1
|
Zheng H, Chen Y, Lu S, Liu Z, Ma Y, Zhang C, Zhang Y, Zhang J, Liu C, Chu M, Pei F, Liu S, Duan L. Mechanosensory Piezo2 regulated by gut microbiota participates in the development of visceral hypersensitivity and intestinal dysmotility. Gut Microbes 2025; 17:2497399. [PMID: 40296251 PMCID: PMC12045567 DOI: 10.1080/19490976.2025.2497399] [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: 06/25/2024] [Revised: 01/23/2025] [Accepted: 04/17/2025] [Indexed: 04/30/2025] Open
Abstract
The gut microbiota plays a crucial role in the manifestation of intestinal dysfunction associated with irritable bowel syndrome (IBS). The mechanosensory Piezo2 has been implicated in the regulation of intestinal function. However, it remains unclear whether Piezo2 is modulated by the gut microbiota, thus contributing to the development of visceral hypersensitivity and gut dysmotility. The study enrolled patients with diarrhea-predominant IBS (IBS-D) alongside healthy controls (HC). Questionnaires, rectal barostat test, and colonoscopy with mucosal biopsy were conducted. Fecal microbiota transplantation (FMT) was performed using samples from HC or IBS-D patients, and interventions with Akkermansia muciniphila or Fusobacterium varium were carried out on colon- or dorsal root ganglion (DRG)- Piezo2 knockdown pseudo-germ-free mice. Visceral sensitivity and intestinal motility were assessed. Piezo2 levels were detected using western blot and immunofluorescence. Fecal 16S rRNA sequencing and cecum untargeted metabolomics analysis, followed by molecular docking predictions of Piezo2, were also performed. The ratio of Piezo2+/5-HT+ cells was lower in IBS-D patients, positively correlated with visceral sensation and intestinal dysbiosis. The mice that received FMT from IBS-D patients exhibited colonic dysmotility and visceral hypersensitivity, along with elevated Piezo2 protein levels in the colon and DRG. Knockdown of Piezo2 in the colon or DRG ameliorated the FMT-induced colonic dysmotility and visceral hypersensitivity. Fecal 16S rRNA sequencing revealed distinct microbiota composition. Notably, Fusobacterium varium, but not Akkermansia muciniphila, induced gut dysmotility and visceral hypersensitivity, effects that could be alleviated by colon or DRG Piezo2 knockdown. Additionally, Fusobacterium varium lead to increased Piezo2 protein levels, as well as elevated levels of indole-3-acetic acid and indole-3-acrylic acid, which were predicted to bind to Piezo2, causing disturbances. Piezo2 can be regulated by gut microbiota and involved in visceral hypersensitivity and colonic dysmotility, with Fusobacterium varium playing a crucial role.
Collapse
Affiliation(s)
- Haonan Zheng
- Department of Gastroenterology, Peking University Third Hospital, Beijing, P. R. China
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal Diseases, Peking University Third Hospital, Beijing, P. R. China
- PKUMed-EKEMed Joint Laboratory for Human Microbiome Research, Peking University Health Science Center, Beijing, P. R. China
| | - Yuzhu Chen
- Department of Gastroenterology, Peking University Third Hospital, Beijing, P. R. China
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal Diseases, Peking University Third Hospital, Beijing, P. R. China
- PKUMed-EKEMed Joint Laboratory for Human Microbiome Research, Peking University Health Science Center, Beijing, P. R. China
| | - Siqi Lu
- Department of Gastroenterology, Peking University Third Hospital, Beijing, P. R. China
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal Diseases, Peking University Third Hospital, Beijing, P. R. China
| | - Zuojing Liu
- Department of Gastroenterology, Peking University Third Hospital, Beijing, P. R. China
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal Diseases, Peking University Third Hospital, Beijing, P. R. China
| | - Yinchao Ma
- Department of Immunology, NHC Key Laboratory of Medical Immunology, School of Basic Medical Sciences, Peking University, Beijing, P. R. China
| | - Cunzheng Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, P. R. China
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal Diseases, Peking University Third Hospital, Beijing, P. R. China
- PKUMed-EKEMed Joint Laboratory for Human Microbiome Research, Peking University Health Science Center, Beijing, P. R. China
| | - Yiming Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, P. R. China
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal Diseases, Peking University Third Hospital, Beijing, P. R. China
| | - Jindong Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, P. R. China
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal Diseases, Peking University Third Hospital, Beijing, P. R. China
- PKUMed-EKEMed Joint Laboratory for Human Microbiome Research, Peking University Health Science Center, Beijing, P. R. China
| | - Chang Liu
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao, P. R. China
| | - Ming Chu
- Department of Immunology, NHC Key Laboratory of Medical Immunology, School of Basic Medical Sciences, Peking University, Beijing, P. R. China
| | - Fei Pei
- Department of Pathology, Peking University Third Hospital; School of Basic Medical Sciences, Peking University, Beijing, P. R. China
| | - Shuangjiang Liu
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao, P. R. China
- State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P. R. China
| | - Liping Duan
- Department of Gastroenterology, Peking University Third Hospital, Beijing, P. R. China
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal Diseases, Peking University Third Hospital, Beijing, P. R. China
- PKUMed-EKEMed Joint Laboratory for Human Microbiome Research, Peking University Health Science Center, Beijing, P. R. China
| |
Collapse
|
2
|
Alver SK, Peters BA, Mossavar-Rahmani Y, Qi Q, McClain AC, Van Horn L, Burk RD, Kaplan RC. Association of meal timing with adiposity measures and gut microbiome characteristics in a cohort study: the Hispanic Community Health Study/Study of Latinos. Am J Clin Nutr 2025:S0002-9165(25)00189-3. [PMID: 40222449 DOI: 10.1016/j.ajcnut.2025.04.003] [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: 09/30/2024] [Revised: 03/14/2025] [Accepted: 04/07/2025] [Indexed: 04/15/2025] Open
Abstract
BACKGROUND Time-restricted eating may help control weight through caloric restriction, circadian rhythm, or influence on the gut microbiome (GMB). Physical activity (PA) also plays a role, as people with a longer eating window (EW, time between first and last daily intake) may be more active. The associations between meal timing, adiposity, PA, sedentary behavior (SB), and GMB characteristics are of interest in Hispanic/Latino persons, who experience a high burden of cardiometabolic diseases. OBJECTIVES We explored the relationship of EW with energy intake and accelerometer-measured activity and assessed whether a longer EW and later midpoint of intake (MOI, midpoint time of intake) are associated with adiposity and GMB differences in Hispanic/Latino adults. METHODS Using data from the prospective Hispanic Community Health Study/Study of Latinos (n = 11,778 participants with valid 24-h dietary recall and accelerometer data, no unplanned weight loss, and BMI ≥ 18.5 kg/m2; n = 1925 with GMB data), we explored the relationship between EW, SB, and energy intake. We used multivariable linear regression models to study the relationship between EW or MOI and adiposity measures and GMB characteristics, adjusted for clinical, behavioral, and demographic characteristics. RESULTS Those with longer EW tended to have less SB and greater energy intake, suggesting that some individuals may balance greater intake with greater expenditure. After adjustments including energy balance, each hour of EW was associated with 0.29% higher BMI (95% confidence interval [CI]: 0.07, 0.51; P = 0.011). Longer EW and caloric EW (EWC, EW, caloric meals only) were associated with several obesity-associated GMB taxa, such as Streptococcus (enriched, β: 0.04; 95% CI: 0.01, 0.07, for EW). MOI was not significantly associated with adiposity or GMB characteristics. CONCLUSIONS Shorter EW may promote healthy weight, but some individuals with longer compared with shorter EWs tend to have greater activity that could balance their greater energy intake. EW and EWC may influence GMB characteristics.
Collapse
Affiliation(s)
- Sarah K Alver
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
| | - Brandilyn A Peters
- Departments of Epidemiology and Population Health, Pediatrics, Microbiology & Immunology, and Obstetrics, Gynecology & Women's Health, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Yasmin Mossavar-Rahmani
- Departments of Epidemiology and Population Health, Pediatrics, Microbiology & Immunology, and Obstetrics, Gynecology & Women's Health, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Qibin Qi
- Departments of Epidemiology and Population Health, Pediatrics, Microbiology & Immunology, and Obstetrics, Gynecology & Women's Health, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Amanda C McClain
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, CA, United States
| | - Linda Van Horn
- Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Robert D Burk
- Departments of Epidemiology and Population Health, Pediatrics, Microbiology & Immunology, and Obstetrics, Gynecology & Women's Health, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Robert C Kaplan
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, United States; Departments of Epidemiology and Population Health, Pediatrics, Microbiology & Immunology, and Obstetrics, Gynecology & Women's Health, Albert Einstein College of Medicine, Bronx, NY, USA.
| |
Collapse
|
3
|
Chen H, Fang J, Liu S, Gao S, Shi H, Ma JZ, Shen X, Wang W, Liu Z. Efficacy and safety of two-step acupuncture therapy for symptom relief in adults with mild to moderate ulcerative colitis: rationale and design of the TSA-UC randomised controlled trial. BMJ Open 2025; 15:e094301. [PMID: 40021194 PMCID: PMC11873345 DOI: 10.1136/bmjopen-2024-094301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 02/14/2025] [Indexed: 03/03/2025] Open
Abstract
INTRODUCTION Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterised by episodes of symptoms including rectal bleeding, increased stool frequency and abdominal pain, impacting quality of life significantly. Conventional treatments often come with potential side effects and may not be sufficient. Acupuncture is increasingly recognised for its potential benefits in UC. This study aims to assess the efficacy and safety of acupuncture for symptom relief in mild to moderate UC. METHODS AND ANALYSIS This single-centre, parallel-arm, randomised, sham-controlled, the two-step acupuncture (TSA)-UC trial, will involve 64 adults with mild to moderate UC, randomly assigned in a 1:1 ratio to either the acupuncture or sham acupuncture group. Participants will receive 20 sessions of two-step acupuncture or sham acupuncture therapy over 8 weeks. Blinding will be applied to participants, outcome assessors and statisticians. The primary outcome measure is the change in Patient-Reported Outcome 2 (PRO2) from baseline at week 8. Secondary outcomes include changes from baseline in the following scales: PRO2 at other time points, weekly average Numeric Rating Scale (NRS) for bowel urgency, weekly average NRS for abdominal pain (both associated and not associated with bowel movement), the 32-item Inflammatory Bowel Disease Questionnaire, Work Productivity and Activity Impairment Questionnaire-IBD, Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale. The Patient Global Impression of Change will also be assessed. Long-term effects of acupuncture will be explored. Adverse events and additional treatments will be monitored throughout the study. The modified intention-to-treat population including participants who complete baseline assessments and receive at least one treatment session will be analysed. ETHICS AND DISSEMINATION The study has received ethical approval from the Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences (2024-190-KY). The results will be published in a peer-reviewed medical journal. TRIAL REGISTRATION NUMBER NCT06615765.
Collapse
Affiliation(s)
- He Chen
- Department of Acupuncture, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jiufei Fang
- Department of Acupuncture, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Sixing Liu
- Beijing University of Chinese Medicine, Beijing, China
| | - Shuai Gao
- Department of Acupuncture, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hangyu Shi
- School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
| | - Ji-Zheng Ma
- Department of Gastroenterology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xinyu Shen
- Beijing University of Chinese Medicine, Beijing, China
| | - Weiming Wang
- Department of Acupuncture, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zhishun Liu
- Department of Acupuncture, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| |
Collapse
|
4
|
Agarwal P, Jha BK, Somagoni J, B SS, Modh V, Chakilam SK, Kumar V, Vasantrao MS, Kalla M, Kavitha A, Goyal O, Bhatia A. Efficacy and safety of elobixibat in patients with chronic constipation-A randomized, multicenter, double-blind, placebo-controlled, parallel-group study from India. Indian J Gastroenterol 2025:10.1007/s12664-024-01719-7. [PMID: 39985701 DOI: 10.1007/s12664-024-01719-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 11/21/2024] [Indexed: 02/24/2025]
Abstract
BACKGROUND Elobixibat is a locally acting ileal bile acid transporter (IBAT) inhibitor that relieves functional constipation in patients by accelerating colonic transit. In this study, we aimed at determining the efficacy and safety of elobixibat for short-term treatment (two weeks) of chronic constipation in Indian patients. METHODS The present study was a randomized, double-blind, parallel-group, placebo-controlled, phase III study to evaluate efficacy and safety of elobixibat. The study planned to enroll patients with chronic constipation of at least six months' duration, satisfying Rome IV criteria for functional constipation. Following a run-in of approximately 14 days to confirm eligibility and determine baseline frequency of spontaneous bowel movements (SBMs), eligible patients were randomized 1:1 either to elobixibat or to placebo groups. The change in weekly frequency of spontaneous bowel movements (SBMs) at the end of treatment (week two) over baseline was the primary efficacy endpoint in this trial. Primary efficacy analyses were based on the modified intention-to-treat (mITT) population. This trial is registered at CTRI (Clinical Trial Registry of India). RESULTS Between April 2023 and December 2023, 150 patients were randomized into the two-week trial. In mITT population (n = 146 [elobixibat = 75 and placebo = 71]), the least square mean (LSM) difference between elobixibat (3.83) and placebo (2.68) was 1.15 (95% CI, 0.31, 1.99) demonstrating a statistically significant improvement (p = 0.008) in weekly frequency of SBMs (week two over baseline) with the use of elobixibat. The proportions of patients with a complete spontaneous bowel movement (CSBM) "response" was significantly higher with elobixibat (49.33%) compared to the placebo (26.76%) treatment (difference 22.57% [95% CI, 8.36%, 36.78%] [p = 0.005]). The most common adverse event (AE) was abdominal pain (elobixibat = 6 patients [7.89%] vs. placebo = 3 patients [4.05%]). CONCLUSIONS Elobixibat was well tolerated and improved bowel movement frequency within two weeks of treatment in Indian patient population with chronic constipation. CLINICAL TRIAL REGISTRY NUMBER CTRI/2022/10/046690.
Collapse
Affiliation(s)
- Piyush Agarwal
- Global Clinical Management, Dr. Reddy's Laboratories Pvt. Ltd, Hyderabad, 500 016, India.
| | - Brajesh Kumar Jha
- Global Clinical Management, Dr. Reddy's Laboratories Pvt. Ltd, Hyderabad, 500 016, India
| | - Jaganmohan Somagoni
- Global Clinical Management, Dr. Reddy's Laboratories Pvt. Ltd, Hyderabad, 500 016, India
| | - Srinivas Shenoy B
- Global Clinical Management, Dr. Reddy's Laboratories Pvt. Ltd, Hyderabad, 500 016, India
| | - Vipul Modh
- Global Clinical Management, Dr. Reddy's Laboratories Pvt. Ltd, Hyderabad, 500 016, India
| | - Sanketh Kumar Chakilam
- Global Clinical Management, Dr. Reddy's Laboratories Pvt. Ltd, Hyderabad, 500 016, India
| | - Vinay Kumar
- GSVM Medical College, Kanpur, 208 002, India
| | | | - Mukesh Kalla
- S.R. Kalla Memorial Gastro and General Hospital, Jaipur, 302 006, India
| | | | - Omesh Goyal
- Dayanand Medical College and Hospital, Ludhiana, 141 001, India
| | - Ashima Bhatia
- Global Clinical Management, Dr. Reddy's Laboratories Pvt. Ltd, Hyderabad, 500 016, India
| |
Collapse
|
5
|
Kansu A, Kutluk G, Caltepe G, Arikan C, Urganci N, Tumgor G, Yuce A, Tuna Kirsaclioglu C, Demir AM, Demirbas F, Usta M, Yavuz S, Demirtas Guner D, Gumus E, Dalgic B, Dogan Y, Gerenli N, Kocamaz H, Gulerman F, Sag E, Alptekin Sarioglu A, Eksi Bozbulut N, Teker Duztas D, Altug Demirol H, Celtik C, Gungor O, Demiroren K, Uncuoglu Aydogan A, Bekem O, Arslan Z, Cakir M, Ekici A, Uyar Aksu N, Ecevit C, Erdogan S. Use of a specialized peptide-based enteral formula containing medium-chain triglycerides for enteral tube feeding in children with cerebral palsy and previous tube feeding intolerance on standard enteral formula: a prospective observational TolerUP study. Front Pediatr 2025; 13:1448507. [PMID: 40013110 PMCID: PMC11861557 DOI: 10.3389/fped.2025.1448507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 01/15/2025] [Indexed: 02/28/2025] Open
Abstract
Objective Use of peptide-based formulas supplemented with medium chain triglycerides (MCTs) is considered a beneficial strategy to decrease the tube-feeding associated gastrointestinal tolerance. In children with cerebral palsy (CP), overall effects of enteral tube feeding as well as the utility of peptide-based specialized enteral formulas in those with gastrointestinal intolerance have not been extensively studied. This study aimed to evaluate the utility of enteral tube feeding via specialized peptide-based formula containing MCTs in children with CP in terms of gastrointestinal intolerance, anthropometrics, defecation characteristics and parental satisfaction with enteral formula. Methods Children with CP who received enteral tube feeding via specialized peptide-based formula containing MCTs were included in this prospective observational study. Anthropometrics (z scores for weight for age [WFA], weight for height [WFH], triceps skinfold thickness [TSFT] and mid-upper arm circumference [MUAC]), gastrointestinal intolerance symptoms, defecation frequency and stool patterns and formula satisfaction were recorded at baseline and during 6-month follow up. Results A total of 96 children with CP (mean ± SD age: 5.6 ± 3.2 years, 56.3% were boys) were included. Significant improvements were noted in MUAC, TSFT and WFH z scores at the 6th month visit. The rate of "severe symptoms" and the likelihood of Type-1/Type-2 (constipation) stool pattern were significantly decreased. Majority of parents were satisfied with the study formula. Conclusion Our findings revealed favorable efficacy and safety of using a specialized peptide-based formula containing MCT in provision of enteral tube feeding among children with CP in terms of improved anthropometrics, amelioration of gastrointestinal intolerance symptoms and normalization of bowel movements along with a high parental satisfaction.
Collapse
Affiliation(s)
- Aydan Kansu
- Department of Pediatric Gastroenterology, Ankara University School of Medicine, Ankara, Türkiye
| | - Gunsel Kutluk
- Department of Pediatric Gastroenterology, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Türkiye
| | - Gonul Caltepe
- Department of Pediatric Gastroenterology, Ondokuz Mayis University Faculty of Medicine, Samsun, Türkiye
| | - Cigdem Arikan
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Koc University Faculty of Medicine, Istanbul, Türkiye
| | - Nafiye Urganci
- Department of Pediatric Gastroenterology, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Türkiye
| | - Gokhan Tumgor
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cukurova University Faculty of Medicine, Adana, Türkiye
| | - Aysel Yuce
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Hacettepe University Faculty of Medicine, Ankara, Türkiye
| | - Ceyda Tuna Kirsaclioglu
- Department of Pediatric Gastroenterology, Ankara University School of Medicine, Ankara, Türkiye
| | - Arzu Meltem Demir
- Department of Pediatric Gastroenterology, Ankara City Hospital, Ankara, Türkiye
| | - Fatma Demirbas
- Department of Pediatric Gastroenterology, Ondokuz Mayis University Faculty of Medicine, Samsun, Türkiye
| | - Merve Usta
- Department of Pediatric Gastroenterology, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Türkiye
| | - Sibel Yavuz
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cukurova University Faculty of Medicine, Adana, Türkiye
| | - Duygu Demirtas Guner
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Hacettepe University Faculty of Medicine, Ankara, Türkiye
| | - Ersin Gumus
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Hacettepe University Faculty of Medicine, Ankara, Türkiye
| | - Buket Dalgic
- Department of Pediatric Gastroenterology, Gazi University Faculty of Medicine, Ankara, Türkiye
| | - Yasar Dogan
- Department of Pediatric Gastroenterology, Firat University Faculty of Medicine, Elazig, Türkiye
| | - Nelgin Gerenli
- Department of Pediatric Gastroenterology, Istanbul Umraniye Training and Research Hospital, Istanbul, Türkiye
| | - Halil Kocamaz
- Department of Pediatrics, Division of Pediatric Gastroenterology, Pamukkale University Faculty of Medicine, Denizli, Türkiye
| | - Fulya Gulerman
- Department of Pediatric Gastroenterology, Kirikkale University Faculty of Medicine, Kirikkale, Türkiye
| | - Elif Sag
- Department of Pediatric Gastroenterology Hepatology and Nutrition, Karadeniz Technical University Faculty of Medicine, Trabzon, Türkiye
| | | | - Neslihan Eksi Bozbulut
- Department of Pediatric Gastroenterology, Gazi University Faculty of Medicine, Ankara, Türkiye
| | - Demet Teker Duztas
- Department of Pediatric Gastroenterology, Gazi University Faculty of Medicine, Ankara, Türkiye
| | - Hatice Altug Demirol
- Department of Pediatric Gastroenterology, Firat University Faculty of Medicine, Elazig, Türkiye
| | - Coskun Celtik
- Department of Pediatric Gastroenterology, Istanbul Umraniye Training and Research Hospital, Istanbul, Türkiye
| | - Olcay Gungor
- Department of Pediatrics, Division of Pediatric Gastroenterology, Pamukkale University Faculty of Medicine, Denizli, Türkiye
| | - Kaan Demiroren
- Department of Pediatric Gastroenterology, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Türkiye
| | - Aysen Uncuoglu Aydogan
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Kocaeli University Faculty of Medicine, Kocaeli, Türkiye
| | - Ozlem Bekem
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Health Sciences Dr. Behcet Uz Children's Hospital, Izmir, Türkiye
| | - Zeynep Arslan
- Department of Pediatric Gastroenterology, Kirikkale University Faculty of Medicine, Kirikkale, Türkiye
| | - Murat Cakir
- Department of Pediatric Gastroenterology Hepatology and Nutrition, Karadeniz Technical University Faculty of Medicine, Trabzon, Türkiye
| | - Arzu Ekici
- Department of Pediatric Neurology, Bursa Yuksek Ihtisas Training and Research Hospital, Bursa, Türkiye
| | - Nihal Uyar Aksu
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Kocaeli University Faculty of Medicine, Kocaeli, Türkiye
| | - Cigdem Ecevit
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Health Sciences Dr. Behcet Uz Children's Hospital, Izmir, Türkiye
| | | |
Collapse
|
6
|
Chen Y, Ding M. Novel insights into carbohydrate-to-fiber ratio and constipation: NHANES findings suggest a turning point. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2025. [PMID: 39784686 DOI: 10.17235/reed.2024.10306/2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
Abstract
BACKGROUND Constipation, a widespread global issue, prompted an investigation into the intricate relationship between dietary factors and this condition. This study delves into the association between carbohydrate-to-fiber (CF) ratio and constipation, employing data from the National Health and Nutrition Examination Survey (NHANES) and a comprehensive meta-analysis. METHODS Utilizing NHANES data (2005-2010) from 7752 adults, constipation was defined based on stool type (Bristol Stool Form Scale types 1 or 2). The CF ratio was calculated, revealing an L-shaped, non-linear association with constipation. A meta-analysis of 16 studies (1626 participants) confirmed a positive effect of dietary fiber on constipation, emphasizing the robustness of the findings. RESULTS Among participants, constipation prevalence stood at 13.98%. The CF ratio exhibited a turning point at 26.92/day, with adjusted odds ratios for constipation indicating a decrease with higher CF ratios. Meta-analysis results supported these findings, demonstrating a significant positive effect of dietary fiber on constipation. CONCLUSION This study illuminates a nuanced relationship between CF ratio and constipation, suggesting a critical turning point at 26.92/day. These findings underscore the importance of dietary assessment, offering valuable insights for clinicians and individuals. Further prospective research is warranted to validate the CF ratio as a robust dietary assessment tool.
Collapse
Affiliation(s)
- Yin Chen
- Proctology, The Affiliated Xuancheng Hospital of Wannan Medical College
| | - Meisheng Ding
- Proctology, The Affiliated Xuancheng Hospital of Wannan Medica, china
| |
Collapse
|
7
|
Park CJ, Jones MP, Prott G, Sequeira C, Malcolm A. Rome IV Functional Defecation Disorder: Time for a Change in Symptom Criteria for Improved Clinical Relevance? Am J Gastroenterol 2024:00000434-990000000-01504. [PMID: 39787361 DOI: 10.14309/ajg.0000000000003267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 12/11/2024] [Indexed: 01/12/2025]
Abstract
INTRODUCTION Defecatory disorders are common affecting up to 8% of the population. Rome IV diagnostic criteria are used to define this condition and, therefore, select patients for the gold standard therapy, anorectal biofeedback. The aim of this study was to test the current Rome IV Functional Defecation Disorder (FDD) criteria in a real-world population by using the response to biofeedback as a validation tool. METHODS A total of 485 patients (female 437, mean age 50 ± 17.6 years) with defecatory symptoms presenting to a neurogastroenterology clinic underwent anorectal biofeedback therapy regardless of whether they met formal Rome IV FDD criteria or not. Patients were assessed extensively with the Rome questionnaire, constipation questionnaire, and visual analog scales for satisfaction, control, quality of life, and anorectal manometry. RESULTS Rome IV FDD was no better at predicting response to biofeedback compared with non-Rome IV FDD ( P = NS). Digitation ( P = 0.043) and increasing cumulative number of defecatory symptoms ( P = 0.038) were correlated with improvement in biofeedback (≥2-point increase in bowel satisfaction). Those with abnormal physiology only responded well to biofeedback (83% response rate), but this was not statistically different from no Rome IV physiology patients (73%). There was a trend for increasing cumulative number of abnormal physiology factors to correlate with biofeedback ( P = 0.086). DISCUSSION Rome IV symptom criteria need revision to include more defecatory symptoms, include all subtypes of irritable bowel syndrome, and be inclusive of those with either loose stools or more frequent stools such as those previously labeled with "pseudodiarrhea" or "hyperdefecation." Continuing to include physiology criteria in the Rome diagnosis of FDD seems valid.
Collapse
Affiliation(s)
- Calvin Joomann Park
- Faculty of Medicine and Health, University of Sydney, Camperdown, Australia
- Neurogastroenterology Unit and Department of Gastroenterology, Royal North Shore Hospital, St Leonards, Australia
| | - Michael P Jones
- School of Psychological Sciences, Macquarie University, Sydney, Australia
| | - Gillian Prott
- Neurogastroenterology Unit and Department of Gastroenterology, Royal North Shore Hospital, St Leonards, Australia
| | - Carol Sequeira
- Neurogastroenterology Unit and Department of Gastroenterology, Royal North Shore Hospital, St Leonards, Australia
| | - Allison Malcolm
- Faculty of Medicine and Health, University of Sydney, Camperdown, Australia
- Neurogastroenterology Unit and Department of Gastroenterology, Royal North Shore Hospital, St Leonards, Australia
| |
Collapse
|
8
|
Lu S, Chen Y, Guo H, Liu Z, Du Y, Duan L. Differences in clinical manifestations and the fecal microbiome between irritable bowel syndrome and small intestinal bacterial overgrowth. Dig Liver Dis 2024; 56:2027-2037. [PMID: 39043536 DOI: 10.1016/j.dld.2024.07.011] [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: 01/15/2024] [Revised: 07/04/2024] [Accepted: 07/06/2024] [Indexed: 07/25/2024]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) share similar abdominal symptoms; however, their differentiation remains controversial. AIMS To illustrate the differences between the two conditions. METHODS Patients and healthy controls completed questionnaires and provided stool samples for analysis. RESULTS IBS presented with the most severe symptoms and was specifically characterized by intense abdominal pain and frequent episodes of diarrhea. Patients with IBS displayed more dysregulated taxonomy within the fecal microbiota than SIBO. Opportunistic pathogens, including Lachnoclostridium, Escherichia-Shigella, and Enterobacter were enriched in the IBS group which contributed to increased bacterial pathogenicity and positively correlated with abdominal pain and bloating, meanwhile, Lachnoclostridium and Escherichia-Shigella were found to be associated with metabolites affiliated to bile acids, alcohols and derivatives. Bacteria enriched in SIBO group correlated with constipation. The bacterial co-occurrence network within the SIBO group was the most intricate. Ruminococcaceae Group were defined as core bacteria in SIBO. Differential metabolites affiliated to androstane steroids and phenylacetic acids were associated with core bacteria. CONCLUSIONS Our study elucidates the differences between IBS and SIBO in terms of symptoms, microbiota and functions, which provides insights into a better understanding of both diseases and evidence for different treatment strategies.
Collapse
Affiliation(s)
- Siqi Lu
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Yuzhu Chen
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Huaizhu Guo
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Zuojing Liu
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Yanlin Du
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Liping Duan
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China.
| |
Collapse
|
9
|
Esfand SM, Querdasi FR, Gancz NN, Savoca PW, Nussbaum S, Somers JA, Ditzer J, Figueroa MB, Chu K, Towner E, Callaghan BL. The mind, brain, and body study: A protocol for examining the effects of the gut-brain-immune axis on internalizing symptoms in youth exposed to caregiving-related early adversity. Brain Behav Immun Health 2024; 42:100880. [PMID: 39881818 PMCID: PMC11776082 DOI: 10.1016/j.bbih.2024.100880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 09/25/2024] [Accepted: 09/29/2024] [Indexed: 01/31/2025] Open
Abstract
Experiences of caregiving-related adversity are common and one of the strongest predictors of internalizing psychopathology (i.e., anxiety and depression). Specifically, individuals who have been exposed to such early adversities have altered affective neurodevelopment, impaired memory systems, increased risk of developing internalizing disorders, greater inflammation, and differences in gastrointestinal (gut) microbiome composition. Crucially, the gut microbiome undergoes a sensitive period of development that precedes neural and immune sensitive periods, thus making it a potentially fruitful target for intervention. Though previous work has assessed neural, immune, and gut microbiome systems in individuals exposed to early adversity, studies have primarily looked at these biological systems independently. The Mind, Brain, and Body study (MBB) implements multimodal and longitudinal design to assess how changes in the gut microbiome following caregiving-related adversity may underlie altered affective neurodevelopment, memory, and immune functioning in youth and contribute to internalizing symptoms. Across three waves, spread approximately 12-18 months apart, youth with and without previous experiences of caregiving-related adversity completed self-report measures of mental and physical health, provided stool, saliva, hair, and blood samples, and completed an MRI scan. Results of this study will expand our knowledge on how the gut microbiome shapes several biological and cognitive systems and motivate future work investigating the gut microbiome as potential target for intervention.
Collapse
Affiliation(s)
- Shiba M. Esfand
- Department of Psychology, University of California, Los Angeles, 502 Portola Plaza, Los Angeles, CA, 90095, USA
| | - Francesca R. Querdasi
- Department of Psychology, University of California, Los Angeles, 502 Portola Plaza, Los Angeles, CA, 90095, USA
| | - Naomi N. Gancz
- Department of Psychology, University of California, Los Angeles, 502 Portola Plaza, Los Angeles, CA, 90095, USA
| | - Paul W. Savoca
- Department of Psychology, University of California, Los Angeles, 502 Portola Plaza, Los Angeles, CA, 90095, USA
| | - Siyan Nussbaum
- Department of Psychology, University of California, Los Angeles, 502 Portola Plaza, Los Angeles, CA, 90095, USA
| | - Jennifer A. Somers
- Department of Psychology, University of California, Los Angeles, 502 Portola Plaza, Los Angeles, CA, 90095, USA
- Department of Psychological Sciences, Auburn University, 111 Thach Hall, Auburn, AL, 36849, USA
| | - Julia Ditzer
- Department of Psychology, Clinical Child and Adolescent Psychology, Technische Universität Dresden, Dresden, Germany
| | - Matthew B. Figueroa
- Department of Psychology, University of California, Los Angeles, 502 Portola Plaza, Los Angeles, CA, 90095, USA
| | - Kristen Chu
- Department of Psychology, University of California, Los Angeles, 502 Portola Plaza, Los Angeles, CA, 90095, USA
| | - Emily Towner
- Department of Psychology, University of California, Los Angeles, 502 Portola Plaza, Los Angeles, CA, 90095, USA
- Department of Psychology, University of Cambridge, Cambridge, United Kingdom
| | - Bridget L. Callaghan
- Department of Psychology, University of California, Los Angeles, 502 Portola Plaza, Los Angeles, CA, 90095, USA
| |
Collapse
|
10
|
Inoue R, Hosomi K, Park J, Sakaue H, Yumioka H, Kamitani H, Kinugasa Y, Harano K, Syauki AY, Doi M, Kageyama S, Yamamoto K, Mizuguchi K, Kunisawa J, Irie Y. Clinical Phenotypes Associated with the Gut Microbiome in Older Japanese People with Care Needs in a Nursing Home. Nutrients 2024; 16:3839. [PMID: 39599625 PMCID: PMC11597083 DOI: 10.3390/nu16223839] [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: 10/14/2024] [Revised: 10/28/2024] [Accepted: 11/01/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Frailty increases the risk of needing nursing care and significantly affects the life and functional prognosis of older individuals. Early detection and tailored interventions are crucial for maintaining and enhancing their life functions. Recognizing distinct clinical phenotypes is essential for devising appropriate interventions. This study aimed to explore diverse frailty phenotypes, focusing on poor nutrition in older Japanese individuals through observational research. METHODS Twenty-one nursing home residents underwent a comprehensive survey covering physical, blood, dietary, cardiac, cognitive, nutritional, nursing care, frailty, agitated behavior, and gut microbiome assessments (high-throughput 16S rRNA gene sequencing). Using clustering analysis with 239 survey items (excluding gut microbiome), participants were classified into subgroups based on clinical phenotypes, and group characteristics were compared through analysis. RESULTS Individuals with moderate or severe frailty and suspected dementia formed subgroups with distinct clinical phenotypes based on nutritional, defecation, and nursing care statuses. The gut microbiome significantly varied among these groups (p = 0.007), indicating its correlation with changes in clinical phenotype. Nutritional status differences suggested poor nutrition as a differentiating factor in the core clinical phenotype. CONCLUSIONS This study proposes that the gut microbiome differs based on the clinical phenotype of Japanese older individuals with frailty, and targeted interventions addressing the gut microbiome may contribute to preventing frailty in this population.
Collapse
Affiliation(s)
- Rikako Inoue
- Department of Nutritional Science, Faculty of Health and Welfare Science, Okayama Prefectural University, Soja City 719-1197, Okayama, Japan;
- Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Ibaraki City 567-0085, Osaka, Japan; (K.H.); (H.Y.); (J.K.)
| | - Koji Hosomi
- Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Ibaraki City 567-0085, Osaka, Japan; (K.H.); (H.Y.); (J.K.)
- Graduate School of Veterinary Science, Osaka Metropolitan University, Izumi-Sano City 598-0048, Osaka, Japan
| | - Jonguk Park
- Artificial Intelligence Center for Health and Biomedical Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Ibaraki City 567-0085, Osaka, Japan; (J.P.); (K.M.)
| | - Haruka Sakaue
- Graduate School of Health and Welfare Science, Okayama Prefectural University, Soja City 719-1197, Okayama, Japan; (H.S.); (A.Y.S.); (M.D.); (S.K.)
| | - Hitomi Yumioka
- Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Ibaraki City 567-0085, Osaka, Japan; (K.H.); (H.Y.); (J.K.)
- Faculty of Nutrition, Osaka Seikei College, Osaka City 533-0007, Osaka, Japan
| | - Hiroko Kamitani
- Department of Cardiovascular Medicine and Endocrinology and Metabolism, Faculty of Medicine, Tottori University, Yonago City 683-8503, Tottori, Japan; (H.K.); (Y.K.); (K.Y.)
| | - Yoshiharu Kinugasa
- Department of Cardiovascular Medicine and Endocrinology and Metabolism, Faculty of Medicine, Tottori University, Yonago City 683-8503, Tottori, Japan; (H.K.); (Y.K.); (K.Y.)
| | - Kaori Harano
- Department of Human Welfare, Faculty of Human Relations, Otsuma Women’s University, Tama City 206-8540, Tokyo, Japan;
| | - A. Yasmin Syauki
- Graduate School of Health and Welfare Science, Okayama Prefectural University, Soja City 719-1197, Okayama, Japan; (H.S.); (A.Y.S.); (M.D.); (S.K.)
- Department of Nutrition, Faculty of Medicine, Hasanuddin University, Tamalanrea 90245, Makassar, Indonesia
| | - Miki Doi
- Graduate School of Health and Welfare Science, Okayama Prefectural University, Soja City 719-1197, Okayama, Japan; (H.S.); (A.Y.S.); (M.D.); (S.K.)
| | - Suzumi Kageyama
- Graduate School of Health and Welfare Science, Okayama Prefectural University, Soja City 719-1197, Okayama, Japan; (H.S.); (A.Y.S.); (M.D.); (S.K.)
- Research Fellow of Japan Society for the Promotion of Science, Chiyoda City 102-0083, Tokyo, Japan
| | - Kazuhiro Yamamoto
- Department of Cardiovascular Medicine and Endocrinology and Metabolism, Faculty of Medicine, Tottori University, Yonago City 683-8503, Tottori, Japan; (H.K.); (Y.K.); (K.Y.)
| | - Kenji Mizuguchi
- Artificial Intelligence Center for Health and Biomedical Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Ibaraki City 567-0085, Osaka, Japan; (J.P.); (K.M.)
- Institute for Protein Research, Osaka University, Suita City 565-0871, Osaka, Japan
| | - Jun Kunisawa
- Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Ibaraki City 567-0085, Osaka, Japan; (K.H.); (H.Y.); (J.K.)
| | - Yasuyuki Irie
- Graduate School of Veterinary Science, Osaka Metropolitan University, Izumi-Sano City 598-0048, Osaka, Japan
| |
Collapse
|
11
|
Matsuura Y, Simons M, Hodo LN. Abdominal Pain in a 17-Year-Old Boy with an Eating Disorder. Clin Pediatr (Phila) 2024; 63:1620-1623. [PMID: 38380644 DOI: 10.1177/00099228241233867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/22/2024]
Affiliation(s)
- Yusuke Matsuura
- Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
| | - Melanie Simons
- Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
| | - Laura Nell Hodo
- Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
| |
Collapse
|
12
|
Jones S, Pheasant K, Dalton C, Green J, Moore C. Clinical Performance of the LiquidArray ® Gastrointestinal VER 1.0 Assay in Patients with Suspected Gastroenteritis. Diagnostics (Basel) 2024; 14:2377. [PMID: 39518345 PMCID: PMC11544872 DOI: 10.3390/diagnostics14212377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 10/11/2024] [Accepted: 10/20/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND/OBJECTIVES Rapid and accurate pathogen identification is essential for the proper management of patients with infectious gastroenteritis, as well as for a better control of disease outbreaks. This observational, non-interventional, single-site study evaluated the diagnostic accuracy of LiquidArray® Gastrointestinal VER 1.0, a multiplex PCR syndromic panel capable of detecting up to 26 clinically relevant enteropathogens. METHODS Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and likelihood ratio (LR) were evaluated using stool samples from 1512 patients with suspected gastroenteritis and were compared to seven competitor assays. RESULTS LiquidArray® Gastrointestinal VER 1.0 showed a very low invalid rate (0.5% at initial testing, down to 0% after repeat) and high sensitivity (>90% for most detected targets) and specificity (>99% for all detected targets). Accordingly, the PPV and NPV were high (>90% for most targets and >99% for all targets, respectively). The analytical performance of LiquidArray® Gastrointestinal VER 1.0 was also excellent as to co-amplification capability, cross-reactivity and assay precision. CONCLUSIONS This study demonstrates the excellent clinical performance of LiquidArray® Gastrointestinal VER 1.0 and its suitability for implementation in clinical routine for the rapid and accurate diagnosis of infectious gastroenteritis.
Collapse
Affiliation(s)
- Sophie Jones
- Bacteriology Department, Public Health Wales Microbiology Cardiff, University Hospital of Wales, Health Park, Cardiff CF14 4XW, UK;
| | - Kathleen Pheasant
- Wales Specialist Virology Centre, Public Health Wales Microbiology Cardiff, University Hospital of Wales, Health Park, Cardiff CF14 4XW, UK;
| | - Colette Dalton
- Bruker Microbiology and Infection Diagnostics, Bruker UK Limited, Nova Business Park, Glasgow G33 1AP, UK;
| | - Julie Green
- Bruker Microbiology and Infection Diagnostics, Bruker UK Limited, Nova Business Park, Glasgow G33 1AP, UK;
| | - Catherine Moore
- Wales Specialist Virology Centre, Public Health Wales Microbiology Cardiff, University Hospital of Wales, Health Park, Cardiff CF14 4XW, UK;
| |
Collapse
|
13
|
Hansen MM, Rågård N, Andreasen PW, Paaske SE, Dahlerup JF, Mikkelsen S, Erikstrup C, Baunwall SMD, Hvas CL. Encapsulated donor faeces for faecal microbiota transplantation: the Glyprotect protocol. Therap Adv Gastroenterol 2024; 17:17562848241289065. [PMID: 39421003 PMCID: PMC11483698 DOI: 10.1177/17562848241289065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 09/18/2024] [Indexed: 10/19/2024] Open
Abstract
Background Faecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection. Its use is backed by solid evidence, but application methods differ. Encapsulated FMT is a non-invasive, patient-friendly and scalable application method that may be preferred over colonoscopy or nasoduodenal tube application. Objectives We describe a detailed protocol, the Glyprotect protocol, for producing glycerol-based capsules to increase FMT accessibility. Design Using iterative quality improvement methods, we developed and validated the Glyprotect protocol as a reproducible protocol for cryopreserving minimally processed donor faeces in a standard hospital laboratory setting. Methods We describe detailed standard operating procedures for producing glycerol-based capsules, including all necessary materials and troubleshooting guidelines. Capsule integrity was tested at various temperatures and pH levels. Flow cytometry was used to measure microbiota counts and dose accuracy. Results The Glyprotect protocol has been used for more than 2500 capsule-based FMT treatments and complies with European tissue and cell standards. The protocol is optimised to preserve microbes and minimise modulation of the donated microbiota by removing debris and water, which also reduces the number of capsules needed per FMT treatment. The intestinal microbiota is preserved in glycerol for cryoprotection and to prevent capsule leakage. Each capsule contains 650 µL microbe-glycerol mass, estimated to contain an average of 2.5 × 108 non-specified bacteria. Conclusion The Glyprotect protocol enables hospitals and tissue establishments to set up capsule production in a standard laboratory, improving patients' access to FMT. The protocol facilitates the scalability of FMT services because capsule FMT is less time-consuming and less expensive than liquid-suspension FMT applied by colonoscopy or nasojejunal tube. Trial registration Not applicable.
Collapse
Affiliation(s)
- Mette Mejlby Hansen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Nina Rågård
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Pia Winther Andreasen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Sara Ellegaard Paaske
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Jens Frederik Dahlerup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Susan Mikkelsen
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
| | - Christian Erikstrup
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Christian Lodberg Hvas
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 35, Aarhus N, DK-8200, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| |
Collapse
|
14
|
Kim HS, Oh SJ, Kim BK, Kim JE, Kim BH, Park YK, Yang BG, Lee JY, Bae JW, Lee CK. Dysbiotic signatures and diagnostic potential of gut microbial markers for inflammatory bowel disease in Korean population. Sci Rep 2024; 14:23701. [PMID: 39390011 PMCID: PMC11467411 DOI: 10.1038/s41598-024-74002-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 09/23/2024] [Indexed: 10/12/2024] Open
Abstract
Fecal samples were collected from 640 individuals in Korea, including 523 patients with IBD (223 with Crohn's disease [CD] and 300 with ulcerative colitis [UC]) and 117 healthy controls. The samples were subjected to cross-sectional gut metagenomic analysis using 16 S rRNA sequencing and bioinformatics analysis. Patients with IBD, particularly those with CD, exhibited significantly lower alpha diversities than the healthy subjects. Differential abundance analysis revealed dysbiotic signatures, characterized by an expansion of the genus Escherichia-Shigella in patients with CD. Functional annotations showed that functional pathways related to bacterial pathogenesis and production of hydrogen sulfide (H2S) were strongly upregulated in patients with CD. A dysbiosis score, calculated based on functional characteristics, highly correlated with disease severity. Markers distinguishing between healthy subjects and patients with IBD showed accurate classification based on a small number of microbial taxa, which may be used to diagnose ambiguous cases. These findings confirm the taxonomic and functional dysbiosis of the gut microbiota in patients with IBD, especially those with CD. Taxa indicative of dysbiosis may have significant implications for future clinical research on the management and diagnosis of IBD.
Collapse
Affiliation(s)
- Hyun Sik Kim
- Department of Biology, Kyung Hee University, Seoul, Republic of Korea
| | - Shin Ju Oh
- Department of Gastroenterology, Center for Crohn's and Colitis, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Republic of Korea
| | - Byung Kwon Kim
- Research Institute, GI Biome Inc., Seongnam, Republic of Korea
| | - Ji Eun Kim
- Department of Gastroenterology, Center for Crohn's and Colitis, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Republic of Korea
| | - Bo-Hyung Kim
- Department of Clinical Pharmacology and Therapeutics, Kyung Hee University Hospital, Seoul, Republic of Korea
- East-West Medical Research Institute, Kyung Hee University, Seoul, Republic of Korea
| | - Young-Kyu Park
- Research Institute, GI Biome Inc., Seongnam, Republic of Korea
| | - Bo-Gie Yang
- Research Institute, GI Biome Inc., Seongnam, Republic of Korea
| | - Jae-Yun Lee
- Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea
| | - Jin-Woo Bae
- Department of Biology, Kyung Hee University, Seoul, Republic of Korea.
- Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea.
- Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea.
| | - Chang Kyun Lee
- Department of Gastroenterology, Center for Crohn's and Colitis, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Republic of Korea.
| |
Collapse
|
15
|
Matsuura N, Kanayama M, Watanabe Y, Yamada H, Lili L, Torii A. Effect of Personalized Prebiotic and Probiotic Supplements on the Symptoms of Irritable Bowel Syndrome: An Open-Label, Single-Arm, Multicenter Clinical Trial. Nutrients 2024; 16:3333. [PMID: 39408300 PMCID: PMC11478705 DOI: 10.3390/nu16193333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 09/26/2024] [Accepted: 09/29/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND/OBJECTIVES Prebiotics and probiotics have been reported to improve symptoms of irritable bowel syndrome (IBS). Nevertheless, the effects of prebiotics/probiotics can vary depending on the IBS subtypes. The purpose of this study was to investigate the effects of personalized prebiotic and probiotic supplements based on intestinal microbiota and IBS subtypes in patients. METHODS Patients with diarrhea-type IBS (IBS-D), constipation-type IBS (IBS-C), and mixed-type IBS (IBS-M) were enrolled (n = 40 per group; total: n = 120). Personalized prebiotic and probiotic supplements were determined according to the IBS subtypes and intestinal microbiota. The patients received supplements for 4 weeks. The primary outcome was the change in the IBS-severity scoring system from baseline to week 4. RESULTS The IBS-severity scoring system significantly decreased in all patients (-38.0 [95% confidence interval (CI): -53.6, -22.4]; p < 0.001), in patients with IBS-D (-44.5 [95% CI: -70.6, -18.5]; p = 0.004) and IBS-C (-51.2 [95% CI: -79.4, -22.9]; p = 0.002), but not in those with IBS-M (-20.0 [95% CI: -48.0, 8.1]; p = 0.47). In this study, no serious adverse events were observed that had a causal relationship with the intervention. CONCLUSIONS In conclusion, personalized prebiotic and probiotic supplements selected according to individual intestinal microbiota and IBS subtype may alleviate the severity of IBS symptoms, particularly in patients with IBS-C and IBS-D.
Collapse
Affiliation(s)
- Nozomi Matsuura
- Institute of Health Science, Health Science Business Division, Kirin Holdings Company, Limited, Fujisawa, Kanagawa 251-8555, Japan; (N.M.); (Y.W.)
| | - Masaya Kanayama
- Institute of Health Science, Health Science Business Division, Kirin Holdings Company, Limited, Fujisawa, Kanagawa 251-8555, Japan; (N.M.); (Y.W.)
| | - Yuta Watanabe
- Institute of Health Science, Health Science Business Division, Kirin Holdings Company, Limited, Fujisawa, Kanagawa 251-8555, Japan; (N.M.); (Y.W.)
| | - Hirokazu Yamada
- Soiken Inc., Chiyoda, Tokyo 101-0052, Japan
- EviPRO Co., Ltd., Chiyoda, Tokyo 101-0032, Japan
| | - Loukia Lili
- Thorne HealthTech, Inc., New York, NY 10019, USA
| | - Akira Torii
- Torii Medical Clinic, Setagaya, Tokyo 157-0066, Japan
| |
Collapse
|
16
|
Tsujibe S, Gawad A, Shigehisa A, Matsuda K, Fujimoto J, Takahashi T. Evaluating the Effect of Lacticaseibacillus paracasei Strain Shirota on the Physical Consistency of Stool in Healthy Participants with Hard or Lumpy Stools: A Double-Blind, Randomized, Placebo-Controlled Study. Nutrients 2024; 16:2469. [PMID: 39125350 PMCID: PMC11313875 DOI: 10.3390/nu16152469] [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: 06/28/2024] [Revised: 07/22/2024] [Accepted: 07/25/2024] [Indexed: 08/12/2024] Open
Abstract
We have earlier established a direct measurement method for assessing stool physical consistency using a texture analyzer (TAXT). The present study aimed to evaluate the stool softening effect of Lacticaseibacillus paracasei strain Shirota (LcS) using TAXT in a double-blind, randomized, placebo-controlled study. Sixty-four healthy participants with a Bristol stool form scale (BSFS) 1/2 ≥ 50% during screening consumed fermented milk containing LcS or a placebo beverage daily for 8 weeks. Stool consistency and water content were determined using TAXT and a lyophilizer, respectively. Participants evaluated their defecation using the BSFS. Stool consistency evaluated by a texture analyzer (TAXT) in the LcS group tended to be softer than that in the placebo group (p = 0.052). Subgroup analyses (TAXT value at baseline ≥ 4.5) showed that stool consistency was significantly softer in the LcS group (p = 0.014). Stool water content was also significantly higher in the LcS group than in the placebo group, but the proportion of normal stools was not statistically significant. We were unable to find evidence for the softening effect of LcS under the present study's conditions. However, its efficacy may be confirmed by targeting participants with physically hard stools and TAXT values ≥ 4.5.
Collapse
Affiliation(s)
- Satoshi Tsujibe
- Yakult Central Institute, 5-11 Izumi, Kunitachi-shi 186-8650, Tokyo, Japan; (A.S.); (K.M.); (J.F.)
| | - Agata Gawad
- Yakult Honsha European Research Center for Microbiology VOF, Technologiepark 94, 9052 Ghent, East Flanders, Belgium; (A.G.); (T.T.)
| | - Akira Shigehisa
- Yakult Central Institute, 5-11 Izumi, Kunitachi-shi 186-8650, Tokyo, Japan; (A.S.); (K.M.); (J.F.)
| | - Kazunori Matsuda
- Yakult Central Institute, 5-11 Izumi, Kunitachi-shi 186-8650, Tokyo, Japan; (A.S.); (K.M.); (J.F.)
| | - Junji Fujimoto
- Yakult Central Institute, 5-11 Izumi, Kunitachi-shi 186-8650, Tokyo, Japan; (A.S.); (K.M.); (J.F.)
| | - Takuya Takahashi
- Yakult Honsha European Research Center for Microbiology VOF, Technologiepark 94, 9052 Ghent, East Flanders, Belgium; (A.G.); (T.T.)
| |
Collapse
|
17
|
Tanihiro R, Yuki M, Sakano K, Sasai M, Sawada D, Ebihara S, Hirota T. Effects of Heat-Treated Lactobacillus helveticus CP790-Fermented Milk on Gastrointestinal Health in Healthy Adults: A Randomized Double-Blind Placebo-Controlled Trial. Nutrients 2024; 16:2191. [PMID: 39064634 PMCID: PMC11280423 DOI: 10.3390/nu16142191] [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: 06/24/2024] [Revised: 07/04/2024] [Accepted: 07/05/2024] [Indexed: 07/28/2024] Open
Abstract
Probiotic-fermented milk is commonly used to maintain intestinal health. However, the effects of heat-treated fermented milk, which does not contain live microorganisms, on intestinal function are not yet fully understood. This study aimed to investigate whether heat-treated Lactobacillus helveticus CP790-fermented milk affects fecal microbiota and gut health as a "postbiotic". A randomized, double-blind, placebo-controlled trial was conducted in healthy Japanese individuals aged 20-59 years with a tendency toward constipation. Participants consumed 100 mL of either the test beverage (n = 60) or placebo beverage (n = 60) for four weeks. The test beverages were prepared with heat-treated CP790-fermented milk, while the placebo beverages were prepared with nonfermented milk flavored with lactic acid. Fecal samples were analyzed using 16S rRNA gene sequencing. Constipation symptoms were assessed using defecation logs and the Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire. Mood state was also assessed using the Profile of Mood States 2 (POMS2) questionnaire to explore its potential as a "psychobiotic". Desulfobacterota were significantly decreased by CP790-fermented milk intake. PICRUSt2 analysis predicted a decrease in the proportion of genes involved in the sulfate reduction pathway following the consumption of CP790-fermented milk. The CP790-fermented milk intervention significantly improved stool consistency and straining during defecation. These improvements were correlated with a decrease in Desulfobacterota. After the intervention, overall mood, expressed as total mood disturbance, and depression-dejection were significantly better in the CP790 group than in the placebo group. These results suggest that the intake of CP790-fermented milk could be effective in modulating gut microbiota and improving constipation symptoms and mood states.
Collapse
Affiliation(s)
- Reiko Tanihiro
- Core Technology Laboratories, Asahi Quality and Innovations, Ltd., Moriya 302-0106, Japan; (M.Y.); (K.S.); (M.S.); (D.S.); (T.H.)
| | - Masahiro Yuki
- Core Technology Laboratories, Asahi Quality and Innovations, Ltd., Moriya 302-0106, Japan; (M.Y.); (K.S.); (M.S.); (D.S.); (T.H.)
| | - Katsuhisa Sakano
- Core Technology Laboratories, Asahi Quality and Innovations, Ltd., Moriya 302-0106, Japan; (M.Y.); (K.S.); (M.S.); (D.S.); (T.H.)
| | - Masaki Sasai
- Core Technology Laboratories, Asahi Quality and Innovations, Ltd., Moriya 302-0106, Japan; (M.Y.); (K.S.); (M.S.); (D.S.); (T.H.)
| | - Daisuke Sawada
- Core Technology Laboratories, Asahi Quality and Innovations, Ltd., Moriya 302-0106, Japan; (M.Y.); (K.S.); (M.S.); (D.S.); (T.H.)
| | | | - Tatsuhiko Hirota
- Core Technology Laboratories, Asahi Quality and Innovations, Ltd., Moriya 302-0106, Japan; (M.Y.); (K.S.); (M.S.); (D.S.); (T.H.)
| |
Collapse
|
18
|
Clevers E, Launders D, Helme D, Nybacka S, Störsrud S, Corsetti M, Van Oudenhove L, Simrén M, Tack J. Coffee, Alcohol, and Artificial Sweeteners Have Temporal Associations with Gastrointestinal Symptoms. Dig Dis Sci 2024; 69:2522-2529. [PMID: 38662159 DOI: 10.1007/s10620-024-08457-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Accepted: 04/17/2024] [Indexed: 04/26/2024]
Abstract
BACKGROUND Various dietary strategies for managing irritable bowel syndrome (IBS) target mechanisms such as brain-gut interactions, osmotic actions, microbial gas production, and local immune activity. These pathophysiological mechanisms are diverse, making it unclear which foods trigger IBS symptoms for a substantial proportion of patients. AIM To identify associations between foods and gastrointestinal symptoms. METHODS From the mySymptoms smartphone app, we collected anonymized diaries of food intake and symptoms (abdominal pain, diarrhea, bloating, and gas). We selected diaries that were at least 3 weeks long. The diaries were analyzed for food-symptom associations using a proprietary algorithm. As the participants were anonymous, we conducted an app-wide user survey to identify IBS diagnoses according to Rome IV criteria. RESULTS A total of 9,710 food symptom diaries that met the quality criteria were collected. Of the survey respondents, 70% had IBS according to Rome IV criteria. Generally, strong associations existed for caffeinated coffee (diarrhea, 1-2 h postprandial), alcoholic beverages (multiple symptoms, 4-72 h postprandial), and artificial sweeteners (multiple symptoms, 24-72 h postprandial). Histamine-rich food intake was associated with abdominal pain and diarrhea. Some associations are in line with existing literature, whilst the absence of an enriched FODMAP-symptom association contrasts with current knowledge. CONCLUSIONS Coffee, alcohol, and artificial sweeteners were associated with GI symptoms in this large IBS-predominant sample. Symptom onset is often within 2 h postprandial, but some foods were associated with a delayed response, possibly an important consideration in implementing dietary recommendations. Clinical trials must test the causality of the demonstrated food-symptom associations.
Collapse
Affiliation(s)
- Egbert Clevers
- SkyGazer Labs Ltd, Cambridge, UK.
- The Data Strategist, Duiven, the Netherlands.
| | | | | | - Sanna Nybacka
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Stine Störsrud
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Maura Corsetti
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Lukas Van Oudenhove
- Translational Research Centre for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| | - Magnus Simrén
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Center for Functional GI and Motility Disorders, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA
| | - Jan Tack
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Translational Research Centre for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
| |
Collapse
|
19
|
Dönmez Mİ, Selvi I, Oktar T, Ziylan O. Urotherapy and biofeedback resistant dysfunctional voiding: How to deal with? Low Urin Tract Symptoms 2024; 16:e12528. [PMID: 38923750 DOI: 10.1111/luts.12528] [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: 02/15/2024] [Revised: 06/07/2024] [Accepted: 06/05/2024] [Indexed: 06/28/2024]
Abstract
OBJECTIVES To analyze the management strategies in the children who had treatment-resistant dysfunctional voiding (DV). METHODS Among 75 children with DV who underwent pelvic floor biofeedback therapy (BF) between 2013 and 2020, 16 patients (14 girls, 87.5%) with a mean age of 9.81 ± 2.53 years that showed incomplete clinical response following urotherapy and initial BF sessions were retrospectively reviewed. The demographic and clinical characteristics, DVSS, and uroflowmetry parameters were recorded before and after the initial BF sessions. Subsequent treatments after initial BF and clinical responses of patients were noted. RESULTS Clinical success was observed in one patient by addition of an anticholinergic and in three patients with combination of salvage BF sessions and anticholinergics, whom had predominant overactive bladder (OAB) symptoms. The success rate of TENS alone and in combination with other treatment modalities was 88.8% (8/9 patients). In addition, salvage BF sessions (range 2 to 3) enabled clinical success in five (50%) of 10 cases as a combination with anticholinergics or TENS. In case of incomplete emptying without OAB, adequate clinical response to Botulinum-A was observed during an average follow-up of 29 months in two boys who did not respond to alpha-blockers, even though one required repeat injection after 10 months. The total clinical success rate was 87.5% (14/16 patients) after a median follow-up of 24 months. VV-EBC and Qmax increased by a mean of 30.89% and 7.13 mL/min, respectively, whereas DVSS decreased by a mean of 8.88 points and PVR-EBC decreased by a median of 19.04%. CONCLUSIONS Our findings showed that clinical success in resistant DV was achieved by various combination treatments in the majority of children. However, a small group may still have persistent, bothersome symptoms despite multiple treatment modalities.
Collapse
Affiliation(s)
- M İrfan Dönmez
- İstanbul Faculty of Medicine, Department of Urology, Division of Pediatric Urology, İstanbul University, Istanbul, Turkey
| | - Ismail Selvi
- İstanbul Faculty of Medicine, Department of Urology, Division of Pediatric Urology, İstanbul University, Istanbul, Turkey
| | - Tayfun Oktar
- İstanbul Faculty of Medicine, Department of Urology, Division of Pediatric Urology, İstanbul University, Istanbul, Turkey
- School of Medicine, Department of Urology, Koç University, Istanbul, Turkey
| | - Orhan Ziylan
- İstanbul Faculty of Medicine, Department of Urology, Division of Pediatric Urology, İstanbul University, Istanbul, Turkey
| |
Collapse
|
20
|
Watanabe N, Itano A, Ando M, Kawahara M. Effect of reduced daily magnesium oxide doses on laxative effect: a single-center retrospective study. J Rural Med 2024; 19:192-195. [PMID: 38975042 PMCID: PMC11222616 DOI: 10.2185/jrm.2023-038] [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: 10/13/2023] [Accepted: 02/19/2024] [Indexed: 07/09/2024] Open
Abstract
Objective: To investigate the laxative effect of reducing the number of daily doses of magnesium oxide (MgO), while maintaining the total daily dose of MgO in patients with good bowel movements. Patients and Methods: The retrospective analysis involved 11 patients with regular bowel movements who were prescribed MgO for constipation upon admission to a nursing care facility accompanied by home visits by a pharmacist. This investigation was conducted before and after reducing the number of daily doses from three to two, or from two to one, over a two-week period. Results: The number of bowel movements was 7.6 ± 3.4 and 6.6 ± 4.0 times for two weeks before and after the change in dosage frequency, respectively. The difference was not statistically significant (P=0.09). The Bristol Stool Form Scale was 3.9 ± 0.9 and 4.0 ± 0.9 two weeks before and after the change, respectively, which was not significant (P=0.93). Two weeks after the change, the MgO regimen remained unchanged and no on-demand laxatives were administered. Conclusions: The results suggest that reducing the number of daily doses of MgO does not affect its laxative action.
Collapse
Affiliation(s)
- Norio Watanabe
- Department of Pharmaceutical Sciences, School of Pharmacy, Aichi Gakuin University, Japan
| | | | - Motozumi Ando
- Department of Pharmaceutical Sciences, School of Pharmacy, Aichi Gakuin University, Japan
| | - Masami Kawahara
- Department of Pharmaceutical Sciences, School of Pharmacy, Aichi Gakuin University, Japan
| |
Collapse
|
21
|
Suzuki K, Onodera H, Sugiyama R, Okubo S, Kimura N, Kaku S, Seki R, Fujita S, Nomura K, Takagiwa T, Katafuchi I, Nakamura H, Kanamaru T, Oda M, Kimura S, Sonoda S, Kakita H, Otsuka T, Kimura K. The randomized study of enteral nutrition with rapid versus conventional administration in acute stroke patients; the protocol of rapid EN trial. Front Neurol 2024; 15:1393345. [PMID: 38887387 PMCID: PMC11181348 DOI: 10.3389/fneur.2024.1393345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 05/20/2024] [Indexed: 06/20/2024] Open
Abstract
Rationale Enteral nutrition is beneficial for stroke patients with oral intake difficulties. However, it is time consuming and may interfere with routine medical care. Therefore, there is a clinical benefit if enteral nutrition can be safely administered in a short time. Although our retrospective study showed the safety of rapid administration, it remains unclear whether rapid administration of enteral nutrition is as safe as conventional administration. Aim The randomized study of Enteral Nutrition with Rapid versus conventional administration in acute stroke patients (Rapid EN trial) aims to clarify the safety of rapid feeding of enteral nutrition compared with conventional feeding. Methods and design This is an investigator-initiated, multicenter, prospective, randomized, open-label, blinded end-point clinical trial. Eligible criteria include acute stroke patients who have difficulty with oral intake defined as severe altered consciousness (Japan Coma Scale 10-300) or modified water swallowing test <4. The target enrollment is 700 patients, with 350 patients receiving rapid enteral nutrition at a rate of 100 mL in 5 min (Rapid EN group) and 350 patients receiving conventional enteral nutrition at a rate of 100 mL in 30 min (Conventional EN group). Study outcome The primary outcome is the incidence of one or more complications of vomiting or diarrhea or pneumonia within 7 days would be non-inferior in the rapid EN group compared to the conventional EN group. Secondary outcomes were total time spent on enteral nutrition within 7 days from enteral nutrition, the incidence of vomiting, diarrhea and pneumonia within 3 or 7 days, and the rate of favorable clinical outcome. Discussion Since no previous reports have focused on the speed of administration, we felt it was necessary to prove the safety of rapid administration. If this study shows positive results, it will not only benefit patients, but also reduce the burden of medical care. We believe this study is novel and will be useful in clinical practice. Clinical trial registration https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000046610 Identifier UMIN000046610.
Collapse
Affiliation(s)
- Kentaro Suzuki
- Department of Neurology, Nippon Medical School, Tokyo, Japan
| | - Hidetaka Onodera
- Department of Neurosurgery, St. Marianna University School Toyoko Hospital, Kawasaki, Kanagawa, Japan
| | - Rie Sugiyama
- Emergency and Critical Care Center, Nippon Medical School, Tokyo, Japan
| | - Seiji Okubo
- Department of Cerebrovascular Medicine, NTT Medical Center Tokyo, Tokyo, Japan
| | - Naoto Kimura
- Department of Neurosurgery, Iwate Prefectural Central Hospital, Morioka, Iwate, Japan
| | - Shogo Kaku
- Department of Neurosurgery, Neurosurgical East Yokohama Hospital, Yokohama, Kanagawa, Japan
| | - Rieko Seki
- Department of Neurosurgery, Shimizu Hospital, Kyoto, Japan
| | - Satoshi Fujita
- Department of Neurosurgery, Toho University Ohashi Medical Center, Tokyo, Japan
| | - Koichi Nomura
- Department of Neurology, Shioda Hospital, Chiba, Japan
| | | | | | - Homare Nakamura
- Department of Neurosurgery, St. Marianna University Yokohama Seibu Hospital, Yokohama, Kanagawa, Japan
| | - Takuya Kanamaru
- Department of Cerebrovascular Medicine, NTT Medical Center Tokyo, Tokyo, Japan
| | - Momoyo Oda
- Department of Neurology, Iwate Prefectural Central Hospital, Morioka, Iwate, Japan
| | - Shohei Kimura
- Department of Neurosurgery, Neurosurgical East Yokohama Hospital, Yokohama, Kanagawa, Japan
| | - Shota Sonoda
- Department of Neurosurgery, Neurosurgical East Yokohama Hospital, Yokohama, Kanagawa, Japan
| | - Hiroto Kakita
- Department of Neurosurgery, Shimizu Hospital, Kyoto, Japan
| | - Toshiaki Otsuka
- Department of Public Health, Nippon Medical School, Tokyo, Japan
| | - Kazumi Kimura
- Department of Neurology, Nippon Medical School, Tokyo, Japan
| |
Collapse
|
22
|
Guo H, Chen Y, Dong W, Lu S, Du Y, Duan L. Fecal Coprococcus, hidden behind abdominal symptoms in patients with small intestinal bacterial overgrowth. J Transl Med 2024; 22:496. [PMID: 38796441 PMCID: PMC11128122 DOI: 10.1186/s12967-024-05316-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Accepted: 05/20/2024] [Indexed: 05/28/2024] Open
Abstract
BACKGROUND Small intestinal bacterial overgrowth (SIBO) is the presence of an abnormally excessive amount of bacterial colonization in the small bowel. Hydrogen and methane breath test has been widely applied as a non-invasive method for SIBO. However, the positive breath test representative of bacterial overgrowth could also be detected in asymptomatic individuals. METHODS To explore the relationship between clinical symptoms and gut dysbiosis, and find potential fecal biomarkers for SIBO, we compared the microbial profiles between SIBO subjects with positive breath test but without abdominal symptoms (PBT) and healthy controls (HC) using 16S rRNA amplicon sequencing. RESULTS Fecal samples were collected from 63 SIBO who complained of diarrhea, distension, constipation, or abdominal pain, 36 PBT, and 55 HC. For alpha diversity, the Shannon index of community diversity on the genus level showed a tendency for a slight increase in SIBO, while the Shannon index on the predicted function was significantly decreased in SIBO. On the genus level, significantly decreased Bacteroides, increased Coprococcus_2, and unique Butyrivibrio were observed in SIBO. There was a significant positive correlation between saccharolytic Coprococcus_2 and the severity of abdominal symptoms. Differently, the unique Veillonella in the PBT group was related to amino acid fermentation. Interestingly, the co-occurrence network density of PBT was larger than SIBO, which indicates a complicated interaction of genera. Coprococcus_2 showed one of the largest betweenness centrality in both SIBO and PBT microbiota networks. Pathway analysis based on the Kyoto Encyclopedia of Genes and Genome (KEGG) database reflected that one carbon pool by folate and multiple amino acid metabolism were significantly down in SIBO. CONCLUSIONS This study provides valuable insights into the fecal microbiota composition and predicted metabolic functional changes in patients with SIBO. Butyrivibrio and Coprococcus_2, both renowned for their role in carbohydrate fermenters and gas production, contributed significantly to the symptoms of the patients. Coprococcus's abundance hints at its use as a SIBO marker. Asymptomatic PBT individuals show a different microbiome, rich in Veillonella. PBT's complex microbial interactions might stabilize the intestinal ecosystem, but further study is needed due to the core microbiota similarities with SIBO. Predicted folate and amino acid metabolism reductions in SIBO merit additional validation.
Collapse
Affiliation(s)
- Huaizhu Guo
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Yuzhu Chen
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Wenxin Dong
- Department of Pediatrics, Peking University Third Hospital, Beijing, China
| | - Siqi Lu
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Yanlin Du
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Liping Duan
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
- International Institute of Population Health, Peking University Health Science Center, Beijing, China.
| |
Collapse
|
23
|
Jansson-Rehnberg AS, Drewes AM, Sponheim J, Borgfelt C, Münch A, Graf W, Simrén M, Lindberg G, Hellström PM. Diarrhoea of unknown cause: medical treatment in a stepwise manner Management of Idiopathic Diarrhoea Based on Experience of Step-Up Medical Treatment. Scand J Gastroenterol 2024; 59:543-546. [PMID: 38343268 DOI: 10.1080/00365521.2024.2313061] [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: 10/25/2023] [Revised: 12/05/2023] [Accepted: 01/25/2024] [Indexed: 04/26/2024]
Abstract
The basic principle for the treatment of idiopathic diarrhoea (functional diarrhoea K59.1) is to delay transit through the gut in order to promote the absorption of electrolytes and water. Under mild conditions, bulking agents may suffice. With increasing severity, antidiarrhoeal pharmaceuticals may be added in a stepwise manner. In diarrhoea of unknown aetiology, peripherally-acting opioid receptor agonists, such as loperamide, are first-line treatment and forms the pharmaceutical basis of antidiarrheal treatment. As second-line treatment opium drops have an approved indication for severe diarrhoea when other treatment options fail. Beyond this, various treatment options are built on experience with more advanced treatments using clonidine, octreotide, as well as GLP-1 and GLP-2 analogs which require specialist knowledge the field.
Collapse
Affiliation(s)
| | - Asbjørn Mohr Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Jon Sponheim
- Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Christer Borgfelt
- Department of obstetrics and gynaecology, Skåne University Hospital, Lund, Sweden
| | - Andreas Münch
- Department of Gastrointestinal Medicine, University Hospital, Linköping, Sweden
| | - Wilhelm Graf
- Department of Surgical Sciences, University of Uppsala, Sweden
| | - Magnus Simrén
- Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden
| | - Greger Lindberg
- Department of Medicine, Karolinska University Hospital, Huddinge, Sweden
| | - Per M Hellström
- Department of Medical Sciences, University of Uppsala, Sweden
| |
Collapse
|
24
|
Wong S, Hirani SP, Forbes A, Kumar N, Hariharan R, O'Driscoll J, Sekhar R, Jamous A. Lactobacillus casei Shirota probiotic drinks reduce antibiotic associated diarrhoea in patients with spinal cord injuries who regularly consume proton pump inhibitors: a subgroup analysis of the ECLISP multicentre RCT. Spinal Cord 2024; 62:255-263. [PMID: 38519563 PMCID: PMC11176055 DOI: 10.1038/s41393-024-00983-w] [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: 06/13/2023] [Revised: 03/08/2024] [Accepted: 03/13/2024] [Indexed: 03/25/2024]
Abstract
STUDY DESIGN This was a sub-group analysis of a multicentre, randomised, placebo-controlled, double-blind trial (ECLISP trial) OBJECTIVES: To assess the efficacy of a probiotic containing at least 6.5 × 109 live Lactobacillus casei Shirota (LcS) in preventing antibiotic associated diarrhoea (AAD) in patients with spinal cord injury (SCI) who consumed proton pump inhibitor (PPI) regularly. LcS or placebo was given once daily for the duration of an antibiotic course and continued for 7 days thereafter. The trial was registered with ISRCTN:13119162. SETTING Three SCI centres (National Spinal Injuries Centre, Midland Centre for Spinal Injuries and Princess Royal Spinal Cord Injuries Centre) in the United Kingdom METHODS: Between November 2014, and November 2019, 95 eligible consenting SCI patients (median age: 57; IQ range: 43-69) were randomly allocated to receive LcS (n = 50) or placebo (n = 45). The primary outcome is the occurrence of AAD up to 30 days after finishing LcS/placebo. RESULTS The LcS group had a significantly lower incidence of AAD at 30 days after finishing the antibiotic course (28.0 v 53.3%, RR: 95% CI: 0.53, 0.31-0.89; z = 2.5, p = 0.01). Multivariate logistic regression analysis identified that LcS can reduce the risk of AAD at 30 days (OR: 0.36, 95% CI 0.13, 0.99, p < 0.05). No intervention-related adverse events were reported during the study. CONCLUSIONS LcS has the potential to prevent AAD in what could be considered a defined vulnerable group of SCI patients on regular PPI. A confirmatory, randomised, placebo-controlled study is needed to confirm this apparent therapeutic success to translate it into appropriate clinical outcomes. SPONSORSHIP Yakult Honsha Co., Ltd.
Collapse
Affiliation(s)
- Samford Wong
- National Spinal Injuries Centre, Stoke Mandeville Hospital, Aylesbury, UK.
- School of Health & Psychological Sciences, City, University of London, London, UK.
- Royal Buckinghamshire Hospital, Aylesbury, UK.
| | - Shashivadan P Hirani
- School of Health & Psychological Sciences, City, University of London, London, UK
| | - Alastair Forbes
- University of Tartu, Estonia, and Norwich Medical School, University of East Anglia, Norwich, UK
| | - Naveen Kumar
- Midland Centre for Spinal Injury, Robert Jones and Agnes Hunt Orthopaedic Hospital, Gobowen, UK
| | - Ramaswamy Hariharan
- The Princess Royal Spinal Injuries Centre, Northern General Hospital, Sheffield, UK
| | - Jean O'Driscoll
- Department of Microbiology, Stoke Mandeville Hospital, Aylesbury, UK
| | - Ravi Sekhar
- Department of Gastroenterology, Stoke Mandeville Hospital, Aylesbury, UK
| | | |
Collapse
|
25
|
de Graaf MC, Timmers E, Bonekamp B, van Rooy G, Witteman BJ, Shewry PR, Lovegrove A, America AH, Gilissen LJ, Keszthelyi D, Brouns FJ, Jonkers DMAE. Two randomized crossover multicenter studies investigating gastrointestinal symptoms after bread consumption in individuals with noncoeliac wheat sensitivity: do wheat species and fermentation type matter? Am J Clin Nutr 2024; 119:896-907. [PMID: 38373694 DOI: 10.1016/j.ajcnut.2024.02.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 02/14/2024] [Accepted: 02/16/2024] [Indexed: 02/21/2024] Open
Abstract
BACKGROUND Many individuals reduce their bread intake because they believe wheat causes their gastrointestinal (GI) symptoms. Different wheat species and processing methods may affect these responses. OBJECTIVES We investigated the effects of 6 different bread types (prepared from 3 wheat species and 2 fermentation conditions) on GI symptoms in individuals with self-reported noncoeliac wheat sensitivity (NCWS). METHODS Two parallel, randomized, double-blind, crossover, multicenter studies were conducted. NCWS individuals, in whom coeliac disease and wheat allergy were ruled out, received 5 slices of yeast fermented (YF) (study A, n = 20) or sourdough fermented (SF) (study B, n = 20) bread made of bread wheat, spelt, or emmer in a randomized order on 3 separate test days. Each test day was preceded by a run-in period of 3 d of a symptom-free diet and separated by a wash-out period of ≥7 d. GI symptoms were evaluated by change in symptom score (test day minus average of the 3-d run-in period) on a 0-100 mm visual analogue scale (ΔVAS), comparing medians using the Friedman test. Responders were defined as an increase in ΔVAS of ≥15 mm for overall GI symptoms, abdominal discomfort, abdominal pain, bloating, and/or flatulence. RESULTS GI symptoms did not differ significantly between breads of different grains [YF bread wheat median ΔVAS 10.4 mm (IQR 0.0-17.8 mm), spelt 4.9 mm (-7.6 to 9.4 mm), emmer 11.0 mm (0.0-21.3 mm), P = 0.267; SF bread wheat 10.5 mm (-3.1 to 31.5 mm), spelt 11.3 mm (0.0-15.3 mm), emmer 4.0 mm (-2.9 to 9.3 mm), P = 0.144]. The number of responders was also comparable for both YF (6 to wheat, 5 to spelt, and 7 to emmer, P = 0.761) and SF breads (9 to wheat, 7 to spelt, and 8 to emmer, P = 0.761). CONCLUSIONS The majority of NCWS individuals experienced some GI symptoms for ≥1 of the breads, but on a group level, no differences were found between different grains for either YF or SF breads. CLINICAL TRIAL REGISTRY clinicaltrials.gov, NCT04084470 (https://classic. CLINICALTRIALS gov/ct2/show/NCT04084470).
Collapse
Affiliation(s)
- Marlijne Cg de Graaf
- Department of Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, The Netherlands
| | - Emma Timmers
- Department of Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, The Netherlands
| | - Bo Bonekamp
- Department of Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, The Netherlands
| | - Gonny van Rooy
- Department of Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, The Netherlands
| | - Ben Jm Witteman
- Division Gastroenterology-Hepatology, Gelderse Vallei Hospital, Ede, The Netherlands; Division of Human Nutrition, Wageningen University & Research, Wageningen, The Netherlands
| | | | | | - Antoine Hp America
- Business Unit Bioscience, Plant Sciences Group, Wageningen University & Research, Wageningen, The Netherlands
| | - Luud Jwj Gilissen
- Plant Breeding, Wageningen University & Research, Wageningen, The Netherlands
| | - Daniel Keszthelyi
- Department of Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, The Netherlands
| | - Fred Jph Brouns
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, The Netherlands; Department of Human Biology, Maastricht University, Maastricht, The Netherlands
| | - Daisy M A E Jonkers
- Department of Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, The Netherlands.
| |
Collapse
|
26
|
Ou Y, Belzer C, Smidt H, de Weerth C. Development of the gut microbiota in the first 14 years of life and its relations to internalizing and externalizing difficulties and social anxiety during puberty. Eur Child Adolesc Psychiatry 2024; 33:847-860. [PMID: 37071196 PMCID: PMC10894087 DOI: 10.1007/s00787-023-02205-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 04/03/2023] [Indexed: 04/19/2023]
Abstract
Relations between the gut microbiota and host mental health have been suggested by a growing number of case-control and cross-sectional studies, while supporting evidence is limited in large community samples followed during an extended period. Therefore, the current preregistered study ( https://osf.io/8ymav , September 7, 2022) described child gut microbiota development in the first 14 years of life and explored its relations to internalizing and externalizing difficulties and social anxiety in puberty, a period of high relevance for the development of mental health problems. Fecal microbiota composition was analysed by 16S ribosomal RNA gene amplicon sequencing in a total of 1003 samples from 193 children. Through a clustering method, four distinct microbial clusters were newly identified in puberty. Most children within three of these clusters remained in the same clusters from the age of 12 to 14 years, suggesting stability in microbial development and transition during this period. These three clusters were compositionally similar to enterotypes (i.e., a robust classification of the gut microbiota based on its composition across different populations) enriched in Bacteroides, Prevotella, and Ruminococcus, respectively. Two Prevotella 9-predominated clusters, including one reported by us earlier in middle childhood and the other one in puberty, were associated with more externalizing behavior at age 14. One Faecalibacterium-depleted pubertal cluster was related to more social anxiety at age 14. This finding was confirmed by a negative cross-sectional relation between Faecalibacterium and social anxiety in the 14-year-olds. The findings of this study continue to map gut microbiota development in a relatively large community sample followed from birth onwards, importantly extending our knowledge to puberty. Results indicate that Prevotella 9 and Faecalibacterium may be relevant microbial taxa in relation to externalizing behavior and social anxiety, respectively. These correlational findings need validations from other similar cohort studies, as well as well-designed mechanistic pre-clinical investigations before inferring cause and effect.
Collapse
Affiliation(s)
- Yangwenshan Ou
- Laboratory of Microbiology, Wageningen University and Research, P.O. Box 8033, 6700 EH, Wageningen, The Netherlands.
- Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Radboud University Medical Center, P.O. Box 9010, 6500 GL, Nijmegen, The Netherlands.
| | - Clara Belzer
- Laboratory of Microbiology, Wageningen University and Research, P.O. Box 8033, 6700 EH, Wageningen, The Netherlands
| | - Hauke Smidt
- Laboratory of Microbiology, Wageningen University and Research, P.O. Box 8033, 6700 EH, Wageningen, The Netherlands
| | - Carolina de Weerth
- Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Radboud University Medical Center, P.O. Box 9010, 6500 GL, Nijmegen, The Netherlands
| |
Collapse
|
27
|
Zhu JY, Liu MY, Sun C. Assessment of the triglyceride glucose index in adult patients with chronic diarrhea and constipation. World J Clin Cases 2024; 12:1094-1103. [PMID: 38464922 PMCID: PMC10921306 DOI: 10.12998/wjcc.v12.i6.1094] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 01/03/2024] [Accepted: 01/19/2024] [Indexed: 02/20/2024] Open
Abstract
BACKGROUND Accumulating evidence suggests that the gut microbiome is involved in the pathogenesis of insulin resistance (IR). However, the link between two of the most prevalent bowel disorders, chronic diarrhea and constipation, and the triglyceride glucose (TyG) index, a marker of IR, has not yet been investigated. AIM To investigate the potential association between TyG and the incidence of chronic diarrhea and constipation. METHODS This cross-sectional study enrolled 2400 participants from the National Health and Nutrition Examination Survey database from 2009-2010. TyG was used as an exposure variable, with chronic diarrhea and constipation as determined by the Bristol Stool Form Scale used as the outcome variables. A demographic investigation based on TyG quartile subgroups was performed. The application of multivariate logistic regression models and weighted generalized additive models revealed potential correlations between TyG, chronic diarrhea, and constipation. Subgroup analyses were performed to examine the stability of any potential associations. RESULTS In the chosen sample, chronic diarrhea had a prevalence of 8.00%, while chronic constipation had a prevalence of 8.04%. In multiple logistic regression, a more prominent positive association was found between TyG and chronic diarrhea, particularly in model 1 (OR = 1.45; 95%CI: 1.17-1.79, P = 0.0007) and model 2 (OR = 1.40; 95%CI: 1.12-1.76, P = 0.0033). No definite association was observed between the TyG levels and chronic constipation. The weighted generalized additive model findings suggested a more substantial positive association with chronic diarrhea when TyG was less than 9.63 (OR = 1.89; 95%CI: 1.05-3.41, P = 0.0344), and another positive association with chronic constipation when it was greater than 8.2 (OR = 1.74; 95%CI: 1.02-2.95, P = 0.0415). The results of the subgroup analyses further strengthen the extrapolation of these results to a wide range of populations. CONCLUSION Higher TyG levels were positively associated with abnormal bowel health.
Collapse
Affiliation(s)
- Jing-Yi Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Mu-Yun Liu
- Department of Gastroenterology, Navy No. 905 Hospital, Naval Medical University, Shanghai 200433, China
| | - Chang Sun
- Department of Gastroenterology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| |
Collapse
|
28
|
Staudacher HM, Mahoney S, Canale K, Opie RS, Loughman A, So D, Beswick L, Hair C, Jacka FN. Clinical trial: A Mediterranean diet is feasible and improves gastrointestinal and psychological symptoms in irritable bowel syndrome. Aliment Pharmacol Ther 2024; 59:492-503. [PMID: 37969059 DOI: 10.1111/apt.17791] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 09/17/2023] [Accepted: 10/20/2023] [Indexed: 11/17/2023]
Abstract
BACKGROUND Diet is fundamental to the care of irritable bowel syndrome (IBS). However, some approaches are not appropriate for individuals experiencing psychological symptoms. AIMS To assess feasibility of a Mediterranean diet in IBS and its impact on gastrointestinal and psychological symptoms. METHODS We recruited adults with Rome IV IBS and mild or moderate anxiety and/or depressive symptoms to an unblinded 6-week randomised controlled trial. Patients were randomised to Mediterranean diet counselling or habitual diet. We collected gastrointestinal and psychological symptom data, dietary data and stool samples for metagenomic sequencing. RESULTS We randomised 59 individuals (29 Mediterranean diet, 30 control); 48 completed the study. The Mediterranean Diet Adherence Screener score was higher in the Mediterranean diet group than controls at week 6 (7.5 [95% CI: 6.9-8.0] vs. 5.7 [5.2-6.3], p < 0.001), and there was a greater score increase than controls (2.1 [95% CI: 1.3-2.9] vs. 0.5 [95% CI: 0.1-1.0], p = 0.004), demonstrating Mediterranean diet feasibility. There was a greater proportion of gastrointestinal symptom responders in the Mediterranean diet group than controls (24/29, 83% vs. 11/30, 37%, p < 0.001) and depression responders (15/29, 52% vs. 6/30 20%, p = 0.015). There was no difference in FODMAP intake at week 6 (p = 0.51). Gastrointestinal adverse events were similar (p = 0.588). There were no differences in change in microbiome parameters between groups. CONCLUSIONS A Mediterranean diet is feasible in IBS and leads to improvement in gastrointestinal and psychological symptoms. Although this study was unblinded, these findings together with the broader benefits of the Mediterranean diet, provide strong impetus for future research in IBS. Australia New Zealand Clinical Trials Registry: ACTRN12620001362987.
Collapse
Affiliation(s)
- Heidi M Staudacher
- Food & Mood Centre, The Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine and Barwon Health, Deakin University, Geelong, Victoria, Australia
| | - Sophie Mahoney
- Food & Mood Centre, The Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine and Barwon Health, Deakin University, Geelong, Victoria, Australia
| | - Kim Canale
- Food & Mood Centre, The Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine and Barwon Health, Deakin University, Geelong, Victoria, Australia
| | - Rachelle S Opie
- Food & Mood Centre, The Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine and Barwon Health, Deakin University, Geelong, Victoria, Australia
| | - Amy Loughman
- Food & Mood Centre, The Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine and Barwon Health, Deakin University, Geelong, Victoria, Australia
| | - Daniel So
- Food & Mood Centre, The Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine and Barwon Health, Deakin University, Geelong, Victoria, Australia
- Department of Nutritional Sciences, King's College London, London, UK
| | - Lauren Beswick
- Department of Gastroenterology, Barwon Health, Geelong, Victoria, Australia
- School of Medicine, Deakin University, Geelong, Victoria, Australia
| | - Chris Hair
- Department of Gastroenterology, Barwon Health, Geelong, Victoria, Australia
- School of Medicine, Deakin University, Geelong, Victoria, Australia
| | - Felice N Jacka
- Food & Mood Centre, The Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine and Barwon Health, Deakin University, Geelong, Victoria, Australia
- Centre for Adolescent Health, Murdoch Children's Research Institute, Parkville, Victoria, Australia
| |
Collapse
|
29
|
Yamamoto S, Tsuchiya M, Iihara H, Hayasaki Y, Hori K, Kumakura Y, Watanabe D, Sakai H, Nakagawa S, Kudoh A, Oishi H, Kado N, Go M, Mashima K, Uchida T, Yasue M, Maeda A, Nishino K, Matsumoto K, Sato S, Ueda Y, Tomio K, Hayashi K, Takenaka M, Mori M, Kajiyama H, Bomoto Y, Suzuki S, Ishihara T, Suzuki A, Abe M. Proposal for Classifying the Emetogenicity of Oral Anticancer Agents with a Focus on PARP Inhibitors: A Prospective, Observational, Multicenter Study (JASCC-CINV 2002). J Cancer 2024; 15:1487-1497. [PMID: 38370375 PMCID: PMC10869979 DOI: 10.7150/jca.91675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Accepted: 01/16/2024] [Indexed: 02/20/2024] Open
Abstract
Background: Olaparib and niraparib (poly adenosine diphosphate [ADP]-ribose polymerase [PARP] inhibitors) have significant antitumor action in patients with ovarian cancer. However, the incidence of nausea and vomiting among patients on these drugs in clinical trials is rather high. There are no guidelines on antiemetic treatment for nausea caused by oral anticancer agents. This study aimed to investigate the incidence of nausea and vomiting caused by PARP inhibitors and the actual situation of antiemetic therapy in patients with gynecologic cancer. Methods: Patients with gynecologic cancer who were scheduled to receive PARP inhibitors were enrolled. Data on PARP inhibitor-induced nausea and vomiting were collected from patient diaries for 21 days. The primary endpoint was the incidence of vomiting during the 21 days after starting olaparib and niraparib. Results: Overall, between January 2020 and March 2023, 134 patients were enrolled. Of the 129 patients who were evaluated, 28 (21.7%) received prophylactic antiemetics for 21 days, and 101 (78.3%) did not. The overall incidence of PARP inhibitor-induced vomiting was 16.3%. The incidence of vomiting in the group that did not receive antiemetic prophylaxis was 13.9%. On dividing the group that did not receive antiemetic prophylaxis into the olaparib and niraparib subgroups, the incidence of vomiting was found to be 18.6% for the olaparib group and 10.3% for the niraparib group. Conclusion: The incidence of emesis without antiemetic prophylaxis among patients on olaparib and niraparib ranged from 10% to 30%. Therefore, olaparib and niraparib can be classified in the low emetogenic risk and prophylactic antiemetic therapy at the time of treatment initiation may be unnecessary.
Collapse
Affiliation(s)
- Senri Yamamoto
- Department of Pharmacy, Gifu University Hospital, 1-1 Yanagido, Gifu, Gifu, 501-1194, Japan
| | - Masami Tsuchiya
- Department of Pharmacy, Miyagi Cancer Center, 47-1 Nodayama, Medeshimashiote, Natori, Miyagi, 981-1293, Japan
| | - Hirotoshi Iihara
- Department of Pharmacy, Gifu University Hospital, 1-1 Yanagido, Gifu, Gifu, 501-1194, Japan
- Patient Safety Division, Gifu University Hospital, 1-1 Yanagido, Gifu, Gifu, 501-1194, Japan
- Laboratory of Community Pharmaceutical Practice and Science, Gifu Pharmaceutical University, 1-25-4 Daigakunishi, Gifu, Gifu, 501-1196, Japan
| | - Yoh Hayasaki
- Department of Obstetrics and Gynecology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, Gifu, 501-1194, Japan
| | - Kyoko Hori
- Department of Pharmacy, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan
| | - Yasuo Kumakura
- Department of Hospital Pharmacy, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya Aichi, 466-8560, Japan
| | - Daichi Watanabe
- Department of Pharmacy, Gifu University Hospital, 1-1 Yanagido, Gifu, Gifu, 501-1194, Japan
- Innovative and Clinical Research Promotion Center, Gifu University Hospital, 1-1 Yanagido, Gifu, Gifu, 501-1194, Japan
| | - Hideki Sakai
- Medical Oncology Division, Hyogo Cancer Center, 13-70, Kitaoji-cho, Akashi, Hyogo, 673-8558, Japan
| | - Satoshi Nakagawa
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita Osaka, 565-0871, Japan
| | - Akiko Kudoh
- Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, Tottori, 683-8504, Japan
| | - Hajime Oishi
- Department of Pharmacy, Gifu University Hospital, 1-1 Yanagido, Gifu, Gifu, 501-1194, Japan
| | - Nobuhiro Kado
- Department of Gynecology, Shizuoka Cancer Center 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Makiko Go
- Department of Pharmacy, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki Gifu, 503-0896, Japan
| | - Kota Mashima
- Department of Pharmacy, Fukuoka University Hospital, 7-45-1 Nanakuma, Jounanku, Fukuokashi, Fukuoka, 814-0180, Japan
| | - Takashi Uchida
- Department of Pharmacy, Miyagi Cancer Center, 47-1 Nodayama, Medeshimashiote, Natori, Miyagi, 981-1293, Japan
| | - Moeka Yasue
- Department of Pharmacy, Gifu University Hospital, 1-1 Yanagido, Gifu, Gifu, 501-1194, Japan
| | - Akimitsu Maeda
- Department of Pharmacy, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan
| | - Kimihiro Nishino
- Department of Healthcare Administration, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Koji Matsumoto
- Medical Oncology Division, Hyogo Cancer Center, 13-70, Kitaoji-cho, Akashi, Hyogo, 673-8558, Japan
| | - Shinya Sato
- Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, Tottori, 683-8504, Japan
| | - Yutaka Ueda
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita Osaka, 565-0871, Japan
| | - Kensuke Tomio
- Department of Obstetrics and Gynecology, Center Hospital of the National Center for Global Health and Medicine 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
| | - Katsuhisa Hayashi
- Department of Pharmacy, Miyagi Cancer Center, 47-1 Nodayama, Medeshimashiote, Natori, Miyagi, 981-1293, Japan
| | - Motoki Takenaka
- Department of Obstetrics and Gynecology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, Gifu, 501-1194, Japan
| | - Masahiko Mori
- Department of Gynecologic Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan
| | - Hiroaki Kajiyama
- Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Yoshimasa Bomoto
- Department of Obstetrics and Gynecology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, Gifu, 501-1194, Japan
| | - Shiro Suzuki
- Department of Gynecologic Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan
| | - Takuma Ishihara
- Innovative and Clinical Research Promotion Center, Gifu University Hospital, 1-1 Yanagido, Gifu, Gifu, 501-1194, Japan
| | - Akio Suzuki
- Department of Pharmacy, Gifu University Hospital, 1-1 Yanagido, Gifu, Gifu, 501-1194, Japan
- Laboratory of Advanced Medical Pharmacy, Gifu Pharmaceutical University, 1-25-4 Daigakunishi, Gifu, 501-1196, Japan
| | - Masakazu Abe
- Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu City, Shizuoka, 431-3192, Japan
| |
Collapse
|
30
|
Ravn S, Grønfeldt JM, Thaysen HV, Iversen LH. The impact of the extent of surgery on late adverse effects following cytoreductive surgery and HIPEC. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:107105. [PMID: 38096698 DOI: 10.1016/j.ejso.2023.107105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 09/07/2023] [Accepted: 09/28/2023] [Indexed: 01/16/2024]
Abstract
AIM To investigate the impact of the surgical extent on late adverse effects (LAE) following cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). METHOD A prospective cohort study including patients undergoing CRS + HIPEC due to peritoneal metastases from gastrointestinal tumour origin. From 2006 through 2019, consecutive patients treated with CRS + HIPEC were followed at 3, 6 and 12 months, and LAEs were assessed using the symptom scales and items from the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30). Surgical extent was categorized into three groups (major, intermediate, minor) based on peritonectomy procedures and colorectal resections performed as part of CRS. EORTC data were analysed using a linear mixed effects regression model adjusted for age, gender, origin of tumour and comorbidity. RESULTS In total, 257 patients who responded to at least one questionnaire during the follow-ups were included. Only diarrhoea symptoms were positively associated with surgical extent (mean differences: major vs. minor: 8.4 (-0.5; 17.2) (p = 0.06) and major vs. intermediate: 10.9 (3.8; 18.0) (p = 0.00)). Additionally, diarrhoea symptoms persisted throughout the study period and did not change over time (mean difference 12-3 months: -3.6 (-9.1; 1.7) (p-value = 0.18)). Overall, the levels of different symptom scales (fatigue, nausea and vomiting, pain, dyspnoea, and appetite loss) significantly decreased from 3 to 12 months. CONCLUSION Patients undergoing extensive CRS suffer from persistent impaired gastrointestinal function in terms of diarrhoea compared patients undergoing to less extensive surgery. Attention should be directed at detecting such LAE and to guide patients accordingly.
Collapse
Affiliation(s)
- Sissel Ravn
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark.
| | | | | | | |
Collapse
|
31
|
Tanihiro R, Yuki M, Sasai M, Haseda A, Kagami-Katsuyama H, Hirota T, Honma N, Nishihira J. Effects of Prebiotic Yeast Mannan on Gut Health and Sleep Quality in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Study. Nutrients 2023; 16:141. [PMID: 38201970 PMCID: PMC10780920 DOI: 10.3390/nu16010141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 12/28/2023] [Accepted: 12/29/2023] [Indexed: 01/12/2024] Open
Abstract
Human gut health is closely related to sleep. We aimed to evaluate the efficacy of yeast mannan (YM) in improving bowel habits and sleep quality, along with metabolomics in fecal samples. A total of 40 healthy adults (age range, 22-64 years) with discomfort in defecation were enrolled and randomly allocated to receive either YM (n = 20; 1.1 g/day) or placebo (n = 20) for four weeks. Participants recorded their defecation habits throughout the test periods. Sleep electroencephalogram (EEG) recording using an EEG device and fecal sampling were performed pre- and post-treatment. The YM group significantly increased defecation frequency and stool volumes compared to the placebo group. After 4 weeks of treatment, the non-REM sleep stage 3 (N3) duration in the YM group was significantly higher than that in the placebo group. YM ingestion significantly lengthened total time in bed (TIB) and significantly shortened N3 latency compared to placebo intake during the trial. The metabolomics analysis found a total of 20 metabolite differences between the YM and placebo groups. As a result of stepwise linear regression, changes in fecal propionate and gamma-aminobutyric acid (GABA) levels were identified as the primary factors explaining changes in TIB and N3 latency, respectively. Our findings suggest that the prebiotic YM could be beneficial to gut health and sleep quality.
Collapse
Affiliation(s)
- Reiko Tanihiro
- Core Technology Laboratories, Asahi Quality and Innovations, Ltd., Moriya 302-0106, Japan; (M.Y.); (M.S.); (T.H.)
| | - Masahiro Yuki
- Core Technology Laboratories, Asahi Quality and Innovations, Ltd., Moriya 302-0106, Japan; (M.Y.); (M.S.); (T.H.)
| | - Masaki Sasai
- Core Technology Laboratories, Asahi Quality and Innovations, Ltd., Moriya 302-0106, Japan; (M.Y.); (M.S.); (T.H.)
| | - Akane Haseda
- Department of Medical Management and Informatics, Hokkaido Information University, Ebetsu 069-8585, Japan (J.N.)
| | - Hiroyo Kagami-Katsuyama
- Department of Medical Management and Informatics, Hokkaido Information University, Ebetsu 069-8585, Japan (J.N.)
| | - Tatsuhiko Hirota
- Core Technology Laboratories, Asahi Quality and Innovations, Ltd., Moriya 302-0106, Japan; (M.Y.); (M.S.); (T.H.)
| | - Naoyuki Honma
- Department of Medical Management and Informatics, Hokkaido Information University, Ebetsu 069-8585, Japan (J.N.)
| | - Jun Nishihira
- Department of Medical Management and Informatics, Hokkaido Information University, Ebetsu 069-8585, Japan (J.N.)
| |
Collapse
|
32
|
Ruggiero L, Andretta V, Soldaini C, Fricano I, Mancusi M, Sellitti A, Vastarella J, Santonicola A. The Role of the Nurse in the Management of Irritable Bowel Syndrome: A Narrative Review. Transl Med UniSa 2023; 25:28-37. [PMID: 40303480 PMCID: PMC12038828 DOI: 10.37825/2239-9747.1043] [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: 10/23/2023] [Revised: 11/09/2023] [Accepted: 11/14/2023] [Indexed: 05/02/2025] Open
Abstract
Irritable bowel syndrome (IBS) is characterized by chronic symptoms of abdominal pain in association with changes in bowel habits. Abdominal pain is the most debilitating symptom for IBS patients, and its management is one of the greatest challenges for gastroenterologists. In recent years more evidence has arisen about an increasingly central role of the nurse in the management of gastrointestinal diseases including IBS. The aim of this narrative review is to analyse the latest evidence on the pathophysiology, diagnosis, and treatment of IBS patients with a specific focus on the role of the nurse in its management.
Collapse
Affiliation(s)
- Luigi Ruggiero
- Gastrointestinal Unit, Department of Medicine, Surgery and Dentistry
“Scuola Medica Salernitana”, University of Salerno, Baronissi, SA,
Italy
| | | | - Carlo Soldaini
- Gastrointestinal Unit, Department of Medicine, Surgery and Dentistry
“Scuola Medica Salernitana”, University of Salerno, Baronissi, SA,
Italy
| | - Ivan Fricano
- Gastrointestinal Unit, Department of Medicine, Surgery and Dentistry
“Scuola Medica Salernitana”, University of Salerno, Baronissi, SA,
Italy
| | - Marco Mancusi
- Gastrointestinal Unit, Department of Medicine, Surgery and Dentistry
“Scuola Medica Salernitana”, University of Salerno, Baronissi, SA,
Italy
| | - Annamaria Sellitti
- Gastrointestinal Unit, Department of Medicine, Surgery and Dentistry
“Scuola Medica Salernitana”, University of Salerno, Baronissi, SA,
Italy
| | - Josephine Vastarella
- Gastrointestinal Unit, Department of Medicine, Surgery and Dentistry
“Scuola Medica Salernitana”, University of Salerno, Baronissi, SA,
Italy
| | - Antonella Santonicola
- Gastrointestinal Unit, Department of Medicine, Surgery and Dentistry
“Scuola Medica Salernitana”, University of Salerno, Baronissi, SA,
Italy
| |
Collapse
|
33
|
Bar N, Karaa A, Kiser K, Kuo B, Zar-Kessler C. Gastrointestinal Sensory Neuropathy and Dysmotility in Fabry Disease: Presentations and Effect on Patient's Quality of Life. Clin Transl Gastroenterol 2023; 14:e00633. [PMID: 37578052 PMCID: PMC10749702 DOI: 10.14309/ctg.0000000000000633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 08/04/2023] [Indexed: 08/15/2023] Open
Abstract
INTRODUCTION Fabry disease is a rare multisystemic lysosomal disease resulting in variable manifestations of the gastrointestinal (GI), neurologic, cardiac, and renal systems. Whether GI manifestations are a result of gut dysmotility is undetermined. We aimed to explore GI manifestations in depth and their effect on patients with Fabry disease and to characterize gut motility. METHODS We recruited adult patients with Fabry disease reporting GI manifestations. All patients answered a battery of questionnaires covering symptom severity, GI-specific quality of life, and effects of work/productivity and underwent a wireless motility capsule test to measure pan-gut motility. RESULTS In 48 patients with Fabry disease, abnormal bowel habits and abdominal pain were the most common symptoms. Bloating, nausea, vomiting, and reflux were also prevalent. Neurologic manifestations were found in 95.8% of patients, along with their GI manifestations. Dysmotility was found in less than 35% of wireless motility capsule tests. Colon transit time was associated with constipation severity and Bristol Stool Scale. Several GI symptoms were associated with reduced quality of life, anxiety, and work/productivity, but not Fabry severity score. DISCUSSION This is the largest study of GI manifestations in patients with Fabry disease that characterizes gut motility. We found little association between GI manifestations and motility indices, suggesting that visceral hypersensitivity may be a major driver of symptoms. GI symptoms affect different aspects of patients' lives, yet are not always well-discussed or optimally managed in Fabry disease. Disease severity scores when used for therapeutic decision making do not often include GI symptoms or their impact.
Collapse
Affiliation(s)
- Nir Bar
- Center for Neurointestinal Health, Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Neurogastroenterology and Motility Service, Department of Gastroenterology and Hepatology, Tel Aviv Medical Center, Tel Aviv university school of medicine, Tel Aviv, Israel
| | - Amel Karaa
- Department of Genetics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Katheryn Kiser
- Center for Neurointestinal Health, Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Braden Kuo
- Center for Neurointestinal Health, Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Claire Zar-Kessler
- Center for Neurointestinal Health, Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
| |
Collapse
|
34
|
Crichton M, Marshall S, Marx W, Isenring E, Vázquez-Campos X, Dawson SL, Lohning A. Effect of Ginger Root Powder on Gastrointestinal Bacteria Composition, Gastrointestinal Symptoms, Mental Health, Fatigue, and Quality of Life: A Double-Blind Placebo-Controlled Trial. J Nutr 2023; 153:3193-3206. [PMID: 37690779 DOI: 10.1016/j.tjnut.2023.09.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 08/02/2023] [Accepted: 09/01/2023] [Indexed: 09/12/2023] Open
Abstract
BACKGROUND Despite compositional alterations in gastrointestinal microbiota being purported to underpin some of the therapeutic effects of ginger, the effect of a standardized ginger supplement on gut microbiota has not been tested in humans. OBJECTIVES To determine the effect of a standardized ginger (Zingiber officinale) root powder, compared to placebo, on gastrointestinal bacteria and associated outcomes in healthy adults. METHODS A randomized double-blind placebo-controlled trial allocated participants aged 18 to 30 y to ginger or microcrystalline cellulose (MCC) placebo. The intervention comprised 1.2 g/d of ginger (4 capsules per day totaling 84 mg/d of active gingerols/shogaols) for 14 d following a 1-wk run-in period. Primary outcomes were gastrointestinal community composition, alpha and beta diversity, and differential abundance, measured using 16S rRNA gene sequencing of fecal samples. Secondary outcomes were gastrointestinal symptoms, bowel function, depression, anxiety, stress, fatigue, quality of life, and adverse events. RESULTS Fifty-one participants were enrolled and analyzed (71% female; mean age 25 ± 3 y; ginger: n = 29, placebo: n = 22). There was a greater increase in relative abundance of phylum, Actinobacteria, observed following ginger supplementation compared to placebo (U: 145.0; z: -2.1; P = 0.033). Ginger was associated with a greater abundance of the genera Parabacteroides, Bacillus, Ruminococcaceae incertae sedis, unclassified Bacilli, families Defluviitaleaceae, Morganellaceae, and Bacillaceae as well as lower abundance of the genus Blautia and family Sphingomonadaceae (P < 0.05). An improvement in indigestion symptoms was observed with ginger supplementation (U: 196.0; z: -2.4; P = 0.015). No differences between ginger and placebo groups were found for alpha and beta diversity or other secondary outcomes. No moderate or severe adverse events were reported. CONCLUSIONS Supplementation with ginger root powder was safe and altered aspects of gastrointestinal bacteria composition; however, it did not change alpha- or beta diversity, bowel function, gastrointestinal symptoms, mood, or quality of life in healthy adults. These results provide further understanding regarding the mechanisms of action of ginger supplementation. This trial was registered in the Australia New Zealand Clinical Trials Registry as ACTRN12620000302954p and the Therapeutic Goods Administration as CT-2020-CTN-00380-1.
Collapse
Affiliation(s)
- Megan Crichton
- Bond University Nutrition and Dietetics Research Group, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia; Cancer and Palliative Care Outcomes Centre, Centre for Healthcare Transformation, School of Nursing, Faculty of Health, Kelvin Grove, Queensland, Australia.
| | - Skye Marshall
- Bond University Nutrition and Dietetics Research Group, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia; Research Institute for Future Health, Gold Coast, Queensland, Australia
| | - Wolfgang Marx
- Bond University Nutrition and Dietetics Research Group, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia; Deakin University, Food & Mood Centre, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Geelong, Victoria, Australia
| | - Elizabeth Isenring
- Bond University Nutrition and Dietetics Research Group, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia
| | - Xabier Vázquez-Campos
- NSW Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Kensington, New South Wales, Australia
| | - Samantha L Dawson
- Deakin University, Food & Mood Centre, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Geelong, Victoria, Australia
| | - Anna Lohning
- Bond University Nutrition and Dietetics Research Group, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia
| |
Collapse
|
35
|
Mizutani Y, Kawamoto S, Takahashi M, Doi H, Wakida K, Tabuchi S, Tanda M, Soga A, Chijiki R, Takakura H, Kawaguchi K, Higashime A, Watanabe M, Ichikawa H, Matsumoto S, Sakai R, Goto H, Kurata K, Kakiuchi S, Miyata Y, Uryu K, Inui Y, Kitao A, Yakushijin K, Matsuoka H, Minami H. Efficacy and Safety of Synbiotics in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Randomized, Double-blinded, Placebo-controlled Pilot Study. Intern Med 2023; 62:2949-2958. [PMID: 36792187 PMCID: PMC10641206 DOI: 10.2169/internalmedicine.1314-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 12/26/2022] [Indexed: 02/16/2023] Open
Abstract
Objective High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective treatment option for relapsed and refractory aggressive malignant lymphoma. However, patients frequently experience treatment-induced gastrointestinal symptoms. Synbiotics, including live microorganisms and nondigestible food ingredients, reportedly ameliorate chemotherapy-induced mucosal damage. In this study, we assessed the efficacy and safety of synbiotics in patients undergoing auto-HSCT. Methods This randomized, double-blinded study included patients with malignant lymphoma eligible for auto-HSCT. The patients were randomly assigned to either a synbiotic group receiving Bifidobacterium longum (BB536) and guar gum or a placebo group receiving a placebo containing dextrin. The supplements were administered twice daily from the start of conditioning chemotherapy up to 28 days after auto-HSCT. The primary endpoint was the duration of total parenteral nutrition (TPN). Results In total, 12 patients were included and randomized. The median duration of TPN was 15 (range, 12-33) days in the synbiotic group and 17.5 (range, 0-32) days in the placebo group. The median duration of grade ≥3 diarrhea was shorter in the synbiotic group than in then placebo group (2.5 vs. 6.5 days), as was the duration of hospital stay (31.5 vs. 43 days). The oral intake and quality of life regarding diarrhea and anorexia improved in the synbiotic group after engraftment. Synbiotic infections, including bacteremia, were not observed. Conclusion Synbiotics may reduce gastrointestinal toxicity, thereby reducing nutritional problems and improving the quality of life of patients undergoing auto-HSCT, without severe adverse events.
Collapse
Affiliation(s)
- Yu Mizutani
- Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine and Hospital, Japan
| | - Shinichiro Kawamoto
- Department of Transfusion Medicine and Cell Therapy, Kobe University Hospital, Japan
| | | | - Hisayo Doi
- Division of Nursing, Kobe University Hospital, Japan
| | - Kumiko Wakida
- Division of Nutrition, Kobe University Hospital, Japan
| | | | - Masaaki Tanda
- Department of Pharmacy, Kobe University Hospital, Japan
| | - Akihiro Soga
- Department of Pharmacy, Kobe University Hospital, Japan
| | - Ruri Chijiki
- Department of Medical Oncology/Hematology, Kobe University Hospital, Japan
| | - Hidetomo Takakura
- Department of Medical Oncology/Hematology, Kobe University Hospital, Japan
| | - Koji Kawaguchi
- Department of Medical Oncology/Hematology, Kobe University Hospital, Japan
| | - Ako Higashime
- Department of Medical Oncology/Hematology, Kobe University Hospital, Japan
| | - Marika Watanabe
- Department of Medical Oncology/Hematology, Kobe University Hospital, Japan
| | - Hiroya Ichikawa
- Department of Medical Oncology/Hematology, Kobe University Hospital, Japan
| | - Sakuya Matsumoto
- Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine and Hospital, Japan
| | - Rina Sakai
- Department of Medical Oncology/Hematology, Kobe University Hospital, Japan
| | - Hideaki Goto
- Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine and Hospital, Japan
| | - Keiji Kurata
- Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine and Hospital, Japan
| | - Seiji Kakiuchi
- Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine and Hospital, Japan
| | - Yoshiharu Miyata
- Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine and Hospital, Japan
| | - Kiyoaki Uryu
- Department of Medical Oncology/Hematology, Kobe University Hospital, Japan
| | - Yumiko Inui
- Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine and Hospital, Japan
| | - Akihito Kitao
- Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine and Hospital, Japan
| | - Kimikazu Yakushijin
- Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine and Hospital, Japan
| | - Hiroshi Matsuoka
- Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine and Hospital, Japan
| | - Hironobu Minami
- Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine and Hospital, Japan
| |
Collapse
|
36
|
Zandalasini M, Pelizzari L, Ciardi G, Giraudo D, Guasconi M, Paravati S, Lamberti G, Frizziero A. Bowel dysfunctions after acquired brain injury: a scoping review. Front Hum Neurosci 2023; 17:1146054. [PMID: 37900728 PMCID: PMC10602674 DOI: 10.3389/fnhum.2023.1146054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 09/25/2023] [Indexed: 10/31/2023] Open
Abstract
Bowel dysfunction is a common consequence of neurological diseases and has a major impact on the dignity and quality of life of patients. Evidence on neurogenic bowel is focused on spinal cord injury and multiple sclerosis; few studies have focused on patients with acquired brain injury (ABI). Neurogenic bowel dysfunction is related to a lifelong condition derived from central neurological disease, which further increases disability and social deprivation. The manifestations of neurogenic bowel dysfunction include fecal incontinence and constipation. Almost two out of three patients with central nervous system disorder have bowel impairment. This scoping review aims to comprehend the extent and type of evidence on bowel dysfunction after ABI and present conservative treatment. For this scoping review, the PCC (population, concept, and context) framework was used: patients with ABI and bowel dysfunction; evaluation and treatment; and intensive/extensive rehabilitation path. Ten full-text articles were included in the review. Oral laxatives are the most common treatment. The Functional Independence Measure (FIM) subscale is the most common scale used to assess neurogenic bowel disease (60%), followed by the Rome II and III criteria, and the colon transit time is used to test for constipation; however, no instrumental methods have been used for incontinence. An overlapping between incontinence and constipation, SCI and ABI increase difficulties to manage NBD. The need for a consensus between the rehabilitative and gastroenterological societies on the diagnosis and medical care of NBD. Systematic review registration Open Science Framework on August 16, 2022 https://doi.org/10.17605/OSF.IO/NEQMA.
Collapse
Affiliation(s)
- Matteo Zandalasini
- Department of Rehabilitative Medicine, Azienda USL Piacenza, Piacenza, Italy
| | - Laura Pelizzari
- Department of Rehabilitative Medicine, Azienda USL Piacenza, Piacenza, Italy
| | - Gianluca Ciardi
- Department of Rehabilitative Medicine, Azienda USL Piacenza, Piacenza, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Donatella Giraudo
- Department of Urology, San Raffaele Hospital, Ville Turro, Milan, Italy
| | - Massimo Guasconi
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Dipartimento della Direzione delle Professioni Sanitarie, Azienda USL Piacenza, Piacenza, Italy
| | - Stefano Paravati
- Department of Rehabilitative Medicine, Azienda USL Piacenza, Piacenza, Italy
| | - Gianfranco Lamberti
- Department of Rehabilitative Medicine, Azienda USL Piacenza, Piacenza, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Antonio Frizziero
- Department of Rehabilitative Medicine, Azienda USL Piacenza, Piacenza, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| |
Collapse
|
37
|
Bourre B, Desprez C, Gourcerol G, Tavolacci MP, Duflot T, Leroi AM. Multiple sclerosis and bowel symptoms: Frequency and barriers to their management. Mult Scler Relat Disord 2023; 78:104919. [PMID: 37579644 DOI: 10.1016/j.msard.2023.104919] [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: 04/14/2023] [Revised: 07/16/2023] [Accepted: 07/28/2023] [Indexed: 08/16/2023]
Abstract
BACKGROUND The frequency of bowel symptoms (BSs) is still a matter for debate in multiple sclerosis (MS) patients. However, BSs have been shown to cause significant distress. Our study aimed to (i) investigate the frequency of BSs, particularly those that are not managed, (ii) identify potential predictors for help-seeking care for patients with BSs, and (iii) evaluate the ability of the Neurogenic Bowel Dysfunction (NBD) score to screen for BSs. METHOD Three hundred sixty-nine MS patients completed a cross-sectional demographic and clinical survey of MS and BSs and their management. RESULTS BSs were reported by 47.7% of MS patients. Eighty-eight percent of MS patients had a very minor-minor Neurogenic Bowel Disorder (NBD) score and 12% had a moderate-severe NBD score. Forty-one percent of patients did not report their BS to a healthcare provider, mainly because they preferred not to talk about the problem. BS duration was the only significant predictor of help-seeking for BS management. Female sex, visual impairment, a digestive history, and longer MS duration were good predictors of BSs. Patients with BSs (86%) were correctly identified with an NBD score >2. CONCLUSION BSs are under-detected in MS populations. This is partially related to non-declaration by patients. Targeting BSs using the NBD score is a good way to increase reporting.
Collapse
Affiliation(s)
- Bertrand Bourre
- Department of Neurology, CHU Rouen, CIC-CRB 1404, Rouen F-76000, France
| | - Charlotte Desprez
- Department of Digestive Physiology, CHU Rouen, CIC-CRB 1404, Rouen University Normandie, INSERM, ADEN UMR 1073, F-76000, Rouen, France
| | - Guillaume Gourcerol
- Department of Digestive Physiology, CHU Rouen, CIC-CRB 1404, Rouen University Normandie, INSERM, ADEN UMR 1073, F-76000, Rouen, France
| | - Marie-Pierre Tavolacci
- Department of Epidemiology, CHU Rouen, CIC-CRB 1404, Rouen University Normandie, INSERM, ADEN UMR 1073, F-76000, Rouen, France
| | - Thomas Duflot
- Department of Pharmacology, Endothelium, Valvulopathy, and Heart Failure, CHU Rouen, CIC-CRB 1404, University Rouen Normandie, INSERM, EnVI UMR1096, F-76000, Rouen, France
| | - Anne-Marie Leroi
- Department of Digestive Physiology, CHU Rouen, CIC-CRB 1404, Rouen University Normandie, INSERM, ADEN UMR 1073, F-76000, Rouen, France.
| |
Collapse
|
38
|
Malinowska AM, Majcher M, Hooiveld GJ, Przydatek H, Szaban M, Kurowiecka A, Schmidt M. Experimental Capacity of Human Fecal Microbiota to Degrade Fiber and Produce Short-Chain Fatty Acids Is Associated with Diet Quality and Anthropometric Parameters. J Nutr 2023; 153:2827-2841. [PMID: 37573016 DOI: 10.1016/j.tjnut.2023.08.007] [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: 05/22/2023] [Revised: 07/17/2023] [Accepted: 08/03/2023] [Indexed: 08/14/2023] Open
Abstract
BACKGROUND Short-chain fatty acids (SCFAs) are considered beneficial to human health. The associations between bacterial capacity to produce SCFAs, diet, and health are not fully understood. OBJECTIVE We aimed to evaluate the capacity of human fecal microbiota to produce SCFAs and to metabolize soluble and insoluble fiber and to study its associations with human diet, anthropometric parameters, and carbohydrate and lipid metabolism. METHODS A cross-sectional study was carried out with 200 adult participants. Diet was evaluated using food records. Capacity to produce acetate, butyrate, and propionate and to degrade soluble fiber were assessed in an ex vivo experiment where fecal samples were inoculated in a pectin-containing broth. Fecal β-glucosidase activity was measured to assess potential to degrade insoluble fiber. RESULTS The main dietary determinants of high capacity to metabolize fiber were high intake of vegetables, fruits, nuts, and seeds. After adjusting analyses for confounders, glucose and lipid parameters were not significantly associated with any of the studied microbial capacities, but the capacity to produce propionic acid was significantly associated with hip circumference (β = -0.018, P = 0.044), which was seen especially in people eating healthy. CONCLUSIONS We confirmed that high intake of fiber-rich products is positively associated with the capacity of fecal microbiota to degrade soluble and insoluble dietary fiber and that people eating healthy food might benefit from enhanced microbial capacity to produce propionic acid.
Collapse
Affiliation(s)
- Anna M Malinowska
- Department of Human Nutrition and Dietetics, Poznań University of Life Sciences, Poznań, Poland; Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.
| | - Malgorzata Majcher
- Department of Food Chemistry and Instrumental Analysis, Poznań University of Life Sciences, Poznań, Poland
| | - Guido Jej Hooiveld
- Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands
| | - Hanna Przydatek
- Department of Human Nutrition and Dietetics, Poznań University of Life Sciences, Poznań, Poland
| | - Marta Szaban
- Department of Human Nutrition and Dietetics, Poznań University of Life Sciences, Poznań, Poland
| | - Agata Kurowiecka
- Department of Human Nutrition and Dietetics, Poznań University of Life Sciences, Poznań, Poland
| | - Marcin Schmidt
- Department of Food Biotechnology and Microbiology, Poznań University of Life Sciences, Poznań, Poland
| |
Collapse
|
39
|
Bräuner AB, Avellaneda N, Christensen P, Drewes AM, Emmertsen KJ, Krogh K, Laurberg S, Lauritzen MB, Løve US, Thorlacius-Ussing O, Juul T. Prospective evaluation of bowel function and quality of life after colon cancer surgery - is it time for routine screening for late sequelae? Acta Oncol 2023; 62:1132-1142. [PMID: 37589432 DOI: 10.1080/0284186x.2023.2246102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 08/02/2023] [Indexed: 08/18/2023]
Abstract
AIM Bowel dysfunction after colon cancer (CC) surgery is widely neglected in current follow up programmes. This study explored changes in bowel function and quality of life (QoL) from three (3 m) to twelve months (12 m) after surgery in CC patients undergoing right- or left-sided colon resection (RightSCR/LeftSCR) and investigated differences between the two groups 12 m after surgery. METHOD CC patients undergoing surgical resection in 2018-2020 at five surgical departments were included in this population-based prospective cohort study. Included patients completed electronic surveys consisting of a collection of validated scores 3 m and 12 m after surgery. RESULTS A total of 708 CC patients (423 RightSCR, 285 LeftSCR) were included. In RightSCR, no improvement was observed from 3 m to 12 m in most scores/items, on the contrary, symptom worsening in flatus- and faecal incontinence and urgency was observed (p < 0.05). Also, the proportion of patients rating their bowel function as very good/good decreased (p < 0.05) in this group. In LeftSCR improvement was found in flatus and faecal incontinence, urgency and night-time defaecation (p < 0.02), while no improvement was observed in the remaining scores/items. At 12 m, higher proportions of RightSCR than LeftSCR reported loose stools, incontinence and urgency (all p < 0.001), whereas LeftSCR more often reported hard stools and flatus incontinence (p < 0.05). Among all CC patients 18.3% reported bowel-related impairment of QoL at 12 m with no differences between the two groups. CONCLUSION From 3 m to 12 m no significant change was observed in the majority of bowel function and QoL scores/items, however, some symptoms worsened in RightSCR, while a few improved in LeftSCR. Bowel dysfunction and impaired QoL were still common in both groups at 12 m, although the symptom pattern differed between the groups. These findings call for a systematic screening for bowel dysfunction to ensure early treatment of symptoms.
Collapse
Affiliation(s)
- Annette Boesen Bräuner
- Department of Surgery, Regional Hospital Viborg, Viborg, Denmark
- Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects After Cancer in the Pelvic Organs, Aalborg, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Nicolas Avellaneda
- General Surgical Department, Centro de Educación Médica e Investigaciones Clínicas "Noberto Quirno" (CEMIC), Buenos Aires, Argentina
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
| | - Peter Christensen
- Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects After Cancer in the Pelvic Organs, Aalborg, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
| | - Asbjørn Mohr Drewes
- Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects After Cancer in the Pelvic Organs, Aalborg, Denmark
- Mech-Sense. Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Katrine Jøssing Emmertsen
- Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects After Cancer in the Pelvic Organs, Aalborg, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Surgery, Regional Hospital Randers, Randers, Denmark
| | - Klaus Krogh
- Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects After Cancer in the Pelvic Organs, Aalborg, Denmark
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Søren Laurberg
- Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects After Cancer in the Pelvic Organs, Aalborg, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Michael Bødker Lauritzen
- Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects After Cancer in the Pelvic Organs, Aalborg, Denmark
- Department of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, Denmark
| | - Uffe Schou Løve
- Department of Surgery, Regional Hospital Viborg, Viborg, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Ole Thorlacius-Ussing
- Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects After Cancer in the Pelvic Organs, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Department of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, Denmark
| | - Therese Juul
- Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects After Cancer in the Pelvic Organs, Aalborg, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
| |
Collapse
|
40
|
Ferris A, Gaisinskaya P, Nandi N. Approach to Diarrhea. Prim Care 2023; 50:447-459. [PMID: 37516513 DOI: 10.1016/j.pop.2023.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/31/2023]
Abstract
Diarrhea is a common complaint in primary care offices. It affects the patient's quality of life and increases health care resource utilization. Although most cases of diarrhea are acute and self-limiting, there are multiple causes that can lead to serious morbidity and mortality. Likewise, chronic diarrhea can be a sign of a more serious condition and requires thoughtful evaluation. Ultimately, primary care physicians must take an evidence-based and comprehensive approach to diarrhea to appropriately apply health care resources in the interest of patient care.
Collapse
Affiliation(s)
- Allison Ferris
- Internal Medicine Residency Program, Department of Medicine, Charles E. Schmidt College of Medicine, Florida Atlantic University, 800 Meadows Road, Boca Raton, FL 33486, USA.
| | - Polina Gaisinskaya
- Internal Medicine Residency Program, Department of Medicine, Charles E. Schmidt College of Medicine, Graduate Medical Education Consortium, Bethesda Hospital, Boca Raton Regional Hospital, Delray Medical Center, Florida Atlantic University, 800 Meadows Road, Boca Raton, FL 33486, USA
| | - Neilanjan Nandi
- Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, 3737 Market Street, 11th floor, Philadelphia, PA 19104, USA
| |
Collapse
|
41
|
Aikawa G, Ouchi A, Sakuramoto H, Hoshino T, Enomoto Y, Shimojo N, Inoue Y. Association of early-onset constipation and diarrhoea with patient outcomes in critically ill ventilated patients: A retrospective observational cohort study. Aust Crit Care 2023; 36:737-742. [PMID: 36400625 DOI: 10.1016/j.aucc.2022.10.005] [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: 04/17/2022] [Revised: 09/21/2022] [Accepted: 10/03/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Constipation and diarrhoea are closely related, but few studies have examined them simultaneously. OBJECTIVES The purpose of this study was to describe patient defecation status after intensive care unit (ICU) admission and determine the association between early-onset constipation and diarrhoea following ICU admission with outcomes for critically ill ventilated patients. METHODS Patients ventilated for ≥48 h in an ICU were retrospectively investigated, and their defecation status was assessed during the first week after admission. Early-onset constipation and diarrhoea were defined as onset during the first week of ICU admission. The patients were divided into three groups-normal defecation, constipation, and diarrhoea-and multiple comparisons were performed using the Kruskal-Wallis test and the Mann-Whitney U test with Bonferroni adjustment. Additionally, multivariable analysis was performed for mortality and length of stay using the linear and logistic regression models. RESULTS Of the 85 critically ill ventilated patients, 47 (55%) experienced early-onset constipation and 12 (14%) experienced early-onset diarrhoea. Patients with normal defecation and diarrhoea increased from the 4th and 5th day of ICU admission. Early-onset diarrhoea was significantly associated with the length of ICU stay (B = 7.534, 95% confidence interval: 0.116-14.951). CONCLUSIONS Early-onset constipation and diarrhoea were common in critically ill ventilated patients, and early-onset diarrhoea was associated with the length of ICU stay.
Collapse
Affiliation(s)
- Gen Aikawa
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan; Intensive Care Unit, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki, Japan.
| | - Akira Ouchi
- Department of Adult Health Nursing, College of Nursing, Ibaraki Christian University, 6-11-1 Omika, Hitachi, Ibaraki, Japan
| | - Hideaki Sakuramoto
- Department of Critical Care and Disaster Nursing, Japanese Red Cross Kyushu International College of Nursing, 1-1 Asty, Munakata, Fukuoka, Japan
| | - Tetsuya Hoshino
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
| | - Yuki Enomoto
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
| | - Nobutake Shimojo
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
| | - Yoshiaki Inoue
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan
| |
Collapse
|
42
|
Zheng Y, Xu L, Zhang S, Liu Y, Ni J, Xiao G. Effect of a probiotic formula on gastrointestinal health, immune responses and metabolic health in adults with functional constipation or functional diarrhea. Front Nutr 2023; 10:1196625. [PMID: 37497057 PMCID: PMC10368241 DOI: 10.3389/fnut.2023.1196625] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 06/05/2023] [Indexed: 07/28/2023] Open
Abstract
Objective Our aim was to determine the efficacy of four-week probiotic supplementation on gastrointestinal health. The secondary objectives were to assess probiotic effects on immune reaction, as well as weight control and metabolic health. Methods We conducted two randomized sub-trials, respectively, among subjects who were diagnosed with functional constipation (FC) or functional diarrhea (FDr) according to the Rome IV criteria. In each sub-trial, 70 eligible Chinese adults were randomized to receive a multi-strain probiotic combination or a placebo. Gastrointestinal symptoms, defecation habits, stool characteristics, blood and fecal biochemistry markers, anthropometrics measures, stress-associated responses, and intestinal flora changes were assessed at baseline and after probiotics intervention. Results Four weeks of probiotic supplementation reduced overall gastrointestinal symptoms scores in FC participants (p < 0.0001). Their mean weekly stool frequency increased from 3.3 times to 6.2 times; immune response and inflammation markers improved with increases in serum IgA, IFN-γ and fecal sIgA, and decrease in hsCRP; most components of lipid profile were significantly ameliorated, with increases in HDL-C and reductions in TC and TG; body weight, body mass index and basal metabolic rate decreased following probiotics consumption. For FDr participants, probiotics consumption markedly reduced overall gastrointestinal symptom scores (p < 0.0001); decreased stool frequency by 3 times per week; increased IgA, IFN-γ, sIgA concentrations, while lowered hsCRP and IL-4 levels. Both FC and FDr participants had improvement in the scores of defecation habits, anxiety or depression, and perceived stress. Probiotics supplementation promoted the production of all three major short-chain fatty acids. No changes were observed in LDL-C, IgG, IgM, IL-8, IL-10 and motilin. Conclusion Supplementation with the probiotic formula over a four-week period could help relieving gastrointestinal symptoms, improving satisfaction with defecation habits, emotional state and immune response, and ameliorating dysbacteriosis in participants with FC or FDr. It also had beneficial effects on lipid metabolism and weight control for FC participants.
Collapse
Affiliation(s)
- Yanyi Zheng
- Shenzhen Precision Health Food Technology Co., Ltd., Shenzhen, China
| | - Leiming Xu
- Department of Gastroenterology, Shanghai Jiaotong University Affiliated Xinhua Hospital, Shanghai, China
| | - Silu Zhang
- Shenzhen Precision Health Food Technology Co., Ltd., Shenzhen, China
| | - Yanwen Liu
- School of Bioengineering, East China University of Science and Technology, Shanghai, China
| | - Jiayi Ni
- Sprim (China) Consulting Co. Ltd., Shanghai, China
| | - Guoxun Xiao
- Shenzhen Precision Health Food Technology Co., Ltd., Shenzhen, China
| |
Collapse
|
43
|
Gonzalez-Mercado VJ, Lim J, Aouizerat B. Insights from Bacterial 16S rRNA Gene into Bacterial Genera and Predicted Metabolic Pathways Associated with Stool Consistency in Rectal Cancer Patients: A Proof of Concept. Biol Res Nurs 2023; 25:491-500. [PMID: 36859821 PMCID: PMC10404905 DOI: 10.1177/10998004231159623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/03/2023]
Abstract
PURPOSE To examine if gut microbial taxa abundances and predicted functional pathways correlate with Bristol Stool Form Scale (BSFS) classification at the end of neoadjuvant chemotherapy and radiation therapy (CRT) for rectal cancer. METHODS Rectal cancer patients (n = 39) provided stool samples for 16S rRNA gene sequencing. Stool consistency was evaluated using the BSFS. Gut microbiome data were analyzed using QIIME2. Correlation analysis were performed in R. RESULTS At the genus level, Staphylococcus positively correlates (Spearman's rho = 0.26), while Anaerofustis, Roseburia, Peptostreptococcaceae unclassified, Ruminococcaceae UBA1819, Shuttleworthia, Ca. Soleaferrea, Anaerostignum, Oscillibacter, and Akkermansia negatively correlate with BSFS scores (Spearman's rho -0.20 to -0.42). Predicted pathways, including mycothiol biosynthesis and sucrose degradation III (sucrose invertase), were positively correlated with BSFS (Spearman's rho = 0.03-0.21). CONCLUSION The data support that in rectal cancer patients, stool consistency is an important factor to include in microbiome studies. Loose/liquid stools may be linked to Staphylococcus abundance and to mycothiol biosynthesis and sucrose degradation pathways.
Collapse
Affiliation(s)
| | - Jean Lim
- University of South Florida Tampa Campus, Tampa, FL, USA
| | - Bradley Aouizerat
- Department of Oral and Maxillofacial Surgery, New York University, New York, NY, USA
| |
Collapse
|
44
|
Johansen OE, Curti D, von Eynatten M, Rytz A, Lahiry A, Delodder F, Ufheil G, D'Urzo C, Orengo A, Thorne K, Lerea-Antes JS. Oligomalt, a New Slowly Digestible Carbohydrate, Is Well Tolerated in Healthy Young Men and Women at Intakes Up to 180 Gram per Day: A Randomized, Double-Blind, Crossover Trial. Nutrients 2023; 15:2752. [PMID: 37375656 DOI: 10.3390/nu15122752] [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: 05/15/2023] [Revised: 06/01/2023] [Accepted: 06/06/2023] [Indexed: 06/29/2023] Open
Abstract
In this randomized, double-blind triple-crossover study (NCT05142137), the digestive tolerance and safety of a novel, slowly digestible carbohydrate (SDC), oligomalt, an α-1,3/α-1,6-glucan α-glucose-based polymer, was assessed in healthy adults over three separate 7-day periods, comparing a high dose of oligomalt (180 g/day) or a moderate dose of oligomalt (80 g/day in combination with 100 g maltodextrin/day) with maltodextrin (180 g/day), provided as four daily servings in 300 mL of water with a meal. Each period was followed by a one-week washout. A total of 24 subjects (15 females, age 34 years, BMI 22.2 kg/m2, fasting blood glucose 4.9 mmol/L) were recruited, of whom 22 completed the course. The effects on the primary endpoint (the Gastrointestinal Symptom Rating Score (GSRS)) showed a statistically significant dose dependency, albeit of limited clinical relevance, between a high dose of oligomalt and maltodextrin (mean (95% CI) 2.29 [2.04, 2.54] vs. 1.59 [1.34, 1.83], respectively; difference: [-1.01, -0.4], p < 0.0001), driven by the GSRS-subdomains "Indigestion" and "Abdominal pain". The GSRS difference ameliorated with product exposure, and the GSRS in those who received high-dose oligomalt as their third intervention period was similar to pre-intervention (mean ± standard deviation: 1.6 ± 0.4 and 1.4 ± 0.3, respectively). Oligomalt did not have a clinically meaningful impact on the Bristol Stool Scale, and it did not cause serious adverse events. These results support the use of oligomalt across various doses as an SDC in healthy, normal weight, young adults.
Collapse
Affiliation(s)
| | | | | | - Andreas Rytz
- Nestlé Research, Clinical Research Unit, 1000 Lausanne, Switzerland
| | - Anirban Lahiry
- Nestlé Research, Clinical Research Unit, 1000 Lausanne, Switzerland
| | | | - Gerhard Ufheil
- Nestlé Research and Development Konolfingen, Société des Produits Nestlé S.A., 3510 Konolfingen, Switzerland
- Nestlé Product Technology Center NHS, Société des Produits Nestlé S.A., Bridgewater, NJ 08807, USA
| | | | - Audrey Orengo
- Société des Produits Nestlé, 1000 Lausanne, Switzerland
| | - Kate Thorne
- Nestlé Health Science, 1000 Lausanne, Switzerland
| | - Jaclyn S Lerea-Antes
- Nestlé Product Technology Center NHS, Société des Produits Nestlé S.A., Bridgewater, NJ 08807, USA
- Nestlé Health Science, Bridgewater, NJ 08807, USA
| |
Collapse
|
45
|
Durgam N, Dashputre AA, Moshkovich O, Rezaie A, Martinez N, Enayati P, Stansbury J, Joseph G. Content validation of a daily patient-reported outcome measure for assessing symptoms in patients with Small Intestinal Bacterial Overgrowth. Qual Life Res 2023:10.1007/s11136-023-03407-z. [PMID: 37212941 PMCID: PMC10393850 DOI: 10.1007/s11136-023-03407-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/16/2023] [Indexed: 05/23/2023]
Abstract
PURPOSE The aim of this study was to generate evidence supporting the development and content validity of a new PRO instrument, the Small Intestinal Bacterial Overgrowth (SIBO) Symptom Measure (SSM) daily diary. The SSM assesses symptom severity in SIBO patients, with the ultimate goal of providing a fit for purpose PRO for endpoint measurement. METHODS Qualitative research included 35 SIBO patients in three study stages, using a hybrid concept elicitation (CE)/cognitive interview (CI) method with US patients, ≥ 18 years. Stage 1 included a literature review, clinician interviews, and initial CE interviews with SIBO patients to identify symptoms important to patients for inclusion in the SSM. Stage 2 included hybrid CE/CI to learn more about patients' SIBO experience and test the draft SSM. Finally, stage 3 used CIs to refine the instrument and test its content validity. RESULTS In stage 1 (n = 8), 15 relevant concepts were identified, with items drafted based on the literature review/clinician interviews and elicitation work. Within stage 2 (n = 15), the SSM was refined to include 11 items; with wording revised for three items. Stage 3 (n = 12) confirmed the comprehensiveness of the SSM, as well as appropriateness of the item wording, recall period, and response scale. The resulting 11-item SSM assesses the severity of bloating, abdominal distention, abdominal discomfort, abdominal pain, flatulence, physical tiredness, nausea, diarrhea, constipation, appetite loss, and belching. CONCLUSIONS This study provides evidence supporting the content validity of the new PRO. Comprehensive patient input ensures that the SSM is a well-defined measure of SIBO, ready for psychometric validation studies.
Collapse
Affiliation(s)
- Neha Durgam
- ICON plc, 4130 Parklake Ave Suite 400, Raleigh, NC, 27612, USA
| | | | - Olga Moshkovich
- ICON plc, 4130 Parklake Ave Suite 400, Raleigh, NC, 27612, USA
| | - Ali Rezaie
- Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | | | | | - James Stansbury
- ICON plc, 4130 Parklake Ave Suite 400, Raleigh, NC, 27612, USA
| | | |
Collapse
|
46
|
Chen MM, Wang P, Xie XH, Nie Z, Xu SX, Zhang N, Wang W, Yao L, Liu Z. Young adults with major depression show altered microbiome. Neuroscience 2023; 522:23-32. [PMID: 37169166 DOI: 10.1016/j.neuroscience.2023.05.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 04/26/2023] [Accepted: 05/02/2023] [Indexed: 05/13/2023]
Abstract
There is growing basic and clinical evidence that major depressive disorder (MDD) is associated with gut microbiome alterations, but clinical studies have tended not to adjust for confounding factors. And few studies on the gut microbiome focused on young adults with MDD. Here we performed a pilot study to compare the gut microbiome of young adults with MDD with healthy controls. Shotgun metagenomic sequencing was performed on stool samples obtained from 40 young adults with MDD and 42 healthy controls. After controlling for confounding factors including sex, age, BMI, alcohol or cigarette consumption, bowel movement quality, exercise or defecation frequency, we compared microbiome diversity between groups, identified differentially abundant taxa, and further compared functional differences through gut-brain and gut-metabolic module analysis. There were no significant differences in overall gut microbiome structure and function in young adults with MDD compared with controls. Abundance of Sutterellaceae and species belonging to Clostridium, Eubacterium, and Ruminococcus were significantly different between groups. The cysteine degradation I pathway was increased in MDD. After controlling for most confounding factors, this pilot study provides new evidence on the specific, often subtle gut dysbiosis affecting young adults with depression.
Collapse
Affiliation(s)
- Mian-Mian Chen
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000 China
| | - Peilin Wang
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000 China
| | - Xin-Hui Xie
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000 China
| | - Zhaowen Nie
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000 China
| | - Shu-Xian Xu
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000 China
| | - Nan Zhang
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000 China
| | - Wei Wang
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000 China
| | - Lihua Yao
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000 China
| | - Zhongchun Liu
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000 China.
| |
Collapse
|
47
|
Grahnemo L, Nethander M, Coward E, Gabrielsen ME, Sree S, Billod JM, Sjögren K, Engstrand L, Dekkers KF, Fall T, Langhammer A, Hveem K, Ohlsson C. Identification of three bacterial species associated with increased appendicular lean mass: the HUNT study. Nat Commun 2023; 14:2250. [PMID: 37080991 PMCID: PMC10119287 DOI: 10.1038/s41467-023-37978-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Accepted: 04/05/2023] [Indexed: 04/22/2023] Open
Abstract
Appendicular lean mass (ALM) associates with mobility and bone mineral density (BMD). While associations between gut microbiota composition and ALM have been reported, previous studies rely on relatively small sample sizes. Here, we determine the associations between prevalent gut microbes and ALM in large discovery and replication cohorts with information on relevant confounders within the population-based Norwegian HUNT cohort (n = 5196, including women and men). We show that the presence of three bacterial species - Coprococcus comes, Dorea longicatena, and Eubacterium ventriosum - are reproducibly associated with higher ALM. When combined into an anabolic species count, participants with all three anabolic species have 0.80 kg higher ALM than those without any. In an exploratory analysis, the anabolic species count is positively associated with femoral neck and total hip BMD. We conclude that the anabolic species count may be used as a marker of ALM and BMD. The therapeutic potential of these anabolic species to prevent sarcopenia and osteoporosis needs to be determined.
Collapse
Affiliation(s)
- Louise Grahnemo
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
| | - Maria Nethander
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Eivind Coward
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
| | - Maiken Elvestad Gabrielsen
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
| | - Satya Sree
- Bio-Me, Oslo Science Park, Gaustadalléen 21, N-0349, Oslo, Norway
| | - Jean-Marc Billod
- Bio-Me, Oslo Science Park, Gaustadalléen 21, N-0349, Oslo, Norway
| | - Klara Sjögren
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lars Engstrand
- Department of Microbiology, Tumor and Cell Biology, Centre for Translational Microbiome Research, Karolinska Institutet, Karolinska Hospital, Biomedicum A8, Solnavägen 9, 171 65, Stockholm, Sweden
| | - Koen F Dekkers
- Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | - Tove Fall
- Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | - Arnulf Langhammer
- HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway
- Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
| | - Kristian Hveem
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
- HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway
- Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
| | - Claes Ohlsson
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Region Västra Götaland, Sahlgrenska University Hospital, Department of Drug Treatment, Gothenburg, Sweden
| |
Collapse
|
48
|
Breier A, Brannan SK, Paul SM, Miller AC. Evidence of trospium's ability to mitigate cholinergic adverse events related to xanomeline: phase 1 study results. Psychopharmacology (Berl) 2023; 240:1191-1198. [PMID: 37036495 PMCID: PMC10102054 DOI: 10.1007/s00213-023-06362-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 03/29/2023] [Indexed: 04/11/2023]
Abstract
RATIONALE The M1/M4 preferring muscarinic receptor agonist xanomeline demonstrated antipsychotic and procognitive effects in patients with Alzheimer's disease or schizophrenia in prior studies, but further clinical development was limited by cholinergic adverse events (AEs). KarXT combines xanomeline with the peripherally restricted muscarinic receptor antagonist trospium with the goal of improving tolerability and is in clinical development for schizophrenia and other neuropsychiatric disorders. OBJECTIVE Test the hypothesis that trospium can mitigate cholinergic AEs associated with xanomeline. METHODS Healthy volunteers enrolled in this phase 1 (NCT02831231), single-site, 9-day, double-blind comparison of xanomeline alone (n = 33) versus KarXT (n = 35). Rates of five prespecified cholinergic AEs (nausea, vomiting, diarrhea, excessive sweating, salivary hypersecretion) were compared between treatment arms. Vital signs, electrocardiograms (ECGs), safety laboratory values, and pharmacokinetic (PK) analyses were assessed. A self-administered visual analog scale (VAS) and clinician-administered scales were employed. RESULTS Compared with xanomeline alone, KarXT reduced composite incidences of the five a priori selected cholinergic AEs by 46% and each individual AE by ≥ 29%. There were no episodes of syncope in KarXT-treated subjects; two cases occurred in the xanomeline-alone arm. The rate of postural dizziness was 11.4% in the KarXT arm versus 27.2% with xanomeline alone. ECG, vital signs, and laboratory values were not meaningfully different between treatment arms. The VAS and clinician-administered scales tended to favor KarXT. PK analysis revealed that trospium did not affect xanomeline's PK profile. CONCLUSIONS Trospium was effective in mitigating xanomeline-related cholinergic AEs. KarXT had an improved safety profile compared with xanomeline alone.
Collapse
Affiliation(s)
- Alan Breier
- Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA
- Karuna Therapeutics, Boston, MA, USA
| | | | | | | |
Collapse
|
49
|
Kaplan AI, Mazor Y, Prott GM, Sequeira C, Jones MP, Malcolm A. Experiencing multiple concurrent functional gastrointestinal disorders is associated with greater symptom severity and worse quality of life in chronic constipation and defecation disorders. Neurogastroenterol Motil 2023; 35:e14524. [PMID: 36578247 DOI: 10.1111/nmo.14524] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 10/18/2022] [Accepted: 12/12/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND Recent community-based studies have demonstrated that experiencing multiple concurrent functional gastrointestinal disorders (FGIDs) is associated with increased somatization, worse quality of life (QoL), and greater health care utilization. However, the presence of multiple overlapping FGIDs is unstudied specifically in chronic constipation and functional defecation disorders (FDD). We investigated the prevalence and impact of additional nonconstipation FGIDs on constipation severity, anorectal physiology, anxiety and depression, and QoL, in patients with chronic constipation and FDD. METHODS One-hundred and forty-six consecutive patients with functional constipation or irritable bowel syndrome (IBS-C/IBS-M) presenting to a tertiary referral Neurogastroenterology Clinic were studied. In addition, 90/146 (62%) qualified for FDD due to abnormal defecatory physiology. Patients underwent comprehensive baseline assessment comprising anorectal physiology, Bristol Stool Chart, Rome questionnaire, Knowles-Eccersley-Scott-Symptom (KESS) constipation score, Hospital Anxiety, and Depression Scale, and modified 36-Item Short Form Health Survey (SF-36) for QoL. Additional FGIDs were diagnosed using Rome III criteria. KEY RESULTS Additional nonconstipation FGIDs occurred in 85% of patients, with a mean of 2.1 (SD 1.6) additional FGIDs. Patients with four or more additional FGIDs experienced greater constipation severity compared to those with no additional FGIDs (p = 0.004). Comorbid FGIDs were associated with worse SF-36 scores for physical functioning (p < 0.001), role-physical (p = 0.005), bodily pain (p < 0.001), vitality (p = 0.008), social functioning (p = 0.004), and mental health index (p = 0.031). CONCLUSIONS AND INFERENCES Functional gastrointestinal disorders comorbidity is highly prevalent in chronic constipation and defecatory disorders, and this is associated with greater symptom severity and worse QoL. Multimodal treatments targeting comorbid FGIDs may lead to superior outcomes.
Collapse
Affiliation(s)
- Adam I Kaplan
- Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
- Neurogastroenterology Unit, Department of Gastroenterology, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Yoav Mazor
- Neurogastroenterology Unit, Department of Gastroenterology, Rambam Health Care Campus, Haifa, Israel
- Department of Medical Neurobiology, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Gillian M Prott
- Neurogastroenterology Unit, Department of Gastroenterology, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Carol Sequeira
- Neurogastroenterology Unit, Department of Gastroenterology, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Michael P Jones
- Deputy Head of Psychology Department, School of Psychological Sciences, Macquarie University, Sydney, New South Wales, Australia
| | - Allison Malcolm
- Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
- Neurogastroenterology Unit, Department of Gastroenterology, Royal North Shore Hospital, Sydney, New South Wales, Australia
| |
Collapse
|
50
|
Gai Z, Dong Y, Xu F, Zhang J, Yang Y, Wang Y. Changes in the gut microbiota composition of healthy young volunteers after administration of Lacticaseibacillus rhamnosus LRa05: A placebo-controlled study. Front Nutr 2023; 10:1105694. [PMID: 36998912 PMCID: PMC10043436 DOI: 10.3389/fnut.2023.1105694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Accepted: 02/27/2023] [Indexed: 03/16/2023] Open
Abstract
The gut microbiota promotes gastrointestinal health in humans; however, the effect of probiotics on the gut microbiota of healthy adults has not been documented clearly. This placebo-controlled study was conducted to assess the effect of Lacticaseibacillus rhamnosus LRa05 supplementation on the gut microbiota of healthy adults. The subjects (N = 100) were randomized 1:1 to receive (1) maltodextrin (placebo, CTL group) and (2) maltodextrin + strain LRa05 (1 × 1010 colony-forming units/day, LRa05 group). The duration of the intervention was 4 weeks, and changes in the gut microbiota from before to after the intervention were investigated using 16S rRNA high-throughput sequencing. In terms of alpha diversity, no significant difference in the composition of the gut microbiota was found between the LRa05 and CTL groups. 16S rRNA sequencing analysis showed that the relative abundance of Lacticaseibacillus significantly increased after supplementation with LRa05. Furthermore, a decreasing trend in the abundance of Sellimonas and a significant decrease in the salmonella infection pathway were observed in the LRa05 group compared with the CTL group. These findings indicate the potential of LRa05 to colonize the human gut and reduce the abundance of harmful bacteria in the microbiota.
Collapse
Affiliation(s)
- Zhonghui Gai
- Department of Research and Development, Wecare-Bio Probiotics (Suzhou) Co., Ltd., Suzhou, China
| | - Yao Dong
- Department of Research and Development, Wecare-Bio Probiotics (Suzhou) Co., Ltd., Suzhou, China
| | - Fei Xu
- College of Food Science and Technology, Henan University of Technology, Zhengzhou, China
- Henan Province Wheat-Flour Staple Food Engineering Technology Research Centre, Zhengzhou, China
- *Correspondence: Fei Xu,
| | - Junli Zhang
- Department of Research and Development, Wecare-Bio Probiotics (Suzhou) Co., Ltd., Suzhou, China
| | - Yujiao Yang
- College of Food Science and Technology, Henan University of Technology, Zhengzhou, China
- Henan Province Wheat-Flour Staple Food Engineering Technology Research Centre, Zhengzhou, China
| | - Yuwen Wang
- College of Food Science and Technology, Henan University of Technology, Zhengzhou, China
- Henan Province Wheat-Flour Staple Food Engineering Technology Research Centre, Zhengzhou, China
| |
Collapse
|