances. Moreover, pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IL-33) and NO were respectively quantified by enzyme-linked immunosorbent assays (ELISA) and the modified Griess. RESULTS Interestingly, we report a notable reduction in our pSS patients' antioxidant enzyme activity, while NO, MDA and proinflammatory cytokines values were significantly increased. pSS patients with higher disease activity had much stronger increases in NO and MDA levels. No significant difference was assessed in CRP level. Additionally, substantial significant correlations between plasmatic NO and MDA levels and between MDA, NO and IL-1β, IL-6, TNF-α cytokines were reported. However, no significant association was found between NO, MDA and IL-33 concentrations. CONCLUSION Collectively, our data showed altered oxidant-antioxidant balance in pSS patients. MDA, NO, IL-1β, IL-6, TNF-α seem to be good indicators in monitoring disease activity. Oxidative stress was closely related to inflammation in pSS. Exploiting this relationship might provide valuable indicators in the follow-up and prognosis of pSS with a potential therapeutic value.
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Affiliation(s)
- Sarah Benchabane
- Laboratory of Cellular and Molecular Biology (LBCM), Cytokines and NO Synthases Team, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), Algiers, Algeria
- Faculty of Natural Sciences and Life, Department of Biology, Saad Dahlab’s University of Blida, Blida, Algeria
| | - Souad Sour
- Faculty of Natural Sciences and Life, Department of Biology, Saad Dahlab’s University of Blida, Blida, Algeria
| | - Sourour Zidi
- Laboratory of Cellular and Molecular Biology (LBCM), Cytokines and NO Synthases Team, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), Algiers, Algeria
- Department of Natural Sciences, Guelma University, Guelma, Algeria
| | - Zohra Hadjimi
- Laboratory of Cellular and Molecular Biology (LBCM), Cytokines and NO Synthases Team, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), Algiers, Algeria
| | - Lyazidi Nabila
- Internal Medicine Department, Issad Hassani Hospital- Algiers 1 University of Medicine, Algiers, Algeria
| | - Dahbia Acheli
- Internal Medicine Department, Douera Hospital- Algiers 1 University of Medicine, Algiers, Algeria
| | - Amel Bouzenad
- Medical Biology Laboratory, Pasteur Institut- Algiers 1 University of Medicine, Algiers, Algeria
| | - Houda Belguendouz
- Laboratory of Cellular and Molecular Biology (LBCM), Cytokines and NO Synthases Team, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), Algiers, Algeria
| | - Chafia Touil-Boukoffa
- Laboratory of Cellular and Molecular Biology (LBCM), Cytokines and NO Synthases Team, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), Algiers, Algeria
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19
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Chen C, Beloqui A, Xu Y. Oral nanomedicine biointeractions in the gastrointestinal tract in health and disease. Adv Drug Deliv Rev 2023; 203:115117. [PMID: 37898337 DOI: 10.1016/j.addr.2023.115117] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 10/03/2023] [Accepted: 10/21/2023] [Indexed: 10/30/2023]
Abstract
Oral administration is the preferred route of administration based on the convenience for and compliance of the patient. Oral nanomedicines have been developed to overcome the limitations of free drugs and overcome gastrointestinal (GI) barriers, which are heterogeneous across healthy and diseased populations. This review aims to provide a comprehensive overview and comparison of the oral nanomedicine biointeractions in the gastrointestinal tract (GIT) in health and disease (GI and extra-GI diseases) and highlight emerging strategies that exploit these differences for oral nanomedicine-based treatment. We introduce the key GI barriers related to oral delivery and summarize their pathological changes in various diseases. We discuss nanomedicine biointeractions in the GIT in health by describing the general biointeractions based on the type of oral nanomedicine and advanced biointeractions facilitated by advanced strategies applied in this field. We then discuss nanomedicine biointeractions in different diseases and explore how pathological characteristics have been harnessed to advance the development of oral nanomedicine.
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Affiliation(s)
- Cheng Chen
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium
| | - Ana Beloqui
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium; WEL Research Institute, avenue Pasteur, 6, 1300 Wavre, Belgium.
| | - Yining Xu
- Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, West China Hospital, Sichuan University, Chengdu 610041, China; Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
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20
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Wang Y, Ma W, Mehta R, Nguyen LH, Song M, Drew DA, Asnicar F, Huttenhower C, Segata N, Wolf J, Spector T, Berry S, Staller K, Chan AT. Diet and gut microbial associations in irritable bowel syndrome according to disease subtype. Gut Microbes 2023; 15:2262130. [PMID: 37786251 PMCID: PMC10549191 DOI: 10.1080/19490976.2023.2262130] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 09/15/2023] [Indexed: 10/04/2023] Open
Abstract
The role of diet and the gut microbiome in the etiopathogenesis of irritable bowel syndrome (IBS) is not fully understood. Therefore, we investigated the interplay between dietary risk factors and gut microbiota in IBS subtypes using a food frequency questionnaire and stool metagenome data from 969 participants aged 18-65 years in the ZOE PREDICT 1 study, an intervention study designed to predict postprandial metabolic responses. We identified individuals with IBS subtype according to the Rome III criteria based on predominant bowel habits during symptom onset: diarrhea (i.e. looser), constipation (i.e. harder), and mixed. Participants with IBS-D (n = 59) consumed more healthy plant-based foods (e.g. whole grains, leafy vegetables) and fiber, while those with IBS-C (n = 49) tended to consume more unhealthy plant-based foods (e.g. refined grains, fruit juice) than participants without IBS (n = 797). Microbial diversity was nominally lower in patients with IBS-D than in participants without IBS or with IBS-C. Using multivariable-adjusted linear regression, we identified specific microbiota variations in IBS subtypes, including slight increases in pro-inflammatory taxa in IBS-C (e.g. Escherichia coli) and loss of strict anaerobes in IBS-D (e.g. Faecalibacterium prausnitzii). Our analysis also revealed intriguing evidence of interactions between diet and Faecalibacterium prausnitzii. The positive associations between fiber and iron intake and IBS-diarrhea were stronger among individuals with a higher relative abundance of Faecalibacterium prausnitzii, potentially driven by carbohydrate metabolic pathways, including the superpathway of β-D-glucuronide and D-glucuronate degradation. In conclusion, our findings suggest subtype-specific variations in dietary habits, gut microbial composition and function, and diet-microbiota interactions in IBS, providing insights into potential microbiome-informed dietary interventions.
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Affiliation(s)
- Yiqing Wang
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Wenjie Ma
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Raaj Mehta
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Long H. Nguyen
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Mingyang Song
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, USA
| | - David A. Drew
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Francesco Asnicar
- Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy
| | - Curtis Huttenhower
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Nicola Segata
- Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy
- European Institute of Oncology Scientific Institute for Research, Hospitalization and Healthcare, Milan, Italy
| | | | - Tim Spector
- Department of Twin Research, King’s College London, London, UK
| | - Sarah Berry
- Department of Nutritional Sciences, King’s College London, London, UK
| | - Kyle Staller
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Andrew T. Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA
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21
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Marginean CM, Popescu M, Drocas AI, Cazacu SM, Mitrut R, Marginean IC, Iacob GA, Popescu MS, Docea AO, Mitrut P. Gut–Brain Axis, Microbiota and Probiotics—Current Knowledge on Their Role in Irritable Bowel Syndrome: A Review. GASTROINTESTINAL DISORDERS 2023; 5:517-535. [DOI: 10.3390/gidisord5040043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2025] Open
Abstract
Irritable bowel syndrome (IBS) is a common digestive disorder with a significant impact on both individuals and society in terms of quality of life and healthcare costs. A growing body of research has identified various communication pathways between the microbiota and the brain in relation to motility disorders, with the gut–brain axis being key to the pathogenesis of IBS. Multiple factors contribute to the pathogenetic pathways in IBS, including immune mechanisms, psychosocial factors, increased oxidative stress and pro-inflammatory cytokine release, as well as genetic and hormonal factors. Increased permeability of the normal intestinal barrier allows bacterial products to access the lamina propria, providing a mechanism for perpetuating chronic inflammation and characteristic symptoms. The microbiota influences inflammatory processes in IBS by altering the balance between pro-inflammatory factors and host defence. Probiotics modulate the pathophysiological mechanisms involved in IBS by influencing the composition of the microbiota and improving intestinal motility disorders, visceral hypersensitivity, immune function of the intestinal epithelium, metabolic processes in the intestinal lumen, dysfunction of the microbiota-GBA, and are recognised as effective and safe in IBS therapy. Our study aimed to provide a comprehensive overview of the relationship between the gut–brain axis, microbiota, and IBS, based on current information.
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Affiliation(s)
- Cristina Maria Marginean
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Mihaela Popescu
- Department of Endocrinology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Andrei Ioan Drocas
- Department of Urology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Sergiu Marian Cazacu
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Radu Mitrut
- Department of Cardiology, University and Emergency Hospital, 050098 Bucharest, Romania
| | | | - George Alexandru Iacob
- Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Marian Sorin Popescu
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Paul Mitrut
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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22
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Alam MJ, Chen JDZ. Non-invasive neuromodulation: an emerging intervention for visceral pain in gastrointestinal disorders. Bioelectron Med 2023; 9:27. [PMID: 37990288 PMCID: PMC10664460 DOI: 10.1186/s42234-023-00130-5] [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: 08/21/2023] [Accepted: 10/24/2023] [Indexed: 11/23/2023] Open
Abstract
Gastrointestinal (GI) disorders, which extend from the esophagus to the anus, are the most common diseases of the GI tract. Among these disorders, pain, encompassing both abdominal and visceral pain, is a predominant feature, affecting the patients' quality of life and imposing a substantial financial burden on society. Pain signals originating from the gut intricately shape brain dynamics. In response, the brain sends appropriate descending signals to respond to pain through neuronal inhibition. However, due to the heterogeneous nature of the disease and its limited pathophysiological understanding, treatment options are minimal and often controversial. Consequently, many patients with GI disorders use complementary and alternative therapies such as neuromodulation to treat visceral pain. Neuromodulation intervenes in the central, peripheral, or autonomic nervous system by alternating or modulating nerve activity using electrical, electromagnetic, chemical, or optogenetic methodologies. Here, we review a few emerging noninvasive neuromodulation approaches with promising potential for alleviating pain associated with functional dyspepsia, gastroparesis, irritable bowel syndrome, inflammatory bowel disease, and non-cardiac chest pain. Moreover, we address critical aspects, including the efficacy, safety, and feasibility of these noninvasive neuromodulation methods, elucidate their mechanisms of action, and outline future research directions. In conclusion, the emerging field of noninvasive neuromodulation appears as a viable alternative therapeutic avenue for effectively managing visceral pain in GI disorders.
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Affiliation(s)
- Md Jahangir Alam
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
| | - Jiande D Z Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
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23
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Gao Y, Ding P, Wang J, Zhang C, Ji G, Wu T. Application of metabolomics in irritable bowel syndrome in recent 5 years. Int Immunopharmacol 2023; 124:110776. [PMID: 37603947 DOI: 10.1016/j.intimp.2023.110776] [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: 01/04/2023] [Revised: 08/02/2023] [Accepted: 08/06/2023] [Indexed: 08/23/2023]
Abstract
Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders worldwide, characterized by chronic abdominal pain or discomfort and altered bowel habits. To date, the exact pathogenesis of IBS remains elusive, but is clearly multifactorial, including environmental and host factors. However, the management of patients with IBS is challenging and the current diagnostic and therapeutic modalities have unsatisfactory outcomes. Therefore, it is important to develop more effective methods to diagnose IBS early. Metabolomics studies the metabolites most closely related to patient characteristics, which can provide useful clinical biomarkers that can be applied to IBS and may open up new diagnostic approaches. Traditional Chinese medicine (TCM) can play a role in improving symptoms and protecting target organs, but its mechanism needs to be studied in depth. In this review, based on PubMed/MEDLINE and other databases, we searched metabolomics studies related to IBS in the past 5 years, including those related to clinical studies and animal studies, as well as literatures on TCM interventions in IBS, to provide an updated overview of the application of metabolomics to the diagnosis and treatment of IBS and the improvement of IBS by TCM.
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Affiliation(s)
- Ying Gao
- Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Peilun Ding
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Junmin Wang
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Caiyun Zhang
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Guang Ji
- Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
| | - Tao Wu
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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24
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De Barra C, O'Shea D, Hogan AE. NK cells vs. obesity: A tale of dysfunction & redemption. Clin Immunol 2023; 255:109744. [PMID: 37604354 DOI: 10.1016/j.clim.2023.109744] [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: 06/01/2023] [Revised: 08/08/2023] [Accepted: 08/15/2023] [Indexed: 08/23/2023]
Abstract
Natural killer (NK) cells are critical in protecting the body against infection and cancer. NK cells can rapidly respond to these threats by directly targeting the infected or transformed cell using their cytotoxic machinery or by initiating and amplifying the immune response via their production of cytokines. Additionally, NK cells are resident across many tissues including adipose, were their role extends from host protection to tissue homeostasis. Adipose resident NK cells can control macrophage polarization via cytokine production, whilst also regulating stressed adipocyte fate using their cytotoxic machinery. Obesity is strongly associated with increased rates of cancer and a heightened susceptibility to severe infections. This is in part due to significant obesity-related immune dysregulation, including defects in both peripheral and adipose tissue NK cells. In this review, we detail the literature to date on NK cells in the setting of obesity - outlining the consequences, mechanisms and therapeutic interventions.
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Affiliation(s)
- Conor De Barra
- Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co Kildare, Ireland
| | - Donal O'Shea
- Obesity Immunology Group, Education and Research Centre, St Vincent's University Hospital, University College, Dublin 4, Ireland
| | - Andrew E Hogan
- Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co Kildare, Ireland; National Children's Research Centre, Dublin 12, Ireland.
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25
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Qu Y, Park SH, Dallas DC. Evaluating the Potential of Casein Glycomacropeptide in Adult Irritable Bowel Syndrome Management: A Pilot Study. Nutrients 2023; 15:4174. [PMID: 37836457 PMCID: PMC10574033 DOI: 10.3390/nu15194174] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/22/2023] [Accepted: 09/26/2023] [Indexed: 10/15/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that affects 10-15% of the global population and presents symptoms such as abdominal discomfort, bloating and altered bowel habits. IBS is believed to be influenced by gut microbiota alterations and low-grade inflammation. Bovine kappa-casein glycomacropeptide (GMP), a bioactive dairy-derived peptide, possesses anti-adhesive, prebiotic and immunomodulatory properties that could potentially benefit IBS patients. This pilot study investigated the effects of daily supplementation with 30 g of GMP for three weeks on gut health in five people with IBS. We assessed alterations in gut microbiota composition, fecal and blood inflammatory makers, and gut-related symptoms before, during and after the GMP feeding period. The results revealed no changes in fecal microbiota, subtle effects on systemic and intestinal immune makers, and no changes in gut-related symptoms during and after the GMP supplementation. Further research is needed to assess the potential benefits of GMP in IBS patients, including the examination of dosage and form of GMP supplementation.
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Affiliation(s)
- Yunyao Qu
- Department of Food Science & Technology, Oregon State University, Corvallis, OR 97331, USA;
- Nutrition Program, College of Health, Oregon State University, Corvallis, OR 97331, USA
| | - Si Hong Park
- Department of Food Science & Technology, Oregon State University, Corvallis, OR 97331, USA;
| | - David C. Dallas
- Nutrition Program, College of Health, Oregon State University, Corvallis, OR 97331, USA
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26
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Qu Y, Park SH, Dallas DC. The Role of Bovine Kappa-Casein Glycomacropeptide in Modulating the Microbiome and Inflammatory Responses of Irritable Bowel Syndrome. Nutrients 2023; 15:3991. [PMID: 37764775 PMCID: PMC10538225 DOI: 10.3390/nu15183991] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 09/10/2023] [Accepted: 09/12/2023] [Indexed: 09/29/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder marked by chronic abdominal pain, bloating, and irregular bowel habits. Effective treatments are still actively sought. Kappa-casein glycomacropeptide (GMP), a milk-derived peptide, holds promise because it can modulate the gut microbiome, immune responses, gut motility, and barrier functions, as well as binding toxins. These properties align with the recognized pathophysiological aspects of IBS, including gut microbiota imbalances, immune system dysregulation, and altered gut barrier functions. This review delves into GMP's role in regulating the gut microbiome, accentuating its influence on bacterial populations and its potential to promote beneficial bacteria while inhibiting pathogenic varieties. It further investigates the gut microbial shifts observed in IBS patients and contemplates GMP's potential for restoring microbial equilibrium and overall gut health. The anti-inflammatory attributes of GMP, especially its impact on vital inflammatory markers and capacity to temper the low-grade inflammation present in IBS are also discussed. In addition, this review delves into current research on GMP's effects on gut motility and barrier integrity and examines the changes in gut motility and barrier function observed in IBS sufferers. The overarching goal is to assess the potential clinical utility of GMP in IBS management.
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Affiliation(s)
- Yunyao Qu
- Department of Food Science & Technology, Oregon State University, Corvallis, OR 97331, USA; (Y.Q.); (S.H.P.)
- Nutrition Program, College of Health, Oregon State University, Corvallis, OR 97331, USA
| | - Si Hong Park
- Department of Food Science & Technology, Oregon State University, Corvallis, OR 97331, USA; (Y.Q.); (S.H.P.)
| | - David C. Dallas
- Department of Food Science & Technology, Oregon State University, Corvallis, OR 97331, USA; (Y.Q.); (S.H.P.)
- Nutrition Program, College of Health, Oregon State University, Corvallis, OR 97331, USA
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27
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Salmeri N, Sinagra E, Dolci C, Buzzaccarini G, Sozzi G, Sutera M, Candiani M, Ungaro F, Massimino L, Danese S, Mandarino FV. Microbiota in Irritable Bowel Syndrome and Endometriosis: Birds of a Feather Flock Together-A Review. Microorganisms 2023; 11:2089. [PMID: 37630649 PMCID: PMC10458414 DOI: 10.3390/microorganisms11082089] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 08/09/2023] [Accepted: 08/09/2023] [Indexed: 08/27/2023] Open
Abstract
Endometriosis and irritable bowel syndrome (IBS) are chronic conditions affecting up to 10% of the global population, imposing significant burdens on healthcare systems and patient quality of life. Interestingly, around 20% of endometriosis patients also present with symptoms indicative of IBS. The pathogenesis of both these multifactorial conditions remains to be fully elucidated, but connections to gut microbiota are becoming more apparent. Emerging research underscores significant differences in the gut microbiota composition between healthy individuals and those suffering from either endometriosis or IBS. Intestinal dysbiosis appears pivotal in both conditions, exerting an influence via similar mechanisms. It impacts intestinal permeability, triggers inflammatory reactions, and initiates immune responses. Furthermore, it is entwined in a bidirectional relationship with the brain, as part of the gut-brain axis, whereby dysbiosis influences and is influenced by mental health and pain perception. Recent years have witnessed the development of microbiota-focused therapies, such as low FODMAP diets, prebiotics, probiotics, antibiotics, and fecal microbiota transplantation, designed to tackle dysbiosis and relieve symptoms. While promising, these treatments present inconsistent data, highlighting the need for further research. This review explores the evidence of gut dysbiosis in IBS and endometriosis, underscoring the similar role of microbiota in both conditions. A deeper understanding of this common mechanism may enable enhanced diagnostics and therapeutic advancements.
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Affiliation(s)
- Noemi Salmeri
- Gynecology/Obstetrics Unit, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (C.D.); (G.B.); (M.C.)
| | - Emanuele Sinagra
- Gastroenterology & Endoscopy Unit, Fondazione Istituto G. Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy;
| | - Carolina Dolci
- Gynecology/Obstetrics Unit, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (C.D.); (G.B.); (M.C.)
| | - Giovanni Buzzaccarini
- Gynecology/Obstetrics Unit, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (C.D.); (G.B.); (M.C.)
| | - Giulio Sozzi
- Gynecology/Obstetrics Unit, Fondazione Istituto G. Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy; (G.S.); (M.S.)
| | - Miriam Sutera
- Gynecology/Obstetrics Unit, Fondazione Istituto G. Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy; (G.S.); (M.S.)
| | - Massimo Candiani
- Gynecology/Obstetrics Unit, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (C.D.); (G.B.); (M.C.)
| | - Federica Ungaro
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (F.U.); (L.M.); (S.D.); (F.V.M.)
| | - Luca Massimino
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (F.U.); (L.M.); (S.D.); (F.V.M.)
| | - Silvio Danese
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (F.U.); (L.M.); (S.D.); (F.V.M.)
| | - Francesco Vito Mandarino
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (F.U.); (L.M.); (S.D.); (F.V.M.)
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28
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Lutgendorf SK, Zia S, Luo Y, O'Donnell M, van Bokhoven A, Bradley CS, Gallup R, Pierce J, Taple BJ, Naliboff BD, Quentin Clemens J, Kreder KJ, Schrepf A. Early and recent exposure to adversity, TLR-4 stimulated inflammation, and diurnal cortisol in women with interstitial cystitis/bladder pain syndrome: A MAPP research network study. Brain Behav Immun 2023; 111:116-123. [PMID: 37001828 PMCID: PMC10474614 DOI: 10.1016/j.bbi.2023.03.024] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 03/01/2023] [Accepted: 03/27/2023] [Indexed: 04/13/2023] Open
Abstract
Both early (ELA) and recent life adversity (RLA) have been linked with chronic pain conditions and persistent alterations of neuroendocrine and inflammatory responses. Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic urologic disorder characterized by bladder and/or pelvic pain, and excessive urinary frequency and/or urgency. IC/BPS has been associated with high levels of ELA as well as a distinct inflammatory signature. However, associations between ELA and RLA with inflammatory mechanisms in IC/BPS that might underlie the link between adversity and symptoms have not been examined. Here we investigated ELA and RLA in women with IC/BPS as potential risk factors for inflammatory processes and hypothalamic-pituitaryadrenal (HPA) abnormalities using data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. Women with IC/BPS and healthy controls (n = 154 and 32, respectively) completed surveys, collected salivary cortisol at awakening and bedtime for 3 days, and gave a blood sample which was analyzed for 7 LPS-stimulated cytokines and chemokines (IL-6, TNFα, IL-1β, MIP1α, MCP1, IL-8, and IL-10). Two cytokine/chemokine composites were identified using principal components analysis. Patients with greater exposure to RLA or cumulative ELA and RLA of at least moderate severity showed elevated levels of a composite of all cytokines, adjusting for age, body mass index, and study site. Furthermore, there was a trending relationship between ELA and the pro-inflammatory composite score. Nocturnal cortisol and cortisol slope were not associated with ELA, RLA, or inflammation. The present findings support the importance of adverse events in IC/BPS via a biological mechanism and suggest that ELA and RLA should be assessed as risk factors for inflammation as part of a clinical workup for IC/BPS.
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Affiliation(s)
- Susan K Lutgendorf
- Department of Psychological & Brain Sciences, University of Iowa, Iowa City, IA, USA; Department of Urology, University of Iowa, Iowa City, IA, USA; Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USA.
| | - Sharaf Zia
- Department of Psychological & Brain Sciences, University of Iowa, Iowa City, IA, USA
| | - Yi Luo
- Department of Urology, University of Iowa, Iowa City, IA, USA
| | | | - Adrie van Bokhoven
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Catherine S Bradley
- Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USA
| | - Robert Gallup
- Department of Mathematics, West Chester University, West Chester, PA, USA
| | - Jennifer Pierce
- Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA
| | - Bayley J Taple
- Department of Preventative Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Bruce D Naliboff
- Department of Medicine David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA
| | | | - Karl J Kreder
- Department of Urology, University of Iowa, Iowa City, IA, USA
| | - Andrew Schrepf
- Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA
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Bora G, Atkinson SN, Pan A, Sood M, Salzman N, Karrento K. Impact of auricular percutaneous electrical nerve field stimulation on gut microbiome in adolescents with irritable bowel syndrome: A pilot study. J Dig Dis 2023; 24:348-358. [PMID: 37448237 DOI: 10.1111/1751-2980.13203] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 05/07/2023] [Accepted: 07/11/2023] [Indexed: 07/15/2023]
Abstract
OBJECTIVES Percutaneous electrical nerve field stimulation (PENFS) has documented efficacy for irritable bowel syndrome (IBS) via plausible vagal neuromodulation effects. The vagus nerve may affect gut microbiome composition via brain-gut-microbiome signaling. We aimed to investigate gut microbiome alterations by PENFS therapy in adolescent IBS patients. METHODS A prospective study of females with IBS aged 11-18 years receiving PENFS therapy for 4 weeks with pre- and post-intervention stool sampling was conducted. Outcome surveys completed pre-therapy, weekly, and post-therapy included IBS-Severity Scoring System (IBS-SSS), Visceral Sensitivity Index (VSI), Functional Disability Inventory (FDI), and the global symptom response scale (SRS). Bacterial DNA was extracted from stool samples followed by 16S rRNA amplification and sequencing. QIIME 2 (version 2022.2) was used for analyses of α and β diversity and differential abundance by group. RESULTS Twenty females aged 15.6 ± 1.62 years were included. IBS-SSS, VSI, and FDI scores decreased significantly after PENFS therapy (P < 0.0001, P = 0.0003, P = 0.0004, respectively). No intra- or interindividual microbiome changes were noted pre- versus post-therapy or between responders and non-responders. When response was defined by 50-point IBS-SSS score reduction, α diversity was higher in responders compared with non-responders at week 4 (P = 0.033). There was higher abundance of Blautia in excellent responders versus non-responders. CONCLUSIONS There were no substantial microbial diversity alterations with PENFS. Subjects with excellent therapeutic response showed an enrichment of relative abundance of Blautia, which may indicate that patients with specific microbial signature have a more favorable response to PENFS.
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Affiliation(s)
- Geetanjali Bora
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Samantha N Atkinson
- Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
- Center for Microbiome Research, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Amy Pan
- Center for Microbiome Research, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
- Divison of Quantitative Health Sciences, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Manu Sood
- Division of Pediatric Gastroenterology, Department of Pediatrics, University of Illinois College of Medicine Peoria, Peoria, Illinois, USA
| | - Nita Salzman
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
- Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
- Center for Microbiome Research, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Katja Karrento
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
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30
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Konstantis G, Efstathiou S, Pourzitaki C, Kitsikidou E, Germanidis G, Chourdakis M. Efficacy and safety of probiotics in the treatment of irritable bowel syndrome: A systematic review and meta-analysis of randomised clinical trials using ROME IV criteria. Clin Nutr 2023; 42:800-809. [PMID: 37031468 DOI: 10.1016/j.clnu.2023.03.019] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 03/18/2023] [Accepted: 03/25/2023] [Indexed: 04/03/2023]
Abstract
BACKGROUND Irritable Bowel Syndrome (IBS) is a functional gastrointestinal disorder which affects a great number of patients globally. Clinical trials and meta-analyses have evaluated different therapies for IBS. Some of them have shown that probiotics play a significant role in the management of IBS-patients. Nevertheless, results are controversial, and the efficacy of the administration of probiotics remains to be confirmed, especially in regard to which type of probiotic-strains are beneficial. AIM The aim of the present meta-analysis is to assess the efficacy and safety of the administration of probiotics to IBS-patients with a diagnosis based on Rome IV criteria, which is performed for the first time. METHODS Electronic databases (Pubmed, Scopus and Cochrane) were searched until 26.01.2023 for randomized controlled trials (RCTs) studying the administration of probiotics in adult IBS-patients, who were categorized according to the Rome IV criteria. The risk of bias was assessed using the Cochrane Risk of Bias tool (ROB) 2.0. Weighted and standardized mean difference with the 95% confidence intervals were used for the synthesis of the results. Primary outcomes were the decrease of IBS-Symptom Severity Score (IBS-SSS) and decrease of abdominal pain. The secondary outcomes were the improvement in quality of life (QoL) and the decrease of bloating. Lastly, the adverse effects of probiotics were evaluated. The protocol of the study has been registered at protocols.io (DOI dx.doi.org/10.17504/protocols.io.14egn218yg5d/v1). RESULTS Six double-blind (N = 970) placebo-control RCTs fulfilled the inclusion criteria and overall, nine different strains of probiotics were examined. No significant reduction in IBS-SSS (WMD -43.2, 95% CI -87.5 to 1.0, I2 = 82.9%) was demonstrated, whereas a significant decrease regarding abdominal pain (SMD -0.94, 95% CI -1.53 to -0.35, I2 = 92,2) was shown. Furthermore, no correlation between improvement of QoL and the use of probiotics (SMD -0.64, 95% CI -1.27 to 0.00, I2 = 93,9%) was shown. However, probiotics were associated with a significant reduction in bloating (SMD -0.28, 95% CI -0.47 to -0.09, I2 = 36,0%). A qualitative synthesis was conducted about adverse events and showed that the use of probiotics' is safe without severe adverse events. CONCLUSIONS The administration of probiotics to IBS-patients demonstrated a positive effect on pain and bloating, but due to significant heterogeneity and confounding factors, that were not examined in the included studies, a definitive statement cannot be made. Moreover, probiotics did not lead to an improvement in other parameters. There is a need for larger RCTs in IBS-patients diagnosed according to Rome IV (not III) criteria and especially it is essential to be conducted RCTs which examine the administration of specific strains and have similar methodological characteristics.
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Affiliation(s)
- Georgios Konstantis
- Clinical Pharmacology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Essen, Germany
| | - Stylianos Efstathiou
- Clinical Pharmacology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Chryssa Pourzitaki
- Clinical Pharmacology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| | - Elisavet Kitsikidou
- Department of Internal Medicine, Evangelical Hospital Dusseldorf, Dusseldorf, Germany
| | - Georgios Germanidis
- Division of Gastroenterology and Hepatology, 1st Department of Internal Medicine, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Michail Chourdakis
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Pretorius L, Smith C. Tyramine-induced gastrointestinal dysregulation is attenuated via estradiol associated mechanisms in a zebrafish larval model. Toxicol Appl Pharmacol 2023; 461:116399. [PMID: 36716863 DOI: 10.1016/j.taap.2023.116399] [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: 09/28/2022] [Revised: 01/06/2023] [Accepted: 01/19/2023] [Indexed: 01/30/2023]
Abstract
Development of targeted therapeutics to alleviate gastrointestinal (GI) inflammation and its debilitating consequences are required. In this context, the trace aminergic system may link together sex, diet and inflammation. Utilising a zebrafish larval model of GI inflammation, the current study aimed to investigate mechanisms by which excess amounts of trace amines (TAs) may influence GI health. In addition, we probed the potential role of 17β-estradiol (E2) and its receptors, given the known female-predominance of many GI disorders. To assess GI functionality and integrity, live imaging techniques (neutral red staining) and post-mortem immunofluorescent staining of tight junction proteins (occludin and ZO-1) were analyzed respectively. In addition, behavioural assays, as an indication of overall wellbeing, as well as whole body H2O2 and prostaglandin E2 assays were performed to inform on oxidative and inflammatory status. Excess β-phenethylamine (PEA), tryptamine (TRP) and ρ-tyramine (TYR) resulted in adverse GI and systemic effects. In this regard, clear beneficial effects of E2 to modulate the effects of PEA, TRP and TYR was evident. Moreover, agmatine displayed potential protective effects on GI epithelium and whole body oxidative status, however, potential to induce systemic inflammation suggests the importance of dosage and administration optimisation. Taken together, TYR seems like the most prominent TA to have damaging GI effects, feasibly exacerbating GI inflammation. In this context, the relative lack of E2 may provide mechanistic insights into the reported female-predominance of GI disorders. Moreover, an effective therapeutic in this context may be required to maintain GI TA load despite fluctuating E2 levels.
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Affiliation(s)
- L Pretorius
- Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa
| | - C Smith
- Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa.
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32
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Chi ZC. Progress in research of low-grade inflammation in irritable bowel syndrome. Shijie Huaren Xiaohua Zazhi 2022; 30:1051-1065. [DOI: 10.11569/wcjd.v30.i24.1051] [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] [Indexed: 12/27/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a common intestinal disease with a prevalence of 10%-15%. However, its pathophysiology is still not completely clear, and it has long been considered as a functional disease. In recent years, it has been found that low-grade inflammation plays a pathogenic role in IBS. Studies have confirmed that there is persistent mucosal inflammation at the microscopic and molecular levels. This review discusses the evidence, role, and clinical relevance of mucosal inflammation in IBS. In addition to mucosal inflammation, neuroinflammation may lead to changes in neuroendocrine pathways and glucocorticoid receptor genes through the "gut-brain" axis, and thus cause IBS through proinflammatory phenotype and hypothalamic pituitary adrenal axis and 5-hydroxytryptamine dysfunction. The observation that IBS patients can benefit from anti-inflammatory therapy also confirms that IBS is associated with inflammation.
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Affiliation(s)
- Zhao-Chun Chi
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China
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Saneie S, Aminianfar A, Shidfar F, Keshteli AH, Esmaillzadeh A, Adibi P. The association between dietary total antioxidant capacity and odds and severity of irritable bowel syndrome among Iranian adults: a cross-sectional study. BMC Gastroenterol 2022; 22:472. [PMID: 36402962 PMCID: PMC9675204 DOI: 10.1186/s12876-022-02531-3] [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: 05/12/2022] [Accepted: 10/04/2022] [Indexed: 11/21/2022] Open
Abstract
Background Little evidence is available in terms of the role of dietary antioxidants in the management of irritable bowel syndrome (IBS) disease. This study aimed to examine the association between dietary total antioxidant capacity (dTAC) and odds of IBS and its severity. Methods This cross-sectional study was conducted on 3,362 Iranian adults who were referred to health centers in Isfahan province, Iran. Participants' dietary intakes were collected using a semi-quantitative validated food frequency questionnaire (DS-FFQ). The dTAC was measured by the ferric-reducing antioxidant power (FRAP) method. Multivariable binary or ordinal logistic regression analyses were performed to estimate any associations between dTAC and odds of IBS, IBS severity, and IBS subtypes. Results The average age and BMI of the participants and dTAC score were 36.3 ± 7.87 year, 24.9 ± 3.82 kg/m2. The prevalence of IBS, IBS with constipation (IBS-C), IBS with diarrhoea (IBS-D), mixed IBS (IBS-M), and un-subtyped IBS (IBS-U) were 22.2, 7.5, 4.6, 3.8, and 6.2%, respectively. In crude and adjusted models, the results did not show any significant association between dTAC and odds of IBS among whole and gender-age stratified populations. Being in the third compared with the first tertile of dTAC was not also significantly associated with odds of IBS severity. Besides, there were no significant associations between dTAC and odds of IBS-C, IBS-D, IBS-M, and IBS-U. Conclusion This study indicates that dTAC may not be associated with the odds of IBS and its severity even after stratification for gender and body mass index.
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Affiliation(s)
- Solaleh Saneie
- grid.411746.10000 0004 4911 7066Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Azadeh Aminianfar
- grid.444768.d0000 0004 0612 1049Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Farzad Shidfar
- grid.411746.10000 0004 4911 7066Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | | | - Ahmad Esmaillzadeh
- grid.411705.60000 0001 0166 0922Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, P.O. Box 14155-6117, Tehran, Iran ,grid.411705.60000 0001 0166 0922Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran ,grid.411036.10000 0001 1498 685XDepartment of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Peyman Adibi
- grid.411036.10000 0001 1498 685XIntegrative Functional Gastroenterology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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Wu S, Yuan C, Yang Z, Liu S, Zhang Q, Zhang S, Zhu S. Non-alcoholic fatty liver is associated with increased risk of irritable bowel syndrome: a prospective cohort study. BMC Med 2022; 20:262. [PMID: 35989356 PMCID: PMC9394037 DOI: 10.1186/s12916-022-02460-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 07/04/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The relationship between non-alcoholic fatty liver degree as well as non-alcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS) remains poorly understood. We aimed to investigate the prospective association of non-alcoholic fatty liver degree as well as NAFLD with incident IBS in a large-scale population-based cohort. METHODS Participants free of IBS, coeliac disease, inflammatory bowel disease, alcoholic liver disease, and any cancer at baseline from the UK Biobank were included. Non-alcoholic fatty liver degree was measured by a well-validated fatty liver index (FLI), with FLI ≥ 60 as an indicator of NAFLD. Primary outcome was incident IBS. Cox proportional hazard model was used to investigate the associated risk of incident IBS. RESULTS Among 396,838 participants (mean FLI was 48.29 ± 30.07), 153,203(38.6%) were with NAFLD diagnosis at baseline. During a median of 12.4-year follow-up, 7129 cases of incident IBS were identified. Compared with non-NAFLD, NAFLD patients showed a 13% higher risk of developing IBS (HR = 1.13, 95%CI: 1.05-1.17) after multivariable adjustment. Compared with the lowest, the highest FLI quartile was associated with a significantly increased risk of IBS (HRQ4 VS Q1 = 1.21, 1.13-1.30, Ptrend < 0.001). Specifically, the positive association between non-alcoholic fatty liver degree and IBS was also observed by per SD change of FLI (adjusted HR = 1.08, 1.05-1.10). Further sensitivity analysis and subgroup analysis indicated similar results, with the positive association particularly observed in females, but not in males. CONCLUSIONS High degree of non-alcoholic fatty liver as well as non-alcoholic fatty liver disease is associated with increased risk of incident IBS. Further studies are warranted to confirm the findings and elucidate the underlying biological mechanisms.
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Affiliation(s)
- Shanshan Wu
- Department of Gastroenterology, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Changzheng Yuan
- School of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA
| | - Zhirong Yang
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.,Primary Care Unit, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, CB18RN, UK
| | - Si Liu
- Department of Gastroenterology, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Qian Zhang
- Department of Gastroenterology, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Shutian Zhang
- Department of Gastroenterology, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Shengtao Zhu
- Department of Gastroenterology, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
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Pawlik RJ, Petrakova L, Brotte L, Engler H, Benson S, Elsenbruch S. Circulating Pro-inflammatory Cytokines Do Not Explain Interindividual Variability in Visceral Sensitivity in Healthy Individuals. Front Neurosci 2022; 16:876490. [PMID: 35860299 PMCID: PMC9289472 DOI: 10.3389/fnins.2022.876490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 06/10/2022] [Indexed: 11/13/2022] Open
Abstract
A role of the immune system in the pathophysiology of pain and hyperalgesia has received growing attention, especially in the context of visceral pain and the gut-brain axis. While acute experimental inflammation can induce visceral hyperalgesia as part of sickness behavior in healthy individuals, it remains unclear if normal plasma levels of circulating pro-inflammatory cytokines contribute to interindividual variability in visceral sensitivity. We herein compiled data from a tightly screened and well-characterized sample of healthy volunteers (N = 98) allowing us to assess associations between visceral sensitivity and gastrointestinal symptoms, and plasma concentrations of three selected pro-inflammatory cytokines (i.e., TNF-α, IL-6, and IL-8), along with cortisol and stress-related psychological variables. For analyses, we compared subgroups created to have distinct pro-inflammatory cytokine profiles, modelling healthy individuals at putative risk or resilience, respectively, for symptoms of the gut-brain axis, and compared them with respect to rectal sensory and pain thresholds and subclinical GI symptoms. Secondly, we computed multiple regression analyses to test if circulating pro-inflammatory markers predict visceral sensitivity in the whole sample. Despite pronounced subgroup differences in pro-inflammatory cytokine and cortisol concentrations, we observed no differences in measures of visceroception. In regression analyses, cytokines did not emerge as predictors. The pain threshold was predicted by emotional state and trait variables, especially state anxiety, together explaining 10.9% of the variance. These negative results do not support the hypothesis that systemic cytokine levels contribute to normal interindividual variability in visceroception in healthy individuals. Trajectories to visceral hyperalgesia as key marker in disorders of gut-brain interactions likely involve complex interactions of biological and psychological factors in keeping with a psychosocial model. Normal variations in systemic cytokines do not appear to constitute a vulnerability factor in otherwise healthy individuals, calling for prospective studies in at risk populations.
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Affiliation(s)
- Robert J. Pawlik
- Department of Medical Psychology and Medical Sociology, Ruhr University Bochum, Bochum, Germany
| | - Liubov Petrakova
- Department of Medical Psychology and Medical Sociology, Ruhr University Bochum, Bochum, Germany
| | - Lisa Brotte
- Institute of Medical Psychology and Behavioral Immunobiology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Department of Neurology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Harald Engler
- Institute of Medical Psychology and Behavioral Immunobiology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Sven Benson
- Institute of Medical Psychology and Behavioral Immunobiology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Institute for Medical Education, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Sigrid Elsenbruch
- Department of Medical Psychology and Medical Sociology, Ruhr University Bochum, Bochum, Germany
- Department of Neurology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- *Correspondence: Sigrid Elsenbruch,
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Lucarini E, Di Pilato V, Parisio C, Micheli L, Toti A, Pacini A, Bartolucci G, Baldi S, Niccolai E, Amedei A, Rossolini GM, Nicoletti C, Cryan JF, O'Mahony SM, Ghelardini C, Di Cesare Mannelli L. Visceral sensitivity modulation by faecal microbiota transplantation: the active role of gut bacteria in pain persistence. Pain 2022; 163:861-877. [PMID: 34393197 PMCID: PMC9009324 DOI: 10.1097/j.pain.0000000000002438] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 07/19/2021] [Accepted: 08/02/2021] [Indexed: 11/25/2022]
Abstract
Recent findings linked gastrointestinal disorders characterized by abdominal pain to gut microbiota composition. The present work aimed to evaluate the power of gut microbiota as a visceral pain modulator and, consequently, the relevance of its manipulation as a therapeutic option in reversing postinflammatory visceral pain persistence. Colitis was induced in mice by intrarectally injecting 2,4-dinitrobenzenesulfonic acid (DNBS). The effect of faecal microbiota transplantation from viscerally hypersensitive DNBS-treated and naive donors was evaluated in control rats after an antibiotic-mediated microbiota depletion. Faecal microbiota transplantation from DNBS donors induced a long-lasting visceral hypersensitivity in control rats. Pain threshold trend correlated with major modifications in the composition of gut microbiota and short chain fatty acids. By contrast, no significant alterations of colon histology, permeability, and monoamines levels were detected. Finally, by manipulating the gut microbiota of DNBS-treated animals, a counteraction of persistent visceral pain was achieved. The present results provide novel insights into the relationship between intestinal microbiota and visceral hypersensitivity, highlighting the therapeutic potential of microbiota-targeted interventions.
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Affiliation(s)
- Elena Lucarini
- Department of Neuroscience, Psychology, Drug Research and Child Health, Neurofarba, Pharmacology and Toxicology Section, University of Florence, Florence, Italy
| | - Vincenzo Di Pilato
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
- Clinical Microbiology and Virology Unit, Florence Careggi University Hospital, Florence, Italy
- Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
| | - Carmen Parisio
- Department of Neuroscience, Psychology, Drug Research and Child Health, Neurofarba, Pharmacology and Toxicology Section, University of Florence, Florence, Italy
| | - Laura Micheli
- Department of Neuroscience, Psychology, Drug Research and Child Health, Neurofarba, Pharmacology and Toxicology Section, University of Florence, Florence, Italy
| | - Alessandra Toti
- Department of Neuroscience, Psychology, Drug Research and Child Health, Neurofarba, Pharmacology and Toxicology Section, University of Florence, Florence, Italy
| | - Alessandra Pacini
- Department of Experimental and Clinical Medicine, Anatomy and Histology Section, University of Florence, Florence, Italy
| | - Gianluca Bartolucci
- Department of Neurosciences, Psychology, Drug Research and Child Health Section of Pharmaceutical and Nutraceutical Sciences University of Florence, Florence, Italy
| | - Simone Baldi
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Elena Niccolai
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Gian Maria Rossolini
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
- Clinical Microbiology and Virology Unit, Florence Careggi University Hospital, Florence, Italy
| | - Claudio Nicoletti
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - John F. Cryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Siobhain M. O'Mahony
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Carla Ghelardini
- Department of Neuroscience, Psychology, Drug Research and Child Health, Neurofarba, Pharmacology and Toxicology Section, University of Florence, Florence, Italy
| | - Lorenzo Di Cesare Mannelli
- Department of Neuroscience, Psychology, Drug Research and Child Health, Neurofarba, Pharmacology and Toxicology Section, University of Florence, Florence, Italy
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Tunc T, Ortaakarsu AB, Hatipoglu SM, Kazancı U, Karabocek S, Karabocek N, Dege N, Karacan N. New Schiff bases with a 2,6-bis(2-aminophenylthio)pyridine moiety acting as glutathione reductase activator and inhibitors: Synthesis and molecular docking studies. J Mol Struct 2022. [DOI: 10.1016/j.molstruc.2021.132299] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Burns GL, Talley NJ, Keely S. Immune responses in the irritable bowel syndromes: time to consider the small intestine. BMC Med 2022; 20:115. [PMID: 35354471 PMCID: PMC8969236 DOI: 10.1186/s12916-022-02301-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 02/15/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is considered a disorder of gut-brain interaction (DGBI), presenting as chronic abdominal pain and altered defaecation. Symptoms are often food related. Much work in the field has focused on identifying physiological, immune and microbial abnormalities in the colon of patients; however, evidence of small intestinal immune activation and microbial imbalance has been reported in small studies. The significance of such findings has been largely underappreciated despite a growing body of work implicating small intestinal homeostatic imbalance in the pathogenesis of DGBIs. MAIN TEXT Small intestinal mechanosensation is a characteristic feature of IBS. Furthermore, altered small intestinal barrier functions have been demonstrated in IBS patients with the diarrhoea-predominant subtype. Small intestinal bacterial overgrowth and increased populations of small intestinal mast cells are frequently associated with IBS, implicating microbial imbalance and low-grade inflammation in the pathogenesis of IBS. Furthermore, reports of localised food hypersensitivity responses in IBS patients implicate the small intestine as the site of immune-microbial-food interactions. CONCLUSIONS Given the association of IBS symptoms with food intake in a large proportion of patients and the emerging evidence of immune activation in these patients, the current literature suggests the pathogenesis of IBS is not limited to the colon but rather may involve dysfunction of the entire intestinal tract. It remains unclear if regional variation in IBS pathology explains the various symptom phenotypes and further work should consider the intestinal tract as a whole to answer this question.
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Affiliation(s)
- Grace L Burns
- NHMRC Centre of Research Excellence in Digestive Health, The University of Newcastle, Callaghan, New South Wales, Australia.,College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, New South Wales, Australia.,Immune Health Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
| | - Nicholas J Talley
- NHMRC Centre of Research Excellence in Digestive Health, The University of Newcastle, Callaghan, New South Wales, Australia.,College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, New South Wales, Australia.,Immune Health Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
| | - Simon Keely
- NHMRC Centre of Research Excellence in Digestive Health, The University of Newcastle, Callaghan, New South Wales, Australia. .,College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, New South Wales, Australia. .,Immune Health Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia.
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Mamieva Z, Poluektova E, Svistushkin V, Sobolev V, Shifrin O, Guarner F, Ivashkin V. Antibiotics, gut microbiota, and irritable bowel syndrome: What are the relations? World J Gastroenterol 2022; 28:1204-1219. [PMID: 35431513 PMCID: PMC8968486 DOI: 10.3748/wjg.v28.i12.1204] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 12/01/2021] [Accepted: 02/23/2022] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder in which recurrent abdominal pain is associated with defecation or a change in bowel habits (constipation, diarrhea, or both), and it is often accompanied by symptoms of abdominal bloating and distension. IBS is an important health care issue because it negatively affects the quality of life of patients and places a considerable financial burden on health care systems. Despite extensive research, the etiology and underlying pathophysiology of IBS remain incompletely understood. Proposed mechanisms involved in its pathogenesis include increased intestinal permeability, changes in the immune system, visceral hypersensitivity, impaired gut motility, and emotional disorders. Recently, accumulating evidence has highlighted the important role of the gut microbiota in the development of IBS. Microbial dysbiosis within the gut is thought to contribute to all aspects of its multifactorial pathogenesis. The last few decades have also seen an increasing interest in the impact of antibiotics on the gut microbiota. Moreover, antibiotics have been suggested to play a role in the development of IBS. Extensive research has established that antibacterial therapy induces remarkable shifts in the bacterial community composition that are quite similar to those observed in IBS. This suggestion is further supported by data from cohort and case-control studies, indicating that antibiotic treatment is associated with an increased risk of IBS. This paper summarizes the main findings on this issue and contributes to a deeper understanding of the link between antibiotic use and the development of IBS.
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Affiliation(s)
- Zarina Mamieva
- Department of Internal Disease Propaedeutics, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119991, Russia
| | - Elena Poluektova
- Department of Internal Disease Propaedeutics, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119991, Russia
| | - Valery Svistushkin
- Department of Ear, Throat and Nose Diseases, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119991, Russia
| | - Vasily Sobolev
- Department of Ear, Throat and Nose Diseases, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119991, Russia
| | - Oleg Shifrin
- Department of Internal Disease Propaedeutics, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119991, Russia
| | - Francisco Guarner
- Digestive System Research Unit, Vall d’Hebron Research Institute, Barcelona 08035, Spain
| | - Vladimir Ivashkin
- Department of Internal Disease Propaedeutics, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119991, Russia
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ROS-responsive thioketal-linked alginate/chitosan carriers for irritable bowel syndrome with diarrhea therapy. Int J Biol Macromol 2022; 209:70-82. [PMID: 35351547 DOI: 10.1016/j.ijbiomac.2022.03.118] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 03/09/2022] [Accepted: 03/17/2022] [Indexed: 02/08/2023]
Abstract
A colon-specific carrier that can protect drugs from the destruction in the gastrointestinal tract is critical for treating irritable bowel syndrome with diarrhea (IBS-D). In this study, chitosan was cross-linked by the thioketal (TK) bond to serve as a ROS-sensitive core of microspheres. Then the chitosan core was coated with an alginate shell. The alginate/chitosan microspheres can protect puerarin against the destruction and elimination in the gastrointestinal tract and release puerarin at the lesion sites in large quantities. The microspheres were characterized using differential scanning calorimetry, Fourier-transform infrared spectroscopy, and scanning electron microscopy. The swelling study showed that microspheres would shrink in an acidic environment. The in vitro release analysis indicated that little puerarin was released at gastric pH but burst release was observed in simulated colonic fluid containing H2O2. Fluorescent tracer revealed that the fluorescence of microspheres lasted up to 30 h in the colon, which was beneficial to prolong the action time between puerarin and colon. The in vivo studies indicated that puerarin-loaded microspheres are more effective in the treatment of IBS-D than free puerarin. Altogether, the ROS-responsive alginate/chitosan microspheres may be a promising strategy for IBS-D.
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The Combination of Intestinal Alkaline Phosphatase Treatment with Moderate Physical Activity Alleviates the Severity of Experimental Colitis in Obese Mice via Modulation of Gut Microbiota, Attenuation of Proinflammatory Cytokines, Oxidative Stress Biomarkers and DNA Oxidative Damage in Colonic Mucosa. Int J Mol Sci 2022; 23:ijms23062964. [PMID: 35328382 PMCID: PMC8955215 DOI: 10.3390/ijms23062964] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 03/03/2022] [Accepted: 03/04/2022] [Indexed: 12/16/2022] Open
Abstract
Inflammatory bowel diseases (IBD) are commonly considered as Crohn's disease and ulcerative colitis, but the possibility that the alterations in gut microbiota and oxidative stress may affect the course of experimental colitis in obese physically exercising mice treated with the intestinal alkaline phosphatase (IAP) has been little elucidated. Mice fed a high-fat-diet (HFD) or normal diet (ND) for 14 weeks were randomly assigned to exercise on spinning wheels (SW) for 7 weeks and treated with IAP followed by intrarectal administration of TNBS. The disease activity index (DAI), grip muscle strength test, oxidative stress biomarkers (MDA, SOD, GSH), DNA damage (8-OHdG), the plasma levels of cytokines IL-2, IL-6, IL-10, IL-12p70, IL-17a, TNF-α, MCP-1 and leptin were assessed, and the stool composition of the intestinal microbiota was determined by next generation sequencing (NGS). The TNBS-induced colitis was worsened in obese sedentary mice as manifested by severe colonic damage, an increase in DAI, oxidative stress biomarkers, DNA damage and decreased muscle strength. The longer running distance and weight loss was observed in mice given IAP or subjected to IAP + SW compared to sedentary ones. Less heterogeneous microbial composition was noticed in sedentary obese colitis mice and this effect disappeared in IAP + SW mice. Absence of Alistipes, lower proportion of Turicibacter, Proteobacteria and Faecalibacterium, an increase in Firmicutes and Clostridium, a decrease in oxidative stress biomarkers, 8-OHdG content and proinflammatory cytokines were observed in IAP + SW mice. IAP supplementation in combination with moderate physical activity attenuates the severity of murine colitis complicated by obesity through a mechanism involving the downregulation of the intestinal cytokine/chemokine network and oxidative stress, the modulation of the gut microbiota and an improvement of muscle strength.
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Ameliorative Effects of Humulus japonicus Extract and Polysaccharide-Rich Extract of Phragmites rhizoma in Rats with Gastrointestinal Dysfunctions Induced by Water Avoidance Stress. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:9993743. [PMID: 35096122 PMCID: PMC8799342 DOI: 10.1155/2022/9993743] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 12/10/2021] [Accepted: 12/15/2021] [Indexed: 12/16/2022]
Abstract
Chronic stress can cause the gastrointestinal disorders characterized by an altered bowel movement and abdominal pain. Studies have shown that Humulus japonicus extract (HJE) has anti-inflammatory and antidiarrheal effects, and Phragmites rhizoma extract (PEP) has antioxidative and antistress effects. The present study aimed to investigate the possible effects of HJE and PEP in rat models with stress-induced gastrointestinal dysfunctions. The rats were exposed to water avoidance stress (WAS, 1 h/day) for 10 days to induce gastrointestinal disorders. We found that WAS significantly increased fecal pellet output during 1 h stress, gastric emptying, colonic contractility, and permeability compared to the normal rats. Pretreatment with HJE and PEP (0.25 and 0.5 mL/kg, both administered separately) improved the increased gastric emptying and colonic contractility induced by electrical field stimulation, acetylcholine, and serotonin and also alleviated the increased colonic permeability. HJE and PEP also increased the claudin-1 and occludin expressions, reduced by WAS. WAS increased the concentration of TNF-α and TBARS and reduced FRAP. HJE and PEP recovered these effects. HJE and PEP improved the gastrointestinal disorders induced by WAS by upregulating the tight junction protein, possibly acting on cholinergic and serotonergic receptors to abolish the colonic hypercontractility and hyperpermeability and degradation of inflammatory cytokines via an antioxidant effect.
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Hillestad EMR, van der Meeren A, Nagaraja BH, Bjørsvik BR, Haleem N, Benitez-Paez A, Sanz Y, Hausken T, Lied GA, Lundervold A, Berentsen B. Gut bless you: The microbiota-gut-brain axis in irritable bowel syndrome. World J Gastroenterol 2022; 28:412-431. [PMID: 35125827 PMCID: PMC8790555 DOI: 10.3748/wjg.v28.i4.412] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 06/24/2021] [Accepted: 01/13/2022] [Indexed: 12/16/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a common clinical label for medically unexplained gastrointestinal symptoms, recently described as a disturbance of the microbiota-gut-brain axis. Despite decades of research, the pathophysiology of this highly heterogeneous disorder remains elusive. However, a dramatic change in the understanding of the underlying pathophysiological mechanisms surfaced when the importance of gut microbiota protruded the scientific picture. Are we getting any closer to understanding IBS' etiology, or are we drowning in unspecific, conflicting data because we possess limited tools to unravel the cluster of secrets our gut microbiota is concealing? In this comprehensive review we are discussing some of the major important features of IBS and their interaction with gut microbiota, clinical microbiota-altering treatment such as the low FODMAP diet and fecal microbiota transplantation, neuroimaging and methods in microbiota analyses, and current and future challenges with big data analysis in IBS.
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Affiliation(s)
- Eline Margrete Randulff Hillestad
- Department of Clinical Medicine, University of Bergen, Bergen 5021, Norway
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
| | - Aina van der Meeren
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
| | - Bharat Halandur Nagaraja
- Mohn Medical Imaging and Visualization Center, Department of Radiology, Haukeland University Hospital, Bergen 5021, Norway
| | - Ben René Bjørsvik
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
- Mohn Medical Imaging and Visualization Center, Department of Radiology, Haukeland University Hospital, Bergen 5021, Norway
| | - Noman Haleem
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
- Mohn Medical Imaging and Visualization Center, Department of Radiology, Haukeland University Hospital, Bergen 5021, Norway
| | - Alfonso Benitez-Paez
- Host-Microbe Interactions in Metabolic Health Laboratory, Principe Felipe Research Center, Valencia 46012, Spain
| | - Yolanda Sanz
- Microbial Ecology, Nutrition and Health Research Unit, Institute of Agrochemistry and Food Technology, National Research Council, Paterna-Valencia 46980, Spain
| | - Trygve Hausken
- Department of Clinical Medicine, University of Bergen, Bergen 5021, Norway
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
| | - Gülen Arslan Lied
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen 5021, Norway
| | - Arvid Lundervold
- Mohn Medical Imaging and Visualization Center, Department of Radiology, Haukeland University Hospital, Bergen 5021, Norway
- Department of Biomedicine, University of Bergen, Bergen 5021, Norway
| | - Birgitte Berentsen
- Department of Clinical Medicine, University of Bergen, Bergen 5021, Norway
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
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Mirzaie Z, Bastani A, Haji-Aghamohammadi AA, Rashidi Nooshabadi M, Ahadinezhad B, Khadem Haghighian H. Effects of Ellagic Acid on Oxidative Stress Index, Inflammatory Markers and Quality of Life in Patients With Irritable Bowel Syndrome: Randomized Double-blind Clinical Trial. Clin Nutr Res 2022; 11:98-109. [PMID: 35558999 PMCID: PMC9065395 DOI: 10.7762/cnr.2022.11.2.98] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 04/19/2022] [Accepted: 04/20/2022] [Indexed: 11/24/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a common disorder that affects the large intestine. Oxidative stress and inflammation play a major role in IBS. Considering the antioxidant properties of ellagic acid (EA), this study was designed to evaluate the effect of EA on oxidative stress index, inflammatory markers, and quality of life in patients with IBS. This research was conducted as a randomized, double-blind, placebo-controlled clinical trial; 44 patients with IBS were recruited. Patients who met the inclusion criteria were randomly allocated to consume a capsule containing 180 mg of EA per day (n = 22) or a placebo (n = 22) for 8 weeks. Serum levels of total antioxidant capacity (TAC), malondialdehyde (MDA), C-reactive protein (CRP), and interleukin-6 (IL-6) were measured at the beginning and the end of the study. Also, quality of life was assessed using a self-report questionnaire for IBS patients (IBS-QOL). At the end of the study, we saw a significant decrease and increase in the MDA and TAC in the intervention group, respectively (p < 0.05). Also, EA consumption reduced CRP and IL-6 levels, and these changes were significant in comparison with placebo group changes (p < 0.05). The overall score of IBS-QOL significantly decreased, and quality of life was increased (p < 0.05), but there were no significant changes in the placebo group. According to these findings, receiving polyphenols, such as EA, may help maintain intestinal health by modulating inflammation and oxidative stress and ultimately improving the quality of life in IBS patients.
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Affiliation(s)
- Zahra Mirzaie
- Department of Nutrition, School of Health, Qazvin University of Medical Sciences, Qazvin 34197-59811, Iran
| | - Ali Bastani
- Department of Internal Medicine, Velayat Clinical Research Development Unit, Qazvin University of Medical Sciences, Qazvin 34197-59811, Iran
| | - Ali Akbar Haji-Aghamohammadi
- Department of Internal Medicine, Velayat Clinical Research Development Unit, Qazvin University of Medical Sciences, Qazvin 34197-59811, Iran
| | | | - Bahman Ahadinezhad
- Social Determinants of Health Research Center, Qazvin University of Medical Sciences, Qazvin 34197-59811, Iran
| | - Hossein Khadem Haghighian
- Department of Nutrition, School of Health, Qazvin University of Medical Sciences, Qazvin 34197-59811, Iran
- Metabolic Diseases Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin 34197-59811, Iran
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Daye M, Cihan FG, Işık B, Hafızoğlu B. Evaluation of bowel habits in patients with acne vulgaris. Int J Clin Pract 2021; 75:e14903. [PMID: 34553475 DOI: 10.1111/ijcp.14903] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Accepted: 09/19/2021] [Indexed: 12/19/2022] Open
Abstract
PURPOSE To evaluate the bowel habits of patients with acne vulgaris. METHOD In this case-control study, socio-demographical characteristics of the participants (age, gender, marital status, educational status, profession, economic status, smoking-alcohol habits, chronic diseases, previous operations, people they live with and diet) were questioned and the global acne grading scores of the patients were calculated. Bristol Stool Scale, Rome III IBS Criteria, International Physical Activity Questionnaire-Short Form, Hospital Anxiety Depression and KADF (dietary fibre information) scales were completed. RESULTS The patient group consisted of 102 participants and the control group consisted of 104 participants. The mean age was 20.9 ± 3.9 years old in the case group and 21.8 ± 5.0 years old in the control group. Patient and control groups were similar in terms of age and gender. Smoking rates were significantly higher in the patient group (P = .035). The amount of coffee consumed/day was significantly higher in the patient group (P = .040). According to the global acne grading scores, 55.9% (n = 57) had medium, 39.2% (n = 40) had mild, 3.9% (n = 4) had severe and 1% (n = 1) had very severe acne. Anxiety scores were found to be significantly higher in the patient group (P = .005). When the case and control groups were compared for IBS presence, no significant difference was found (P = .317). Also, IBS was not related to acne severity (P = .162). CONCLUSION Further large sample sized studies are needed on this subject, as there is strong evidence about brain-gut-skin axis existence.
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Affiliation(s)
- Munise Daye
- Department of Dermatology, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey
| | - Fatma Gökşin Cihan
- Department of Family Medicine, Necmettin Erbakan University, Konya, Turkey
| | - Begüm Işık
- Department of Dermatology, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey
| | - Berna Hafızoğlu
- Department of Family Medicine, Necmettin Erbakan University, Konya, Turkey
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Mechanism of QingHuaZhiXie Prescription Regulating TLR4-IECs Pathway in the Intervention of Diarrhea Predominant Irritable Bowel Syndrome. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:5792130. [PMID: 34795785 PMCID: PMC8594983 DOI: 10.1155/2021/5792130] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 09/25/2021] [Accepted: 10/25/2021] [Indexed: 12/30/2022]
Abstract
To investigate the effect and mechanism of QingHuaZhiXie prescription on diarrhea predominant irritable bowel syndrome (D-IBS), animal models of rats were used in this study. 48 rats were randomly divided into 6 groups, containing one control group, one animal model group (D-IBS group), and four drug intervention groups (low, medium, and high dosage of QingHuaZhiXie prescription and trimebutine maleate intervention group). Abdominal withdrawal reflex (AWR) and Bristol stool form scale were recorded; the expression levels of inflammatory factors (TNF-α and IFN-γ), pathway proteins TLR4, MyD88, NF-κB, and key proteins of tight junction between intestinal epithelial cells (IECs) were detected; the microstructure of intestinal mucosal was observed by hematoxylin and eosin (H&E) staining; MPO activity was detected with immunohistochemical analysis to reflect the inflammation of tissues. Results show that QingHuaZhiXie prescription reduced diarrhea index and intestinal hypersensitivity and intestinal tissue integrity after intervention. MPO activity in QingHuaZhiXie prescription-treated rats was significantly lower relative to their model group. The expression levels of inflammatory factors and TLR4/MyD88/NF-κB pathway proteins were repressed, and the protein levels of occludin and claudin-1 increased. Meanwhile, this study also found that the remission effect of QingHuaZhiXie prescription on D-IBS increased with its dosage increase. Hence, as a therapeutic prescription for D-IBS, QingHuaZhiXie prescription could relieve D-IBS symptoms through balancing the inflammatory factors expression by inhibiting the TLR4/MyD88/NF-κB pathway and maintaining the function and structure of IECs by improving the protein levels of JAM, occludin, claudin-1, and ZO-1.
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The Association of Irritable Bowel Complaints and Perceived Immune Fitness among Individuals That Report Impaired Wound Healing: Supportive Evidence for the Gut–Brain–Skin Axis. GASTROENTEROLOGY INSIGHTS 2021. [DOI: 10.3390/gastroent12040040] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The gut–brain–skin axis is important in wound healing. The aim of this study was to investigate the association between experiencing irritable bowel syndrome (IBS) symptoms, perceived immune fitness, and impaired wound healing. N = 1942 Dutch students (mean (SD) age 21.3 (2.1), 83.6% women) completed an online survey. They were allocated to one of four groups: (1) control group (N = 1544), (2) wound infection (WI) group (N = 65), (3) slow healing wounds (SHW) group (N = 236), or (4) a combination group (COMBI), which experienced both WI and SHW (N = 87). Participants rated their perceived immune fitness on a scale ranging from very poor (0) to excellent (10), and the severity of IBS symptoms (constipation, diarrhea, and pain) was assessed with the Birmingham IBS Symptom Questionnaire. Compared to the control group, perceived immune fitness was significantly poorer for the SHW group (p < 0.001) and COMBI group (p < 0.001), but not for the WI group. Compared to the control group, constipation was reported significantly more frequently by the SHW group (p < 0.001) and the WI group (p = 0.012), diarrhea was reported significantly more frequent by the SHW group (p = 0.038) and the COMBI group (p = 0.004), and pain was reported significantly more frequent by the SHW group (p = 0.020) and COMBI group (p = 0.001). Correlations between IBS complaints and perceived immune fitness were statistically significant (p < 0.001), and also a highly significant and negative association was found between the percentage of participants that reported impaired wound healing and perceived immune fitness (r = −0.97, p < 0.001). In conclusion, among participants with self-reported impaired wound healing, IBS complaints were significantly more severe, and accompanied by a significantly reduced perceived immune fitness.
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Balan Y, Gaur A, Sakthivadivel V, Kamble B, Sundaramurthy R. Is the Gut Microbiota a Neglected Aspect of Gut and Brain Disorders? Cureus 2021; 13:e19740. [PMID: 34938619 PMCID: PMC8684598 DOI: 10.7759/cureus.19740] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/19/2021] [Indexed: 12/13/2022] Open
Abstract
The gut microbiota is a quickly developing bacterial ecosystem with biodiversity. It is an adaptive immunity that varies with food intake, environmental conditions, and human habits, among other factors. Various external stimuli, such as drugs, can influence the gut microbial environment and lead to gut dysbiosis. Recently, gut dysbiosis has been identified as an important factor that leads to several diseases either by the released metabolites or by the gut neuronal connection. In brain disorders, gut dysbiosis is involved in neuropsychiatric manifestations, including autism spectrum disorder, anxiety, and depression by interfering with neurotransmitter homeostasis, and neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease by releasing abnormal metabolites from the gut. Gut dysbiosis has been documented in gut disorders, including inflammatory bowel disease or irritable bowel syndrome. Immune cells in the gut are modulated by external factors such as stress, diet, and drugs to produce inflammatory cytokines, including interleukins (IL-4, IL-6, IL-17, IL-23, etc.). Inflammatory cytokines lead to a cascade of events, which lead to various ailments in the bowel. Beneficial bacteria in the form of probiotics ameliorate the condition and have healthful effects in disease conditions. This warrants further research to identify newer therapeutic strategies for diseases that cannot be cured or are difficult to treat.
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Affiliation(s)
- Yuvaraj Balan
- Department of Biochemistry, All India Institute of Medical Sciences, Bibinagar, Bibinagar, IND
| | - Archana Gaur
- Department of Physiology, All India Institute of Medical Sciences, Bibinagar, Bibinagar, IND
| | | | - Bhushan Kamble
- Department of Community and Family Medicine, All India Institute of Medical Sciences, Bibinagar, Bibinagar, IND
| | - Raja Sundaramurthy
- Department of Microbiology, All India Institute of Medical Sciences, Bibinagar, Bibinagar, IND
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Sugiyama T, Shiotani A. The Cutting Edge Research of Functional Gastrointestinal Disorders in Japan: Review on JGA Core Symposium 2018-2020. Digestion 2021; 102:6-11. [PMID: 33080599 DOI: 10.1159/000510680] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 07/29/2020] [Indexed: 02/04/2023]
Abstract
Highly impacted articles on functional gastrointestinal (GI) disorders research presented at the core symposium held in the Japanese Gastroenterological Association (JGA) annual meeting 2018-2020 are selected and summarized. Regarding visceral hypersensitivity and sensor in GI tracts, transient receptor potential vanilloid 4 ion channel and acid-sensitive ion channel were candidates for hypersensitivity in GI tracts. ATP release from vesicular nucleotide transporter may be a key pathway to sensitize the nerve endings. Regarding inflammation and mucosal immune responses, patients infected with H. pylori having Ser70 type single nucleotide polymorphism of NapA gene was associated with H. pylori-related dyspepsia via gastric dysmotility. Gastric histology infected with Ser70 type NapA was shown severe infiltration of neutrophils into intramuscular layer. Macrophages, mast cells, and neutrophils are infiltrated in the colon of irritable bowel syndrome (IBS) patients and the locally produced IL-1β upregulated brain-derived neurotrophic factor (BDNF) in enteric glia cells. BDNF can also stimulate nerve endings and might be linked to pain in the colon. Dysbiosis in the composition of commensal bacteria communities is associated with the pathogenesis of various diseases including IBS and gut-brain interaction. The investigation on the mucosa-associated microbiota (MAM) is essential for understanding the interactions. The α-diversity and β-diversity of MAM indices are significantly different among IBS-D, IBS-C, and controls, and the different diversity might contribute to the pathophysiology of IBS. As research works on psychosocial factors show, maternal separation animal model was used and it is early life stress. The stress had induced colonic hyper-contraction, gastric hypersensitivity, and delayed emptying. The precise molecular mechanisms are still under investigations.
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Affiliation(s)
- Toshiro Sugiyama
- Research Division of Molecular Targeting Therapy and Prevention of GI Cancer, Hokkaido University Hospital, Sapporo, Japan,
| | - Akiko Shiotani
- Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan
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Elbadawi M, Ammar RM, Aziz-Kalbhenn H, Rabini S, Klauck SM, Dawood M, Saeed MEM, Kampf CJ, Efferth T. Anti-inflammatory and tight junction protective activity of the herbal preparation STW 5-II on mouse intestinal organoids. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 88:153589. [PMID: 34111617 DOI: 10.1016/j.phymed.2021.153589] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 04/17/2021] [Accepted: 04/29/2021] [Indexed: 06/12/2023]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a functional bowel disorder, in which recurrent abdominal pain is associated with defecation or a change in bowel habits. STW 5-II is a combination of six medicinal herbs with a clinically proven efficacy in managing IBS. AIM This study aims to establish an in vitro IBS model using mouse intestinal organoids and to explore the anti-inflammatory and tight junction protective activities of the multi-herbal preparation STW 5-II. METHODS Intestinal organoids were cultured in 1:1 Matrigel™ and medium domes. Inflammation and tight junction disruption were induced by a cocktail of cytokines (TNFα, IFNγ, IL-1β, IL-6) and bacterial proteins (LPS, flagellin). Organoids were treated with different concentrations of STW 5-II, and its multi-target activity was assessed using microarray analyses, RT-qPCR, immunofluorescence, western blot, immunohistochemistry, and a FITC permeability assay. In addition, we analyzed the expression of pNF-κB, pSTAT1, iNOS and ZO-1. In silico analyses were conducted to predict and identify the active components that may be responsible in mediating the multi-target anti-inflammatory activity of STW 5-II. RESULTS An organoid based IBS model was successfully established. STW 5-II effectively reduced the cytokines-induced overexpression of the pro-inflammatory mediators pNF-κB, pSTAT1 and iNOS. Moreover, STW 5-II attenuated cytokine-mediated downregulation of the tight junction protein, ZO-1. This finding was confirmed by a FITC permeability assay. In silico analyses revealed a promising inhibitory activity of some isolated compounds from STW 5-II against NF-κB, STAT1 and iNOS. CONCLUSION STW 5-II possesses multiple anti-inflammatory as well as tight junction protective activities that could explain its clinically proven efficacy in managing IBS symptoms.
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Affiliation(s)
- Mohamed Elbadawi
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany
| | - Ramy M Ammar
- Bayer Consumer Health, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany
| | - Heba Aziz-Kalbhenn
- Bayer Consumer Health, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany
| | - Sabine Rabini
- Bayer Consumer Health, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany
| | - Sabine M Klauck
- Division of Cancer Genome Research, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Mona Dawood
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany; Department of Molecular Biology, Faculty of Medical Laboratory Science, Al-Neelain University, Khartoum, Sudan
| | - Mohamed E M Saeed
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany
| | | | - Thomas Efferth
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
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