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Feng X, Hu J, Zhang X. Prevalence and predictors of small intestinal bacterial overgrowth in inflammatory bowel disease: a meta-analysis. Front Med (Lausanne) 2025; 11:1490506. [PMID: 39906350 PMCID: PMC11792544 DOI: 10.3389/fmed.2024.1490506] [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: 09/03/2024] [Accepted: 12/11/2024] [Indexed: 02/06/2025] Open
Abstract
Background Small intestinal bacterial overgrowth (SIBO) has been reported to be very common among individuals with inflammatory bowel disease (IBD), and the prevalence of SIBO is highly variable. We conducted this study to calculate the prevalence and identify predictors of SIBO in IBD. Methods PubMed, Cochrane Library, and EMBASE from inception to March 2024 were searched for studies evaluating the prevalence of SIBO in IBD. We calculated the pooled prevalence of SIBO among IBD patients and the odds ratio (OR) of SIBO in IBD compared with healthy controls. Besides, we also evaluated predictors of SIBO in IBD patients. Results Twenty-nine studies (3,250 IBD, 708 controls) were included in our study. The pooled prevalence of SIBO in IBD was 31.0% (95% CI 25.2-37.1), and the prevalence of SIBO was higher in IBD compared with healthy controls (OR 5.25, 95% CI 2.96-9.32). The pooled prevalence of SIBO was higher among CD patients (32.2, 95% CI 25.9-38.8) compared with UC patients (27.8, 95% CI 18.5-38.1). The odds of lower BMI (mean difference = -1.04; 95% CI -1.86 to -0.23), bloating (OR = 3.02, 95% CI 1.22-7.5), flatulence (OR = 4.70, 95% CI 1.44-15.35), history of abdominal surgery (OR = 2.05, 95% CI 1.35-3.11), and stricturing/penetrating disease behavior (OR = 3.51, 95% CI 1.67-7.40) increased significantly in IBD patients with SIBO compared to those without SIBO. Antibiotic treatment may be effective for SIBO in IBD patients. Conclusion Nearly one-third of IBD patients present with SIBO positive, and the odds of SIBO in IBD was increased by 5.25-fold compared with healthy controls. Lower BMI, bloating, flatulence, history of abdominal surgery, and stricturing/penetrating disease behavior were predictors of SIBO in IBD patients.
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Affiliation(s)
- Xin Feng
- Department of Gastroenterology, The People’s Hospital of Yubei District of Chongqing City, Chongqing, China
| | - Jie Hu
- Department of Ultrasound, The People’s Hospital of Yubei District of Chongqing City, Chongqing, China
| | - Xin Zhang
- Department of Gastroenterology, The People’s Hospital of Yubei District of Chongqing City, Chongqing, China
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2
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Mareș CR, Săsăran MO, Mărginean CO. Small Intestinal Bacterial Overgrowth and Childhood Malnutrition: A Comprehensive Review of Available Evidence. Nutrients 2024; 16:4319. [PMID: 39770940 PMCID: PMC11679674 DOI: 10.3390/nu16244319] [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: 11/10/2024] [Revised: 12/04/2024] [Accepted: 12/12/2024] [Indexed: 01/11/2025] Open
Abstract
The gut microbiome is essential for children's normal growth and development, with its formation aligning closely with key stages of growth. Factors like birth method, feeding practices, and antibiotic exposure significantly shape the composition and functionality of the infant gut microbiome. Small intestinal bacterial overgrowth (SIBO) involves an abnormal increase in bacteria within the small intestine. This overgrowth can interfere with digestion, impair nutrient absorption, and lead to both local and systemic inflammation, potentially contributing to malnutrition. In this review, we provide a comprehensive overview of the current understanding of the relationship between SIBO and malnutrition, with a particular focus on the pediatric population. SIBO seems to play an important role in nutrient malabsorption through the gut microbiome imbalance, local inflammation, and disruption of the mucosal intestinal barrier. Additionally, SIBO is more prevalent in digestive disorders linked to malabsorption and malnutrition. Different therapeutic strategies for addressing malnutrition-related SIBO have been proposed. While antibiotics are the primary treatment for SIBO, their effectiveness in promoting weight gain among malnourished children remains uncertain. Hence, future research directed at the impact of microbiome imbalance on nutrient intake and absorption could bring to light new strategies for the effective prevention and treatment of malnutrition.
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Affiliation(s)
- Cristina Roxana Mareș
- Department of Pediatrics 1, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Gheorghe Marinescu Street no 38, 540136 Târgu Mureș, Romania; (C.R.M.); (C.O.M.)
| | - Maria Oana Săsăran
- Department of Pediatrics 3, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Gheorghe Marinescu Street no 38, 540136 Târgu Mureș, Romania
| | - Cristina Oana Mărginean
- Department of Pediatrics 1, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Gheorghe Marinescu Street no 38, 540136 Târgu Mureș, Romania; (C.R.M.); (C.O.M.)
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3
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Klemm N, Moosavi S. Chronic Abdominal Pain in Patients with Inflammatory Bowel Disease in Remission: A Continuing Challenge for Clinicians. Dig Dis Sci 2024; 69:4336-4346. [PMID: 39537891 DOI: 10.1007/s10620-024-08716-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: 06/06/2024] [Accepted: 10/23/2024] [Indexed: 11/16/2024]
Abstract
Inflammatory bowel disease (IBD) is a chronic condition that includes ulcerative colitis and Crohn's disease. It is characterized by a relapsing and remitting pattern that negatively impacts quality of life (QoL). Current goals of treatment involve symptomatic, biochemical, and endoscopic remission in a treat-to-target approach. Despite effective treatment and remission of IBD, many patients report frequent and isolated abdominal pain. A wide range of etiologies exist, including surgery-related, infections, pelvic conditions, immune-related, and systemic illnesses. Disorders of the gut-brain interaction (DGBI), frequently characterized by abdominal pain, are increasingly recognized in IBD patients, including those with quiescent disease. Various mechanisms are involved and numerous non-pharmacologic and pharmacologic therapies have been proposed. Hereby, we outline the pertinent findings of the literature on management of chronic abdominal pain, focusing on quiescent IBD.
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Affiliation(s)
- Natasha Klemm
- Department of Gastroenterology, University of British Columbia, Vancouver, V5Z 1M9, Canada.
| | - Sarvee Moosavi
- Neurogastroenterology & GI Motility, Department of Gastroenterology, University of British Columbia, Vancouver, Canada
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Bayoumy AB, Derijks LJJ, Oldenburg B, de Boer NKH. The Use of Tissue Concentrations of Biological and Small-Molecule Therapies in Clinical Studies of Inflammatory Bowel Diseases. Pharmaceutics 2024; 16:1497. [PMID: 39771479 PMCID: PMC11676153 DOI: 10.3390/pharmaceutics16121497] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 11/15/2024] [Accepted: 11/19/2024] [Indexed: 01/11/2025] Open
Abstract
The introduction of biological therapies has revolutionized inflammatory bowel disease (IBD) management. A critical consideration in developing these therapies is ensuring adequate drug concentrations at the site of action. While blood-based biomarkers have shown limited utility in optimizing treatment (except for TNF-alpha inhibitors and thiopurines), tissue drug concentrations may offer valuable insights. In antimicrobial therapies, tissue concentration monitoring is standard practice and could provide a new avenue for understanding the pharmacokinetics of biological and small-molecule therapies in IBD. Various methods exist for measuring tissue concentrations, including whole tissue sampling, MALDI-MSI, microdialysis, and fluorescent labeling. These techniques offer unique advantages, such as spatial drug-distribution mapping, continuous sampling, or cellular-level analysis. However, challenges remain, including sampling invasiveness, heterogeneity in tissue compartments, and a lack of standardized bioanalytical guidelines. Drug pharmacokinetics are influenced by multiple factors, including molecular properties, disease-induced changes in the gastrointestinal tract, and the timing of sample collection. For example, drug permeability, solubility, and interaction with transporters may vary between Crohn's disease and ulcerative colitis. Research into the tissue concentrations of drugs like anti-TNF agents, ustekinumab, vedolizumab, and tofacitinib has shown variable correlations with clinical outcomes, suggesting potential roles for tissue concentration monitoring in therapeutic drug management. Although routine clinical application is not yet established, exploring tissue drug concentrations may enhance understanding of IBD pharmacotherapy.
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Affiliation(s)
- Ahmed B. Bayoumy
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands;
- Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, 1105 AZ Amsterdam, The Netherlands
| | - Luc J. J. Derijks
- Department of Clinical Pharmacy & Pharmacology, Máxima Medical Centre, 5631 BM Eindhoven, The Netherlands
- Department of Clinical Pharmacy & Toxicology and NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, 6229 HX Maastricht, The Netherlands
| | - Bas Oldenburg
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
| | - Nanne K. H. de Boer
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands;
- Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, 1105 AZ Amsterdam, The Netherlands
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5
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Wielgosz-Grochowska JP, Domanski N, Drywień ME. Identification of SIBO Subtypes along with Nutritional Status and Diet as Key Elements of SIBO Therapy. Int J Mol Sci 2024; 25:7341. [PMID: 39000446 PMCID: PMC11242202 DOI: 10.3390/ijms25137341] [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: 05/23/2024] [Revised: 06/28/2024] [Accepted: 07/01/2024] [Indexed: 07/16/2024] Open
Abstract
Small intestinal bacterial overgrowth (SIBO) is a pathology of the small intestine and may predispose individuals to various nutritional deficiencies. Little is known about whether specific subtypes of SIBO, such as the hydrogen-dominant (H+), methane-dominant (M+), or hydrogen/methane-dominant (H+/M+), impact nutritional status and dietary intake in SIBO patients. The aim of this study was to investigate possible correlations between biochemical parameters, dietary nutrient intake, and distinct SIBO subtypes. This observational study included 67 patients who were newly diagnosed with SIBO. Biochemical parameters and diet were studied utilizing laboratory tests and food records, respectively. The H+/M+ group was associated with low serum vitamin D (p < 0.001), low serum ferritin (p = 0.001) and low fiber intake (p = 0.001). The M+ group was correlated with high serum folic acid (p = 0.002) and low intakes of fiber (p = 0.001) and lactose (p = 0.002). The H+ group was associated with low lactose intake (p = 0.027). These results suggest that the subtype of SIBO may have varying effects on dietary intake, leading to a range of biochemical deficiencies. Conversely, specific dietary patterns may predispose one to the development of a SIBO subtype. The assessment of nutritional status and diet, along with the diagnosis of SIBO subtypes, are believed to be key components of SIBO therapy.
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Affiliation(s)
| | - Nicole Domanski
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada;
| | - Małgorzata Ewa Drywień
- Department of Human Nutrition, Institute of Human Nutrition Sciences, Warsaw University of Life Sciences, 02-776 Warsaw, Poland;
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Zhang X, Zhang X, Yang Y. Update of gut gas metabolism in ulcerative colitis. Expert Rev Gastroenterol Hepatol 2024; 18:339-349. [PMID: 39031456 DOI: 10.1080/17474124.2024.2383635] [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: 12/11/2023] [Accepted: 07/19/2024] [Indexed: 07/22/2024]
Abstract
INTRODUCTION Ulcerative colitis (UC) is a chronic, nonspecific inflammatory disease of the intestine. The intestinal microbiota is essential in the occurrence and development of UC. Gut gases are produced via bacterial fermentation or chemical interactions, which can reveal altered intestinal microbiota, abnormal cellular metabolism, and inflammation responses. Recent studies have demonstrated that UC patients have an altered gut gas metabolism. AREAS COVERED In this review, we integrate gut gas metabolism advances in UC and discuss intestinal gases' clinical values as new biomarkers or therapeutic targets for UC, providing the foundation for further research. Literature regarding gut gas metabolism and its significance in UC from inception to October 2023 was searched on the MEDLINE database and references from relevant articles were investigated. EXPERT OPINION Depending on their type, concentration, and volume, gut gases can induce or alleviate clinical symptoms and regulate intestinal motility, inflammatory responses, immune function, and oxidative stress, significantly impacting UC. Gut gases may function as new biomarkers and provide potential diagnostic or therapeutic targets for UC.
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Affiliation(s)
- Xiaohan Zhang
- Medical School, Nankai University, Tianjin, China
- Microbiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Xiuli Zhang
- Microbiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yunsheng Yang
- Microbiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
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Ahmed M, Pu A, Jencks K, Bishu S, Higgins P, Chey WD, Rao K, Lee A. Predictors of irritable bowel syndrome-like symptoms in quiescent inflammatory bowel disease. Neurogastroenterol Motil 2024; 36:e14809. [PMID: 38651743 PMCID: PMC11806413 DOI: 10.1111/nmo.14809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Revised: 04/04/2024] [Accepted: 04/14/2024] [Indexed: 04/25/2024]
Abstract
BACKGROUND Many patients with quiescent inflammatory bowel disease (IBD) suffer from irritable bowel syndrome (IBS)-like symptoms. Although these symptoms cause significant reductions in quality of life, evidence-based treatments are lacking as risk factors and pathophysiology of these symptoms are not clearly defined. We aimed to identify risk factors for development of IBS-like symptoms in IBD patients with quiescent disease. METHODS We performed a single-center retrospective cohort study of adults with IBD from 2015 to 2021. Quiescent IBD was defined by a fecal calprotectin level <250 μg/g of stool or endoscopic evidence of quiescent disease. Cox regression was performed to identify variables that were independently associated with the incident development of IBS-like symptoms in IBD patients. KEY RESULTS A total of 368 IBD patients were included for analysis, including 278 patients with UC and 88 with Crohn's disease. 15.5% of quiescent IBD patients developed IBS symptoms, with an incidence rate of (95% CI 48.0-82.0) 63.3 per 1000 person-years. In the multivariate model, mood disorders (including anxiety and depression) and Crohn's disease were associated with increased risk for developing IBS symptoms. Male sex and higher iron levels conferred lower risk for developing IBS symptoms. Results from the multivariable model were similar in sensitivity analysis with quiescent IBD defined by fecal calprotectin level <150 mcg/g. CONCLUSIONS & INFERENCES Mood disorder and Crohn's disease were positively associated with IBS-like symptoms in quiescent IBD, whereas male sex and iron levels were protective. Our results were robust to different fecal calprotectin levels, arguing against inflammation as a mechanism for IBS-like symptoms. This data suggests noninflammatory mechanisms may be important in the pathogenesis of IBS-like symptoms in quiescent IBD. Future work may address whether modifying these risk factors may alter disease course.
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Affiliation(s)
- Mehwish Ahmed
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Autumn Pu
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Kara Jencks
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Shrinivas Bishu
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Peter Higgins
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - William D. Chey
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Krishna Rao
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
- Division of Infectious Diseases, University of Michigan, Ann Arbor, Michigan, USA
| | - Allen Lee
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
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Aliu A, Bosch DHCA, Keszthelyi D, Rezazadeh Ardabili A, Colombel JF, Sawyer R, Törnblom H, Hart A, Jonkers DMAE, Pierik MJ, Mujagic Z. Review article: A practical approach to persistent gastrointestinal symptoms in inflammatory bowel disease in remission. Aliment Pharmacol Ther 2024; 59:1470-1488. [PMID: 38590140 DOI: 10.1111/apt.17988] [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: 10/16/2023] [Revised: 11/29/2023] [Accepted: 03/25/2024] [Indexed: 04/10/2024]
Abstract
BACKGROUND Persistent gastrointestinal symptoms are prevalent in adult patients with inflammatory bowel disease (IBD), even when endoscopic remission is reached. These symptoms can have profound negative effects on the quality of life of affected patients and can be difficult to treat. They may be caused by IBD-related complications or comorbid disorders, but they can also be explained by irritable bowel syndrome (IBS)-like symptoms. AIMS To provide a practical step-by-step guide to diagnose and treat persistent gastrointestinal symptoms in patients with IBD in remission via a personalised approach. METHODS We scrutinised relevant literature on causes, diagnostics and treatment of persistent gastrointestinal symptoms (abdominal pain or discomfort, bloating, abdominal distension, diarrhoea, constipation and faecal incontinence) in patients with IBD in remission. RESULTS A graphical practical guide for several steps in diagnosing, identifying potential triggers and adequate treatment of persistent gastrointestinal symptoms in IBD in remission is provided based on supporting literature. The first part of this review focuses on the diagnostic and treatment approaches for potential IBD-related complications and comorbidities. The second part describes the approach to IBS-like symptoms in IBD in remission. CONCLUSIONS Persistent gastrointestinal symptoms in IBD in remission can be traced back to potential pathophysiological mechanisms in individual patients and can be treated adequately. For both IBD-related complications and comorbidities and IBS-like symptoms in IBD in remission, pharmacological, dietary, lifestyle or psychological treatments can be effective. A systematic and personalised approach is required to reduce the burden for patients, healthcare systems, and society.
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Affiliation(s)
- Arta Aliu
- Department Gastroenterology and 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, Maastricht, the Netherlands
| | - Daan H C A Bosch
- Department Gastroenterology and 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, Maastricht, the Netherlands
| | - Daniel Keszthelyi
- Department Gastroenterology and 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, Maastricht, the Netherlands
| | - Ashkan Rezazadeh Ardabili
- Department Gastroenterology and 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, Maastricht, the Netherlands
| | - Jean-Frederic Colombel
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Rachel Sawyer
- IBD Patient Advocacy, Founder of the Bottom Line IBD and IBD Women, UK
| | - Hans Törnblom
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Ailsa Hart
- IBD Unit, St Mark's Hospital & Imperial College, London, UK
| | - Daisy M A E Jonkers
- Department Gastroenterology and 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, Maastricht, the Netherlands
| | - Marieke J Pierik
- Department Gastroenterology and 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, Maastricht, the Netherlands
| | - Zlatan Mujagic
- Department Gastroenterology and 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, Maastricht, the Netherlands
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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.
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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.
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Roszkowska P, Klimczak E, Ostrycharz E, Rączka A, Wojciechowska-Koszko I, Dybus A, Cheng YH, Yu YH, Mazgaj S, Hukowska-Szematowicz B. Small Intestinal Bacterial Overgrowth (SIBO) and Twelve Groups of Related Diseases-Current State of Knowledge. Biomedicines 2024; 12:1030. [PMID: 38790992 PMCID: PMC11117733 DOI: 10.3390/biomedicines12051030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 05/01/2024] [Accepted: 05/03/2024] [Indexed: 05/26/2024] Open
Abstract
The human gut microbiota creates a complex microbial ecosystem, characterized by its high population density, wide diversity, and complex interactions. Any imbalance of the intestinal microbiome, whether qualitative or quantitative, may have serious consequences for human health, including small intestinal bacterial overgrowth (SIBO). SIBO is defined as an increase in the number of bacteria (103-105 CFU/mL), an alteration in the bacterial composition, or both in the small intestine. The PubMed, Science Direct, Web of Science, EMBASE, and Medline databases were searched for studies on SIBO and related diseases. These diseases were divided into 12 groups: (1) gastrointestinal disorders; (2) autoimmune disease; (3) cardiovascular system disease; (4) metabolic disease; (5) endocrine disorders; (6) nephrological disorders; (7) dermatological diseases; (8) neurological diseases (9); developmental disorders; (10) mental disorders; (11) genetic diseases; and (12) gastrointestinal cancer. The purpose of this comprehensive review is to present the current state of knowledge on the relationships between SIBO and these 12 disease groups, taking into account risk factors and the causal context. This review fills the evidence gap on SIBO and presents a biological-medical approach to the problem, clearly showing the groups and diseases having a proven relationship with SIBO, as well as indicating groups within which research should continue to be expanded.
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Affiliation(s)
- Paulina Roszkowska
- Department of Diagnostic Immunology, Pomeranian Medical University, st. Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (P.R.); (I.W.-K.)
| | - Emilia Klimczak
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
| | - Ewa Ostrycharz
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
- Doctoral School, University of Szczecin, st. A. Mickiewicz 16, 71-412 Szczecin, Poland
- Molecular Biology and Biotechnology Center, University of Szczecin, st. Wąska 13, 71-412 Szczecin, Poland
| | - Aleksandra Rączka
- Department of Genetics, West Pomeranian University of Technology, st. Aleja Piastów 45, 70-311 Szczecin, Poland; (A.R.); (A.D.)
| | - Iwona Wojciechowska-Koszko
- Department of Diagnostic Immunology, Pomeranian Medical University, st. Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland; (P.R.); (I.W.-K.)
| | - Andrzej Dybus
- Department of Genetics, West Pomeranian University of Technology, st. Aleja Piastów 45, 70-311 Szczecin, Poland; (A.R.); (A.D.)
| | - Yeong-Hsiang Cheng
- Department of Biotechnology and Animal Science, National Ilan University, Yilan 26047, Taiwan; (Y.-H.C.); (Y.-H.Y.)
| | - Yu-Hsiang Yu
- Department of Biotechnology and Animal Science, National Ilan University, Yilan 26047, Taiwan; (Y.-H.C.); (Y.-H.Y.)
| | - Szymon Mazgaj
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
| | - Beata Hukowska-Szematowicz
- Institute of Biology, University of Szczecin, st. Z. Felczaka 3c, 71-412 Szczecin, Poland; (E.K.); (E.O.); (S.M.)
- Molecular Biology and Biotechnology Center, University of Szczecin, st. Wąska 13, 71-412 Szczecin, Poland
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11
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Cisek AA, Szymańska E, Aleksandrzak-Piekarczyk T, Cukrowska B. The Role of Methanogenic Archaea in Inflammatory Bowel Disease-A Review. J Pers Med 2024; 14:196. [PMID: 38392629 PMCID: PMC10890621 DOI: 10.3390/jpm14020196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 01/28/2024] [Accepted: 02/08/2024] [Indexed: 02/24/2024] Open
Abstract
Methanogenic archaea are a part of the commensal gut microbiota responsible for hydrogen sink and the efficient production of short-chain fatty acids. Dysbiosis of methanogens is suspected to play a role in pathogenesis of variety of diseases, including inflammatory bowel disease (IBD). Unlike bacteria, the diversity of archaea seems to be higher in IBD patients compared to healthy subjects, whereas the prevalence and abundance of gut methanogens declines in IBD, especially in ulcerative colitis. To date, studies focusing on methanogens in pediatric IBD are very limited; nevertheless, the preliminary results provide some evidence that methanogens may be influenced by the chronic inflammatory process in IBD. In this review, we demonstrated the development and diversity of the methanogenic community in IBD, both in adults and children.
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Affiliation(s)
- Agata Anna Cisek
- Department of Pathomorphology, The Children's Memorial Health Institute, Av. Dzieci Polskich 20, 04-730 Warsaw, Poland
| | - Edyta Szymańska
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Av. Dzieci Polskich 20, 04-730 Warsaw, Poland
| | | | - Bożena Cukrowska
- Department of Pathomorphology, The Children's Memorial Health Institute, Av. Dzieci Polskich 20, 04-730 Warsaw, Poland
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12
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Cisek AA, Szymańska E, Wierzbicka-Rucińska A, Aleksandrzak-Piekarczyk T, Cukrowska B. Methanogenic Archaea in the Pediatric Inflammatory Bowel Disease in Relation to Disease Type and Activity. Int J Mol Sci 2024; 25:673. [PMID: 38203843 PMCID: PMC10779203 DOI: 10.3390/ijms25010673] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 12/25/2023] [Accepted: 12/29/2023] [Indexed: 01/12/2024] Open
Abstract
The inflammatory bowel disease (IBD) is associated with gut microbiota dysbiosis; however, studies on methanogens-especially those focused on children-are extremely limited. The aim of this study was to determine the abundance of total methanogenic archaea and their three subgroups: Methanobrevibacter (Mb.) smithii, Methanosphaera (Ms.) stadtmanae, and Methanomassiliicoccales, in the feces of children with both active and inactive Crohn's disease (CD) and ulcerative colitis (UC). The results of a quantitative real-time PCR were cross-referenced with the disease type (CD vs. UC) and activity assessed with the use of Pediatric Crohn's Disease Activity Index (PCDAI) and Pediatric Ulcerative Colitis Activity Index (PUCAI) indices, and fecal calprotectin (FCP) concentration, and compared with controls. There was a significant decrease in the number of total methanogens in CD and UC compared to controls. The prevalence of total methanogens was also lower in UC compared to controls. Furthermore, patients from the inactive UC group were colonized by a lower number of Mb. smithii, and demonstrated the most pronounced positive correlation between the number of Ms. stadtmanae and the FCP concentration. Our results demonstrate that gut methanogens are related to the type and activity of pediatric IBD.
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Affiliation(s)
- Agata Anna Cisek
- Department of Pathomorphology, The Children’s Memorial Health Institute, Av. Dzieci Polskich 20, 04-730 Warsaw, Poland;
| | - Edyta Szymańska
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children’s Memorial Health Institute, Av. Dzieci Polskich 20, 04-730 Warsaw, Poland;
| | - Aldona Wierzbicka-Rucińska
- Department of Biochemistry, Radioimmunology and Experimental Medicine, The Children’s Memorial Health Institute, Av. Dzieci Polskich 20, 04-730 Warsaw, Poland;
| | | | - Bożena Cukrowska
- Department of Pathomorphology, The Children’s Memorial Health Institute, Av. Dzieci Polskich 20, 04-730 Warsaw, Poland;
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13
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Abstract
PURPOSE OF REVIEW This article aims to provide an up-to-date review of small intestinal bacterial overgrowth (SIBO), including etiology and risk factors, clinical manifestations, diagnostic evaluation for suspected SIBO, and therapeutic options. RECENT FINDINGS Recent advances in breath testing, capsule and urine-based testing have opened new avenues and improved diagnostic yield of SIBO. Nonantibiotic-based treatment strategies have shown promising results in initial trials. SUMMARY Small intestinal bacterial overgrowth (SIBO) is a condition defined by the excess bacteria or changes in bacterial composition of the small intestine. These are associated with various gastrointestinal (GI) symptoms such as bloating, abdominal distension, diarrhea, nutrient deficiencies, and even frank weight loss. Small bowel jejunal aspirate of >10 5 CFU/ml has traditionally been considered the gold standard for diagnosis. Glucose and lactulose breath testing have become more common in clinical practice as they are noninvasive, easily accessible, and have lower cost. Treatment focuses on the eradication of excess bacteria in the small bowel and is traditionally done with the use of oral antibiotics. Other emerging therapies may include probiotics, diet manipulation, and prokinetic agents.
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Affiliation(s)
- Hammad Zafar
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Florida, Weston, Florida, USA
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14
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Lim J, Rezaie A. Irritable Bowel Syndrome-Like Symptoms in Quiescent Inflammatory Bowel Disease: A Practical Approach to Diagnosis and Treatment of Organic Causes. Dig Dis Sci 2023; 68:4081-4097. [PMID: 37695549 PMCID: PMC10570178 DOI: 10.1007/s10620-023-08095-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 08/23/2023] [Indexed: 09/12/2023]
Abstract
BACKGROUND Despite achieving remission in inflammatory bowel disease (IBD), persistent gastrointestinal symptoms are common in quiescent IBD. While irritable bowel syndrome (IBS) is commonly diagnosed in IBD, IBS-like symptoms of recurrent abdominal pain and altered bowel habits can also be attributed to a wide range of overlapping gastrointestinal (GI) etiologies and systemic disorders with GI manifestations that often do not respond to conventional IBS therapies. Delay in diagnosis of these conditions can lead to ongoing patient suffering, reduced quality of life, repetition of invasive testing, increased healthcare utilization, and potentially unnecessary empirical escalation of IBD-related treatments. AIMS This review provides a practical approach for the evaluation and diagnosis of IBS mimickers in IBD. We summarize the definition, pathophysiology, diagnosis and treatment of the potential etiologies causing unexplained GI symptoms. CONCLUSION Overlapping conditions can co-exist with IBD and explain IBS-like symptoms. The diagnostic work-up in this population should be individualized and tailored to the predominant symptom pattern, associated clinical signs and symptoms and predisposing conditions that can be obtained from a detailed history and physical examination.
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Affiliation(s)
- Jane Lim
- GI Motility Program, Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai, 8730 Alden Drive, Thalians Bldg, #E203, Los Angeles, CA, 90048, USA.
| | - Ali Rezaie
- GI Motility Program, Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai, 8730 Alden Drive, Thalians Bldg, #E203, Los Angeles, CA, 90048, USA
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15
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Wielgosz-Grochowska JP, Domanski N, Drywień ME. Influence of Body Composition and Specific Anthropometric Parameters on SIBO Type. Nutrients 2023; 15:4035. [PMID: 37764818 PMCID: PMC10535553 DOI: 10.3390/nu15184035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 09/04/2023] [Accepted: 09/16/2023] [Indexed: 09/29/2023] Open
Abstract
Recent observations have shown that Small Intestinal Bacterial Overgrowth (SIBO)affects the host through various mechanisms. While both weight loss and obesity have been reported in the SIBO population due to alterations in the gut microbiome, very little is known about the influence of SIBO type on body composition. This study aimed to evaluate whether there is a link between the three types of SIBO: methane dominant (M+), hydrogen dominant (H+), and methane-hydrogen dominant (H+/M+) and specific anthropometric parameters. This observational study included 67 participants (W = 53, M = 14) with gastrointestinal symptoms and SIBO confirmed by lactulose hydrogen-methane breath tests (LHMBTs) using the QuinTron device. Participants underwent a body composition assessment by Bioelectrical Impedance Analysis (BIA) using the InBody Analyzer. In the H+/M+ group, body weight (p = 0.010), BMI (p = 0.001), body fat in kg (p = 0.009), body fat in % (p = 0.040), visceral fat (p = 0.002), and mineral bone content (p = 0.049) showed an inverse correlation with hydrogen (H2) gas production. These findings suggest that body weight, BMI, body fat, and mineral bone content may be inversely linked to the production of hydrogen and the risk of hydrogen-methane SIBO.
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Affiliation(s)
| | - Nicole Domanski
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada;
| | - Małgorzata Ewa Drywień
- Department of Human Nutrition, Institute of Human Nutrition Sciences, Warsaw University of Life Sciences, 02-776 Warsaw, Poland;
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16
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Parigi TL, D'Amico F, Abreu MT, Dignass A, Dotan I, Magro F, Griffiths AM, Jairath V, Iacucci M, Mantzaris GJ, O'Morain C, Reinisch W, Sachar DB, Turner D, Yamamoto T, Rubin DT, Peyrin-Biroulet L, Ghosh S, Danese S. Difficult-to-treat inflammatory bowel disease: results from an international consensus meeting. Lancet Gastroenterol Hepatol 2023; 8:853-859. [PMID: 37423233 DOI: 10.1016/s2468-1253(23)00154-1] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 05/12/2023] [Accepted: 05/15/2023] [Indexed: 07/11/2023]
Abstract
Many patients with inflammatory bowel disease (IBD) have persistent symptoms and disease activity despite the best available medical or surgical treatments. These patients are commonly referred to as having difficult-to-treat IBD and need additional therapeutic strategies. However, the absence of standard definitions has impeded clinical research efforts and comparisons of data. Under the guidance of the endpoints cluster of the International Organization for the Study of Inflammatory Bowel Disease, we held a consensus meeting to propose a common operative definition for difficult-to-treat IBD. 16 participants from 12 countries voted on 20 statements covering various elements of difficult-to-treat IBD, such as failure of medical and surgical treatments, disease phenotypes, and specific complaints from patients. "Agreement" was defined as at least 75% consensus. The group agreed that difficult-to-treat IBD is defined by the failure of biologics and advanced small molecules with at least two different mechanisms of action, or postoperative recurrence of Crohn's disease after two surgical resections in adults, or one in children. In addition, chronic antibiotic-refractory pouchitis, complex perianal disease, and comorbid psychosocial complications that impair disease management also qualified as difficult-to-treat IBD. Adoption of these criteria could serve to standardise reporting, guide enrolment in clinical trials, and help identify candidates for enhanced treatment strategies.
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Affiliation(s)
- Tommaso Lorenzo Parigi
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy; Faculty of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Ferdinando D'Amico
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Maria T Abreu
- Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Axel Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Goethe-University, Frankfurt, Germany
| | - Iris Dotan
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Fernando Magro
- Unit of Pharmacology and Therapeutics, Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Anne M Griffiths
- Division of Gastroenterology, SickKids Hospital, University of Toronto, Toronto, ON, Canada
| | - Vipul Jairath
- Departments of Medicine, Epidemiology and Biostatistics, Western University, London, ON, Canada
| | - Marietta Iacucci
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland
| | | | - Colm O'Morain
- Department of Gastroenterology, Faculty of Health Sciences, Trinity College Dublin, Dublin, Ireland
| | - Walter Reinisch
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - David B Sachar
- The Dr Henry J Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Dan Turner
- Juliet Keidan Institute of Pediatric Gastroenterology, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
| | | | - David T Rubin
- University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA
| | | | - Subrata Ghosh
- APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy; Faculty of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
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17
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Aslan I, Tarhan Celebi L, Kayhan H, Kizilay E, Gulbahar MY, Kurt H, Cakici B. Probiotic Formulations Containing Fixed and Essential Oils Ameliorates SIBO-Induced Gut Dysbiosis in Rats. Pharmaceuticals (Basel) 2023; 16:1041. [PMID: 37513952 PMCID: PMC10383999 DOI: 10.3390/ph16071041] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 07/13/2023] [Accepted: 07/19/2023] [Indexed: 07/30/2023] Open
Abstract
Dysbiosis of the gut microbiota is associated with the pathogenesis of intestinal diseases such as inflammatory bowel disease, irritable bowel syndrome (IBS), small intestinal bacterial overgrowth (SIBO), and metabolic disease states such as allergies, cardiovascular diseases, obesity, and diabetes. SIBO is a condition characterized by an increased number (>1 × 103 CFU) of abnormal bacterial species in the small intestine. Interest in SIBO has gained importance due to increased awareness of the human microbiome and its potential relationships with human health and disease, which has encouraged new work in this area. In recent years, standard antibiotic regimens (rifaximin and metronidazole) have been used to treat SIBO, but solo antibiotics or their derivatives are insufficient. In this study, the therapeutic effects of the probiotic form, which contains coconut oil and traces of peppermint-lemon-patchouli essential oil, were evaluated on the Dysbiosis-Based Rat SIBO Model. There are significant differences between sick and healthy rats (p = 0.014), between sick rats and rats treated with the oil mix plus probiotic mix protocol (p = 0.026), and between rats treated with only the probiotic and only oil protocols (p = 0.030) in the evaluation of TNF-α levels. Histologically, villi distortion and loss of crypts, epithelial shedding and necrotic changes in the apical regions of the villi, and inflammatory cell infiltrations extending to the lamina propria and submucosa were observed in sick rats. Mitotic figures in villus epithelium and crypts were observed in rats treated with 9.2 × 109 CFU/1000 mg/coconut oil + trace amounts of peppermint-lemon-patchouli essential oil and a probiotic mixture (oil + probiotic mix protocol). A regression of inflammatory reactions and an increase in goblet cells were observed. A decrease was observed in inflammation markers in sick rats. On the other hand, the oil plus probiotic mix protocol recovered digestive system defects in the animals caused by dysbiosis. In the future, these treatment approaches can be effective in the treatment of SIBO.
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Affiliation(s)
- Ismail Aslan
- Department of Pharmaceutical Technology, Hamidiye Faculty of Pharmacy, University of Health Sciences, İstanbul 34668, Turkey
- SFA R&D and Analysis Services, Teknopark İstanbul, İstanbul 34906, Turkey
- ATA BIO Technologies, Teknopol İstanbul, İstanbul 34930, Turkey
| | - Leyla Tarhan Celebi
- SFA R&D and Analysis Services, Teknopark İstanbul, İstanbul 34906, Turkey
- ATA BIO Technologies, Teknopol İstanbul, İstanbul 34930, Turkey
| | - Hulya Kayhan
- Art de Huile, Teknopol İstanbul, İstanbul 34930, Turkey
| | - Emine Kizilay
- Hamidiye Vocational School of Health Services, University of Health Sciences, İstanbul 34668, Turkey
| | - Mustafa Yavuz Gulbahar
- Department of Pathology, Faculty of Veterinary Medicine, Ondokuz Mayıs University, Samsun 55200, Turkey
| | - Halil Kurt
- Department of Medical Biology, Hamidiye International Faculty of Medicine, University of Health Sciences, İstanbul 34668, Turkey
| | - Bekir Cakici
- SFA R&D and Analysis Services, Teknopark İstanbul, İstanbul 34906, Turkey
- ATA BIO Technologies, Teknopol İstanbul, İstanbul 34930, Turkey
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18
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Efremova I, Maslennikov R, Poluektova E, Vasilieva E, Zharikov Y, Suslov A, Letyagina Y, Kozlov E, Levshina A, Ivashkin V. Epidemiology of small intestinal bacterial overgrowth. World J Gastroenterol 2023; 29:3400-3421. [PMID: 37389240 PMCID: PMC10303511 DOI: 10.3748/wjg.v29.i22.3400] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 03/31/2023] [Accepted: 05/11/2023] [Indexed: 06/06/2023] Open
Abstract
Small intestinal bacterial overgrowth (SIBO) is defined as an increase in the bacterial content of the small intestine above normal values. The presence of SIBO is detected in 33.8% of patients with gastroenterological complaints who underwent a breath test, and is significantly associated with smoking, bloating, abdominal pain, and anemia. Proton pump inhibitor therapy is a significant risk factor for SIBO. The risk of SIBO increases with age and does not depend on gender or race. SIBO complicates the course of a number of diseases and may be of pathogenetic significance in the development of their symptoms. SIBO is significantly associated with functional dyspepsia, irritable bowel syndrome, functional abdominal bloating, functional constipation, functional diarrhea, short bowel syndrome, chronic intestinal pseudo-obstruction, lactase deficiency, diverticular and celiac diseases, ulcerative colitis, Crohn’s disease, cirrhosis, metabolic-associated fatty liver disease (MAFLD), primary biliary cholangitis, gastroparesis, pancreatitis, cystic fibrosis, gallstone disease, diabetes, hypothyroidism, hyperlipidemia, acromegaly, multiple sclerosis, autism, Parkinson’s disease, systemic sclerosis, spondylarthropathy, fibromyalgia, asthma, heart failure, and other diseases. The development of SIBO is often associated with a slowdown in orocecal transit time that decreases the normal clearance of bacteria from the small intestine. The slowdown of this transit may be due to motor dysfunction of the intestine in diseases of the gut, autonomic diabetic polyneuropathy, and portal hypertension, or a decrease in the motor-stimulating influence of thyroid hormones. In a number of diseases, including cirrhosis, MAFLD, diabetes, and pancreatitis, an association was found between disease severity and the presence of SIBO. Further work on the effect of SIBO eradication on the condition and prognosis of patients with various diseases is required.
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Affiliation(s)
- Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Ekaterina Vasilieva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Yury Zharikov
- Department of Human Anatomy and Histology, Sechenov University, Moscow 125009, Russia
| | - Andrey Suslov
- Department of Human Anatomy and Histology, Sechenov University, Moscow 125009, Russia
| | - Yana Letyagina
- N.V. Sklifosovsky Institute of Clinical Medicine, Sechenov University, Moscow 119991, Russia
| | - Evgenii Kozlov
- Department of Clinical Immunology and Allergy, Sechenov University, Moscow 119991, Russia
| | - Anna Levshina
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Department of Clinical Immunology and Allergy, Sechenov University, Moscow 119991, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
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19
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Shah A, Ghoshal UC, Holtmann GJ. Unravelling the controversy with small intestinal bacterial overgrowth. Curr Opin Gastroenterol 2023; 39:211-218. [PMID: 37144539 DOI: 10.1097/mog.0000000000000928] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
PURPOSE OF REVIEW The aim of this review is to summarize the current and emergent approaches to characterize the small intestinal microbiota and discuss the treatment options for management of small intestinal bacterial overgrowth (SIBO). RECENT FINDINGS This review captures the growing body of evidence for the role of SIBO, a type of small intestinal dysbiosis in the pathophysiology various gastrointestinal and extraintestinal disorders. We have highlighted the drawbacks of the available methods for characterizing the small intestinal microbiota and focus on the new culture-independent techniques to diagnose SIBO. Although recurrence is common, targeted modulation of the gut microbiome as a therapeutic option for management of SIBO is associated with improvement in symptoms and quality of life. SUMMARY As a first step to precisely characterize the potential link between SIBO and various disorders, we need to address the methodological limitations of the available traditional tests for diagnosing SIBO. There is an urgency to develop culture independent techniques that can be routinely used in clinical setting, that will enable characterization of the gastrointestinal microbiome and explore the response to antimicrobial therapy including the links between long-lasting symptom resolution and the microbiome.
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Affiliation(s)
- Ayesha Shah
- The University of Queensland, Faculty of Medicine and Faculty of Health and Behavioural Sciences
- Princess Alexandra Hospital, Department of Gastroenterology & Hepatology, Brisbane, QLD, Australia
| | - Uday C Ghoshal
- Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Gerald J Holtmann
- The University of Queensland, Faculty of Medicine and Faculty of Health and Behavioural Sciences
- Princess Alexandra Hospital, Department of Gastroenterology & Hepatology, Brisbane, QLD, Australia
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20
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Tansel A, Levinthal DJ. Understanding Our Tests: Hydrogen-Methane Breath Testing to Diagnose Small Intestinal Bacterial Overgrowth. Clin Transl Gastroenterol 2023; 14:e00567. [PMID: 36744854 PMCID: PMC10132719 DOI: 10.14309/ctg.0000000000000567] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 01/26/2023] [Indexed: 02/07/2023] Open
Abstract
There is increasing appreciation that small intestinal bacterial overgrowth (SIBO) drives many common gastrointestinal symptoms, including diarrhea, bloating, and abdominal pain. Breath testing via measurement of exhaled hydrogen and methane gases following ingestion of a readily metabolized carbohydrate has become an important noninvasive testing paradigm to help diagnose SIBO. However, because of a number of physiological and technical considerations, how and when to use breath testing in the diagnosis of SIBO remains a nuanced clinical decision. This narrative review provides a comprehensive overview of breath testing paradigms including the indications for testing, how to administer the test, and how patient factors influence breath testing results. We also explore the performance characteristics of breath testing (sensitivity, specificity, positive and negative predictive values, likelihood ratios, and diagnostic odds ratio). Additionally, we describe complementary and alternative tests for diagnosing SIBO. We discuss applications of breath testing for research. Current estimates of SIBO prevalence among commonly encountered high-risk populations are reviewed to provide pretest probability estimates under a variety of clinical situations. Finally, we discuss how to integrate breath test performance characteristics into clinical care decisions using clinical predictors and the Fagan nomogram.
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Affiliation(s)
- Aylin Tansel
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, USA
| | - David J. Levinthal
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, USA
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21
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Bischoff SC, Bager P, Escher J, Forbes A, Hébuterne X, Hvas CL, Joly F, Klek S, Krznaric Z, Ockenga J, Schneider S, Shamir R, Stardelova K, Bender DV, Wierdsma N, Weimann A. ESPEN guideline on Clinical Nutrition in inflammatory bowel disease. Clin Nutr 2023; 42:352-379. [PMID: 36739756 DOI: 10.1016/j.clnu.2022.12.004] [Citation(s) in RCA: 103] [Impact Index Per Article: 51.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 12/05/2022] [Indexed: 01/15/2023]
Abstract
The present guideline is an update and extension of the ESPEN scientific guideline on Clinical Nutrition in Inflammatory Bowel Disease published first in 2017. The guideline has been rearranged according to the ESPEN practical guideline on Clinical Nutrition in Inflammatory Bowel Disease published in 2020. All recommendations have been checked and, if needed, revised based on new literature, before they underwent the ESPEN consensus procedure. Moreover, a new chapter on microbiota modulation as a new option in IBD treatment has been added. The number of recommendations has been increased to 71 recommendations in the guideline update. The guideline is aimed at professionals working in clinical practice, either in hospitals or in outpatient medicine, and treating patients with IBD. General aspects of care in patients with IBD, and specific aspects during active disease and in remission are addressed. All recommendations are equipped with evidence grades, consensus rates, short commentaries and links to cited literature.
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Affiliation(s)
- Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Palle Bager
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
| | - Johanna Escher
- Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
| | - Alastair Forbes
- Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
| | - Xavier Hébuterne
- Department of Gastroenterology and Clinical Nutrition, CHU of Nice, University Côte d'Azur, Nice, France.
| | - Christian Lodberg Hvas
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
| | - Francisca Joly
- Department of Gastroenterology and Nutrition Support, CHU de Beaujon, APHP, University of Paris, Paris, France.
| | - Stansilaw Klek
- Surgical Oncology Clinic, Maria Sklodowska-Curie National Cancer Institute, Krakow, Poland.
| | - Zeljko Krznaric
- Department of Gastroenterology, Hepatology and Nutrition, University Hospital Centre Zagreb, University of Zagreb, Croatia.
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen-Mitte, Bremen FRG, Bremen, Germany.
| | - Stéphane Schneider
- Department of Gastroenterology and Clinical Nutrition, CHU de Nice, University Côte d'Azur, Nice, France.
| | - Raanan Shamir
- Institute for Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Kalina Stardelova
- University Clinic for Gastroenterohepatology, Clinical Campus "Mother Theresa", University St Cyrul and Methodius, Skopje, North Macedonia.
| | - Darija Vranesic Bender
- Unit of Clinical Nutrition, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
| | - Nicolette Wierdsma
- Department of Nutrition and Dietetics, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
| | - Arved Weimann
- Department of General, Visceral and Oncological Surgery, St. George Hospital, Leipzig, Germany.
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22
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Wei H, Yuan Z, Ren K, Jin Y, Ren L, Cao B, Zhou Y, Chen L. Body Composition in Inflammatory Bowel Disease. ARCHIVES OF IRANIAN MEDICINE 2023; 26:172-175. [PMID: 37543940 PMCID: PMC10685726 DOI: 10.34172/aim.2023.26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 02/25/2023] [Indexed: 08/08/2023]
Abstract
Inflammatory bowel disease (IBD) is associated with body composition changes, which are associated with clinical prognosis, response to therapy, and quality of life in IBD patients. Therefore, it is critical to review the body composition distribution in IBD, summarize the potential factors affecting body composition distribution, and take steps to improve the body composition distribution of IBD patients as early as possible. In the current review, we searched PubMed via keywords 'inflammatory bowel disease', or 'IBD', or 'Crohn's disease', or 'CD', or 'ulcerative colitis', or 'UC', and 'body composition'. Malnutrition and sarcopenia are common in IBD patients and are associated with the clinical course, prognosis, and need for surgery. Disease activity, reduced nutrition intake, vitamin D deficiency, and intestinal dysbiosis are factors contributing to changed body composition. Early use of biological agents to induce remission is critical to improving body composition distribution in IBD patients, supplementation of vitamin D is also important, and moderate physical activity is recommended in IBD patients with clinical remission.
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Affiliation(s)
- Hongyun Wei
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - Ziying Yuan
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - Keyu Ren
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - Yanchun Jin
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - Linlin Ren
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - Bin Cao
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China
| | - Yuanyuan Zhou
- The Fourth Department of the Digestive Disease Center, Suining Central Hospital, Suining, Sichuan 629000, P.R. China
| | - Linlin Chen
- The Fourth Department of the Digestive Disease Center, Suining Central Hospital, Suining, Sichuan 629000, P.R. China
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23
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Impact of Small Intestinal Bacterial Overgrowth in Patients with Inflammatory Bowel Disease and Other Gastrointestinal Disorders-A Retrospective Analysis in a Tertiary Single Center and Review of the Literature. J Clin Med 2023; 12:jcm12030935. [PMID: 36769583 PMCID: PMC9917804 DOI: 10.3390/jcm12030935] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 01/20/2023] [Accepted: 01/22/2023] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Small intestinal bacterial overgrowth (SIBO) is often found in patients with gut dysbiosis such as irritable bowel syndrome. Recently, the association of SIBO and inflammatory bowel disease (IBD) has been described in some cases. While clinical symptoms might be similar in IBD and SIBO, treatment is quite different for both diseases. Therefore, the differentiation between SIBO or a flare in IBD patients is key to optimizing treatment for these patients. METHODS We retrospectively investigated our patients with IBD receiving a glucose breath test for SIBO and correlated the results with the clinical symptoms (clinical remission or active disease). RESULTS 128 patients with the diagnosis "colitis" were analyzed in our cohort. Fifty-three (41.4%) patients had Crohn's disease and 22 (17.2%) patients were suffering from ulcerative colitis. Seventy-four (57.8%) were female and 54 (42.2%) were male patients. A total of 18 (14.1%) patients had a positive testing for SIBO. Eleven (61.1%) cases were associated with CD patients and two (11.1%) with UC. IBD patients in clinical remission had a positive SIBO in six (19.4%) cases, while IBD patients with active disease were positive in nine (15.3%) cases. The proportion of positive SIBO in active IBD patients was higher; however, it did not reach significance. Older age was a risk factor for SIBO in patients with CD (p < 0.003). CONCLUSIONS In our study, we could show that an increased amount of SIBO was found in IBD patients and was especially more frequent in patients with CD than in those with UC. In UC patients, SIBO rates were not different to patients with other gastrointestinal diseases investigated (e.g., infectious colitis, collagenous colitis, or irritable bowel syndrome). In active IBD, positive SIBO was detected more often numerically compared to quiescent disease; however, due to the low number of patients included, it was not significant. However, older age was a significant risk factor for SIBO in patients with CD. SIBO is of clinical relevance in the vulnerable patient cohort with IBD, and its real prevalence and impact needs to be investigated in further and larger clinical trials.
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24
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Wu EH, Guo Z, Zhu WM. Postoperative diarrhea in Crohn’s disease: Pathogenesis, diagnosis, and therapy. World J Clin Cases 2023; 11:7-16. [PMID: 36687182 PMCID: PMC9846968 DOI: 10.12998/wjcc.v11.i1.7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Revised: 12/08/2022] [Accepted: 12/23/2022] [Indexed: 01/04/2023] Open
Abstract
Diarrhea is a frequent symptom in postoperative patients with Crohn’s diseases (CD), and several different mechanisms likely account for postoperative diarrhea in CD. A targeted strategy based on a comprehensive understanding of postoperative diarrhea is helpful for better postoperative recovery.
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Affiliation(s)
- En-Hao Wu
- Department of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
| | - Zhen Guo
- Department of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
| | - Wei-Ming Zhu
- Department of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
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25
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Guo H, Lu S, Zhang J, Chen C, Du Y, Wang K, Duan L. Berberine and rifaximin effects on small intestinal bacterial overgrowth: Study protocol for an investigator-initiated, double-arm, open-label, randomized clinical trial (BRIEF-SIBO study). Front Pharmacol 2023; 14:1121435. [PMID: 36873985 PMCID: PMC9974661 DOI: 10.3389/fphar.2023.1121435] [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: 12/11/2022] [Accepted: 01/31/2023] [Indexed: 02/17/2023] Open
Abstract
Introduction: Small intestinal bacterial overgrowth (SIBO) leads to non-specific abdominal discomfort and nutrient malabsorption. Currently, rifaximin is widely applied in SIBO based on its antibacterial and non-absorbable nature. Berberine is a natural component of many popular medicine plants that ameliorates intestinal inflammation in humans through its modification of the gut microbiota. Potential effect of berberine to the gut may provide therapeutic target for SIBO. We aimed to evaluate the effect of berberine compared with rifaximin on SIBO patients. Methods: This is an investigator-initiated, single-center, open-label, double-arm randomized controlled trial, termed BRIEF-SIBO (Berberine and rifaximin effects for small intestinal bacterial overgrowth). In total, 180 patients will be recruited and allocated to an intervention group (berberine) and a control group (rifaximin). Each participant will receive one 400 mg drug twice a day (800 mg daily) for 2 weeks. The total follow-up period is 6 weeks from the start of medication. The primary outcome is a negative breath test. The secondary outcomes include abdominal symptom relief and alteration in gut microbiota. Efficacy assessment will be performed every 2 weeks, as well as safety assessment during the treatment. The primary hypothesis is that berberine is not inferior to rifaximin for SIBO. Discussion: The BRIEF-SIBO study is the first clinical trial assessing the eradication effects of 2 weeks of berberine treatment in SIBO patients. The effect of berberine will be fully verified by using rifaximin as the positive control. The findings of this study may have implications for the management of SIBO, especially increasing the awareness of both physicians and patients who are suffering from long-term abdominal discomfort and avoiding excessive examination.
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Affiliation(s)
- Huaizhu Guo
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Siqi Lu
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Jindong Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Chen Chen
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Yanlin Du
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Kun Wang
- 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
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26
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Brown G, Hoedt EC, Keely S, Shah A, Walker MM, Holtmann G, Talley NJ. Role of the duodenal microbiota in functional dyspepsia. Neurogastroenterol Motil 2022; 34:e14372. [PMID: 35403776 PMCID: PMC9786680 DOI: 10.1111/nmo.14372] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 02/04/2022] [Accepted: 03/14/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND Functional dyspepsia (FD) is a common and debilitating gastrointestinal disorder attributed to altered gut-brain interactions. While the etiology of FD remains unknown, emerging research suggests the mechanisms are likely multifactorial and heterogenous among patient subgroups. Small bowel motor disturbances, visceral hypersensitivity, chronic microinflammation, and increased intestinal tract permeability have all been linked to the pathogenesis of FD. Recently, alterations to the gut microbiome have also been implicated to play an important role in the disease. Changes to the duodenal microbiota may either trigger or be a consequence of immune and neuronal disturbances observed in the disease, but the mechanisms of influence of small intestinal flora on gastrointestinal function and symptomatology are unknown. PURPOSE This review summarizes and synthesizes the literature on the link between the microbiota, low-grade inflammatory changes in the duodenum and FD. This review is not intended to provide a complete overview of FD or the small intestinal microbiota, but instead outline some of the key conceptual advances in understanding the interactions between altered gastrointestinal bacterial communities; dietary factors; host immune activation; and stimulation of the gut-brain axes in patients with FD versus controls. Current and emerging treatment approaches such as dietary interventions and antibiotic or probiotic use that have demonstrated symptom benefits for patients are reviewed, and their role in modulating the host-microbiota is discussed. Finally, suggested opportunities for diagnostic and therapeutic improvements for patients with this condition are presented.
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Affiliation(s)
- Georgia Brown
- School of Medicine and Public HealthUniversity of NewcastleNewcastleNew South WalesAustralia,AGIRA (Australian Gastrointestinal Research Alliance)NewcastleNew South WalesAustralia,NHMRC Centre of Research Excellence in Digestive HealthNewcastleNew South WalesAustralia
| | - Emily C. Hoedt
- AGIRA (Australian Gastrointestinal Research Alliance)NewcastleNew South WalesAustralia,NHMRC Centre of Research Excellence in Digestive HealthNewcastleNew South WalesAustralia,School of Biomedical Sciences and PharmacyUniversity of NewcastleNewcastleNew South WalesAustralia,Hunter Medical Research InstituteNew Lambton HeightsNewcastleNew South WalesAustralia
| | - Simon Keely
- AGIRA (Australian Gastrointestinal Research Alliance)NewcastleNew South WalesAustralia,NHMRC Centre of Research Excellence in Digestive HealthNewcastleNew South WalesAustralia,School of Biomedical Sciences and PharmacyUniversity of NewcastleNewcastleNew South WalesAustralia,Hunter Medical Research InstituteNew Lambton HeightsNewcastleNew South WalesAustralia
| | - Ayesha Shah
- AGIRA (Australian Gastrointestinal Research Alliance)NewcastleNew South WalesAustralia,NHMRC Centre of Research Excellence in Digestive HealthNewcastleNew South WalesAustralia,Faculty of Medicine and Faculty of Health and Behavioural SciencesThe University of QueenslandSt. LuciaQueenslandAustralia
| | - Marjorie M. Walker
- School of Medicine and Public HealthUniversity of NewcastleNewcastleNew South WalesAustralia,AGIRA (Australian Gastrointestinal Research Alliance)NewcastleNew South WalesAustralia,NHMRC Centre of Research Excellence in Digestive HealthNewcastleNew South WalesAustralia
| | - Gerald Holtmann
- AGIRA (Australian Gastrointestinal Research Alliance)NewcastleNew South WalesAustralia,NHMRC Centre of Research Excellence in Digestive HealthNewcastleNew South WalesAustralia,Faculty of Medicine and Faculty of Health and Behavioural SciencesThe University of QueenslandSt. LuciaQueenslandAustralia,Department of Gastroenterology & HepatologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia
| | - Nicholas J. Talley
- School of Medicine and Public HealthUniversity of NewcastleNewcastleNew South WalesAustralia,AGIRA (Australian Gastrointestinal Research Alliance)NewcastleNew South WalesAustralia,NHMRC Centre of Research Excellence in Digestive HealthNewcastleNew South WalesAustralia,Hunter Medical Research InstituteNew Lambton HeightsNewcastleNew South WalesAustralia
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27
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Więcek M, Panufnik P, Kaniewska M, Lewandowski K, Rydzewska G. Low-FODMAP Diet for the Management of Irritable Bowel Syndrome in Remission of IBD. Nutrients 2022; 14:4562. [PMID: 36364824 PMCID: PMC9658010 DOI: 10.3390/nu14214562] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 10/24/2022] [Accepted: 10/27/2022] [Indexed: 10/19/2024] Open
Abstract
Approximately 30% of patients with quiescent inflammatory bowel disease (IBD) meet the diagnostic criteria for irritable bowel syndrome (IBS). The aim of this study was to evaluate the effectiveness of a low-FODMAP diet in patients who meet the diagnostic criteria for IBS whilst in IBD remission. A total of 200 patients in remission of IBD were included in the study. Sixty-five of these patients (32.5%) were diagnosed with IBS according to the R4DQ. On the patients who met the IBS diagnostic criteria, anthropometric measurements, laboratory tests and lactulose hydrogen breath tests were performed. A low-FODMAP diet was introduced for 6 weeks. Of the 59 patients with IBS diagnosed at baseline for whom data were collected at the end of follow-up, after the low-FODMAP intervention IBS-like symptoms were not present in 66.1% (n = 39) (95% CI (53.4%; 76.9%)). The difference between the two groups (with SIBO at baseline (33 of 48 patients) and without SIBO at baseline (6 of 11 patients)) in the low-FODMAP diet's effectiveness was not statistically significant (p = 0.586). The low-FODMAP diet improved the gut symptoms of flatulence and diarrhea. It had no effect on the occurrence of constipation. In IBD patients in remission who meet the IBS criteria, the dietary intervention of a low-FODMAP diet is effective for a reduction in IBS-like symptoms, regardless of the coexistence of bacterial overgrowth.
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Affiliation(s)
- Martyna Więcek
- Clinical Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Subunit, Central Clinical Hospital of Ministry of the Interior and Administration, 02-507 Warsaw, Poland
| | - Paulina Panufnik
- Clinical Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Subunit, Central Clinical Hospital of Ministry of the Interior and Administration, 02-507 Warsaw, Poland
| | - Magdalena Kaniewska
- Clinical Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Subunit, Central Clinical Hospital of Ministry of the Interior and Administration, 02-507 Warsaw, Poland
| | - Konrad Lewandowski
- Clinical Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Subunit, Central Clinical Hospital of Ministry of the Interior and Administration, 02-507 Warsaw, Poland
| | - Grażyna Rydzewska
- Clinical Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Subunit, Central Clinical Hospital of Ministry of the Interior and Administration, 02-507 Warsaw, Poland
- Collegium Medicum, Jan Kochanowski University, 25-369 Kielce, Poland
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28
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Hepatic Encephalopathy in Cirrhotic Patients and Risk of Small Intestinal Bacterial Overgrowth: A Systematic Review and Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2022; 2022:2469513. [PMID: 36303585 PMCID: PMC9596239 DOI: 10.1155/2022/2469513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 10/04/2022] [Accepted: 10/05/2022] [Indexed: 11/23/2022]
Abstract
Background Hepatic encephalopathy (HE) is a neurological and psychiatric syndrome. Recent evidence suggests that HE is not only a disease of the liver and brain but is also related to the gut. Small intestinal bacterial overgrowth (SIBO) is well known to be associated with cirrhosis, but the relationship between SIBO and HE is unclear. We conducted this comprehensive systematic review and meta-analysis to determine the association between SIBO and HE in cirrhotic patients. Methods We conducted a comprehensive literature search of all studies on the association of SIBO and HE in cirrhotic patients using the PubMed and Embase electronic databases. Studies were screened, and relevant data were extracted and analysed. We calculated the number of cases of SIBO in patients with HE and controls. We then compared the prevalence of SIBO between the two groups to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Funnel plots were constructed to identify potential publication bias. Results Six studies with 414 participants (219 HE patients and 195 controls) met the inclusion criteria. The prevalence of SIBO in cirrhotic patients with HE was significantly higher than that in those without HE. The combined OR was 4.43 (95% CI 1.73-11.32, P = 0.002). The heterogeneity was moderate (I2 = 66%), and the funnel plot suggested no significant publication bias. Subgroup analysis showed that the OR was 1.95 (95% CI 0.63–6.09) in studies using the lactulose breath test (LBT) and 7.60 (95% CI 3.50–16.50) in studies using the glucose breath test (GBT). The prevalence of SIBO in cirrhotic patients was also related to the severity of liver disease. Conclusions Our meta-analysis identified a strong association between SIBO and HE, and the risk of SIBO was 4.43 times higher among cirrhotic patients with HE than among those without HE. SIBO could be a predisposing factor for the development of HE in cirrhotic patients. Therefore, the importance of SIBO should be emphasized in patients with HE.
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29
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Khan MZ, Lyu R, McMichael J, Gabbard S. Chronic Intestinal Pseudo-Obstruction Is Associated with Intestinal Methanogen Overgrowth. Dig Dis Sci 2022; 67:4834-4840. [PMID: 35001241 DOI: 10.1007/s10620-021-07343-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 11/22/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Chronic intestinal pseudo-obstruction (CIP) is a rare motility disorder characterized by dilated small bowel in the absence of mechanical obstruction. CIP has a known association with small intestinal bacterial overgrowth (SIBO); however, data regarding association with specific subtypes such as methane-positive (M+) and hydrogen-positive (H+) SIBO are limited. Therefore, we conducted this study to characterize subtypes of SIBO in CIP and compare them with non-CIP patients. AIMS The aim is to explore the association and prevalence of hydrogen and methane subtypes of SIBO in patients with CIP. METHODS A retrospective chart review was conducted for 494 patients who underwent glucose breath tests (GBT) in 2019. CIP was diagnosed based on clinical suspicion and after ruling out mechanical obstruction. We also reviewed demographic data, including age, gender, body mass index, tobacco and alcohol history, medical comorbidities, use of proton pump inhibitors, and history of colectomy. RESULTS Among 494 patients, 7.7% (38) had CIP. The prevalence of M+ GBT in CIP patients was higher compared with non-CIP patients, and it was significant [52.6% (20/38) versus 11.8% (54/456), p < 0.001]. The prevalence of H+ GBT in our cohort of CIP patients was similar to that of non-CIP patients [23.7% (9/38) versus 25.7% (117/456), p = 0.941]. CONCLUSION The prevalence of methane-positive GBT was higher in CIP patients than in patients without CIP. This finding further strengthens the hypothesis that the relationship between motility disorders and methanogen overgrowth is facilitative.
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Affiliation(s)
| | - Ruishen Lyu
- Department of Health Sciences, Cleveland Clinic, Cleveland, OH, USA
| | - John McMichael
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Scott Gabbard
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
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30
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Shah A, Thite P, Hansen T, Kendall BJ, Sanders DS, Morrison M, Jones MP, Holtmann G. Links between celiac disease and small intestinal bacterial overgrowth: A systematic review and meta-analysis. J Gastroenterol Hepatol 2022; 37:1844-1852. [PMID: 35734803 PMCID: PMC9795979 DOI: 10.1111/jgh.15920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 06/19/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND AIM Symptoms of small intestinal bacterial overgrowth (SIBO) and celiac disease (CeD) often overlap, and studies suggest a link between SIBO and CeD. We thus conducted a systematic review and meta-analysis to compare SIBO prevalence in CeD patients and controls and assessed effects of antimicrobial therapy on gastrointestinal symptoms in SIBO positive CeD patients. METHODS Electronic databases were searched until February 2022 for studies reporting SIBO prevalence in CeD. Prevalence rates, odds ratio (OR), and 95% confidence intervals (CI) of SIBO in CeD and controls were calculated. RESULTS We included 14 studies, with 742 CeD patients and 178 controls. The pooled prevalence of SIBO in CeD was 18.3% (95% CI: 11.4-28.1), with substantial heterogeneity. Including case-control studies with healthy controls, SIBO prevalence in CeD patients was significantly increased (OR 5.1, 95% CI: 2.1-12.4, P = 0.0001), with minimal heterogeneity. Utilizing breath tests, SIBO prevalence in CeD patients was 20.8% (95% CI: 11.9-33.7), almost two-fold higher compared with culture-based methods at 12.6% (95% CI: 5.1-28.0), with substantial heterogeneity in both analyses. SIBO prevalence in CeD patients nonresponsive to a gluten free diet (GFD) was not statistically higher as compared with those responsive to GFD (OR 1.5, 95% CI: 0.4-5.0, P = 0.511). Antibiotic therapy of SIBO positive CeD patients resulted in improvement in gastrointestinal symptoms in 95.6% (95% CI: 78.0-99.9) and normalization of breath tests. CONCLUSIONS This study suggests a link between SIBO and CeD. While SIBO could explain nonresponse to a GFD in CeD, SIBO prevalence is not statistically higher in CeD patients non-responsive to GFD. The overall quality of the evidence is low, mainly due to substantial "clinical heterogeneity" and the limited sensitivity/specificity of the available diagnostic tests.
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Affiliation(s)
- Ayesha Shah
- Faculty of MedicineThe University of QueenslandBrisbaneQueenslandAustralia,Department of Gastroenterology and HepatologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia,Translational Research InstituteWoolloongabbaQueenslandAustralia
| | - Parag Thite
- Faculty of MedicineThe University of QueenslandBrisbaneQueenslandAustralia,Department of Gastroenterology and HepatologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia
| | - Teressa Hansen
- Faculty of MedicineThe University of QueenslandBrisbaneQueenslandAustralia,Department of Gastroenterology and HepatologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia,Translational Research InstituteWoolloongabbaQueenslandAustralia
| | - Bradley J Kendall
- Faculty of MedicineThe University of QueenslandBrisbaneQueenslandAustralia,Department of Gastroenterology and HepatologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia
| | - David S Sanders
- Academic Unit of GastroenterologySheffield Teaching Hospitals NHS Foundation TrustSheffieldUK
| | - Mark Morrison
- Faculty of MedicineThe University of QueenslandBrisbaneQueenslandAustralia,Department of Gastroenterology and HepatologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia,Diamantina InstituteThe University of QueenslandBrisbaneQueenslandAustralia
| | - Michael P Jones
- Department of PsychologyMacquarie UniversitySydneyNew South WalesAustralia
| | - Gerald Holtmann
- Faculty of MedicineThe University of QueenslandBrisbaneQueenslandAustralia,Department of Gastroenterology and HepatologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia,Translational Research InstituteWoolloongabbaQueenslandAustralia
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31
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Ivashkin VT, Maev IV, Abdulganieva DI, Alekseeva OP, Alekseenko SA, Zolnikova OY, Korochanskaya NV, Medvedev OS, Poluektova EA, Simanenkov VI, Trukhmanov AS, Khlynov IB, Tsukanov VV, Shifrin OS, Ivashkin KV, Lapina TL, Maslennikov RV, Fadeeva MV, Ulyanin AI. Practical Recommendation of the Scientific Сommunity for Human Microbiome Research (CHMR) and the Russian Gastroenterological Association (RGA) on Small Intestinal Bacterial Overgrowth in Adults. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2022; 32:68-85. [DOI: 10.22416/1382-4376-2022-32-3-68-85] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/26/2024]
Abstract
Aim. To optimize the choice of treatment strategies by physicians and gastroenterologists to improve treatment and prevention of small intestinal bacterial overgrowth (SIBO) in adults.Key points. SIBO is a condition characterized by an increased amount and/or abnormal composition of the microbiota in the small intestine. Clinically, the syndrome is manifested by nonspecific gastroenterological complaints and the development of malabsorption syndrome. Most often, SIBO is associated with various chronic non- infectious diseases (both diseases of the gastrointestinal tract, and the cardiovascular system and the neuromuscular apparatus) and can affect the severity of their symptoms. Specific methods for diagnosing SIBO are the culture method and breath tests. The main approaches to the treatment of SIBO include the elimination of the underlying cause of its occurrence, the use of antibacterial drugs and adherence to dietary recommendations (elemental diet).Conclusion. Small intestinal bacterial overgrowth is common in patients with various diseases, but has non-specific manifestations, so proper diagnosis of this condition is required. SIBO therapy involves prescription of antibacterial agents, the most studied of which is the non-absorbable antibiotic rifaximin-α.
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Affiliation(s)
- V. T. Ivashkin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - I. V. Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | | | | | | | - O. Yu. Zolnikova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | - O. S. Medvedev
- Lomonosov Moscow State University;
Institute of Experimental Cardiology of National Medical Research Center of Cardiology
| | - E. A. Poluektova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | - A. S. Trukhmanov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | - V. V. Tsukanov
- Research Institute for Medical Problems in the North — Division of Krasnoyarsk Scientific Centre of the Siberian Branch of the RAS
| | - O. S. Shifrin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - K. V. Ivashkin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - T. L. Lapina
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - R. V. Maslennikov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - M. V. Fadeeva
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - A. I. Ulyanin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
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32
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Wils P, Caron B, D’Amico F, Danese S, Peyrin-Biroulet L. Abdominal Pain in Inflammatory Bowel Diseases: A Clinical Challenge. J Clin Med 2022; 11:4269. [PMID: 35893357 PMCID: PMC9331632 DOI: 10.3390/jcm11154269] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 07/15/2022] [Accepted: 07/15/2022] [Indexed: 02/01/2023] Open
Abstract
Up to 60% of inflammatory bowel disease (IBD) patients experience abdominal pain in their lifetime regardless of disease activity. Pain negatively affects different areas of daily life and particularly impacts the quality of life of IBD patients. This review provides a comprehensive overview of the multifactorial etiology implicated in the chronic abdominal pain of IBD patients including peripheral sensitization by inflammation, coexistent irritable bowel syndrome, visceral hypersensitivity, alteration of the brain-gut axis, and the multiple factors contributing to pain persistence. Despite the optimal management of intestinal inflammation, chronic abdominal pain can persist, and pharmacological and non-pharmacological approaches are necessary. Integrating psychological support in care models in IBD could decrease disease burden and health care costs. Consequently, a multidisciplinary approach similar to that used for other chronic pain conditions should be recommended.
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Affiliation(s)
- Pauline Wils
- Department of Gastroenterology, Claude Huriez Hospital, University of Lille, F-59000 Lille, France
| | - Bénédicte Caron
- Department of Gastroenterology, University of Lorraine, CHRU-Nancy, F-54000 Nancy, France; (B.C.); (L.P.-B.)
- Department of Gastroenterology, University of Lorraine, Inserm, NGERE, F-54000 Nancy, France
| | - Ferdinando D’Amico
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, 20132 Milan, Italy; (F.D.); (S.D.)
- Department of Biomedical Sciences, Humanitas University, 20090 Milan, Italy
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, 20132 Milan, Italy; (F.D.); (S.D.)
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, University of Lorraine, CHRU-Nancy, F-54000 Nancy, France; (B.C.); (L.P.-B.)
- Department of Gastroenterology, University of Lorraine, Inserm, NGERE, F-54000 Nancy, France
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Ahmed JF, Padam P, Ruban A. Aetiology, diagnosis and management of small intestinal bacterial overgrowth. Frontline Gastroenterol 2022; 14:149-154. [PMID: 36818787 PMCID: PMC9933597 DOI: 10.1136/flgastro-2022-102163] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 06/27/2022] [Indexed: 02/24/2023] Open
Abstract
Small intestinal bacterial overgrowth is a small bowel disorder characterised by excessive amounts of bacteria populating the small intestine leading to symptoms of abdominal pain, bloating and change in bowel habit. This creates some degree of diagnostic uncertainty due to the overlap of these symptoms with numerous other gastrointestinal conditions. Quantitative culture of jejunal aspirates is the gold standard diagnostic test but has largely been replaced by glucose and lactulose breath tests due to their relative ease and accessibility. The approach to treatment centres around reducing bacterial numbers through antibiotic therapy and managing any predisposing factors. Further research is required in order to define the optimum antibiotic choice and duration of therapy as well as the potential diagnostic utility of home breath testing and capsule-based technology.
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Affiliation(s)
- Jabed Foyez Ahmed
- Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK
| | - Pritpal Padam
- Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK
| | - Aruchuna Ruban
- Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK
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34
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Evidence-Based and Emerging Diet Recommendations for Small Bowel Disorders. Am J Gastroenterol 2022; 117:958-964. [PMID: 35404303 PMCID: PMC9169759 DOI: 10.14309/ajg.0000000000001764] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 04/01/2022] [Indexed: 02/06/2023]
Abstract
Diet plays a key role in the manifestation and severity of gastrointestinal symptoms, with increasing research interest on the role of diet in small bowel disorders. There are predominantly 3 small bowel conditions that have potential dietary interventions. Self-reported nonceliac gluten/wheat sensitivity is prevalent. Although gluten is believed to be a potential trigger for symptoms, other components of wheat may also be triggers, including fructans, alpha-amylase trypsin inhibitors, and wheat germ agglutinins. The diagnosis can be challenging, given the lack of validated biomarkers. A gluten-free diet that excludes the abovementioned triggers is the cornerstone of treatment; however, unlike celiac disease, there is uncertainty about the level of adherence or whether the gluten-free diet is a lifelong intervention. Several primary gastrointestinal disorders are associated with an increase in inflammatory cells including eosinophils. Diet seems to be an important driver of disease pathogenesis in eosinophilic gastroenteritis, with elimination and elemental diets showing promise in management, with further robust trials required. Small intestinal bacterial overgrowth is an example of microbial dysbiosis, with renewed interest in diet being postulated to cause an adaptive change of the microbes colonizing the small intestine. However, the diagnosis of small intestinal bacterial overgrowth is limited by a lack of sensitive and specific tests, with significant knowledge gaps in relation to therapeutic measures to manage and cure small intestinal bacterial overgrowth. Currently, antimicrobials are the established management option. There have been significant clinical advances in dietary interventions related to the small bowel, but this area is currently a novel and advancing field for both patients and clinicians.
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Concomitant Irritable Bowel Syndrome Does Not Influence the Response to Antimicrobial Therapy in Patients with Functional Dyspepsia. Dig Dis Sci 2022; 67:2299-2309. [PMID: 34392491 DOI: 10.1007/s10620-021-07149-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 05/03/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Antimicrobial therapy improves symptoms in patients with irritable bowel syndrome (IBS), but the efficacy in functional dyspepsia (FD) is largely unknown. While FD and IBS frequently overlap, it is unknown if concomitant IBS in FD alters the response to antimicrobial therapy in FD. Thus, we aimed to assess and compare the effect of antimicrobial therapy on visceral sensory function and symptom improvement in FD patients with and without IBS. METHODS Adult patients with FD with or without IBS received rifaximin 550 mg BD for 10 days, followed by a 6-week follow-up period. The total gastrointestinal symptom score as measured by the SAGIS (Structured Assessment of Gastrointestinal Symptoms) questionnaire and subscores (dyspepsia, diarrhea, and constipation), symptom response to a standardized nutrient challenge and normalization of the glucose breath tests were measured. RESULTS Twenty-one consecutive adult patients with FD and 14/21 with concomitant IBS were recruited. Treatment with rifaximin resulted in a significant (p = 0.017) improvement in the total SAGIS score from 34.7 (± 15.4) at baseline to 26.0 (± 16.8) at 2 weeks and 25.6 (± 17.8) at 6 weeks post-treatment. Similarly, compared to baseline there was a statistically significant improvement in SAGIS subscores for dyspepsia and diarrhea (all p < 0.05) and effects persisted for 6 weeks post-treatment. Similarly, the symptom score (and subscores) following a standardized nutrient challenge improved significantly (p < 0.001) 2 weeks post-treatment. The presence of concomitant IBS did not significantly influence the improvement of symptoms after antibiotic therapy (all p > 0.5). CONCLUSIONS In FD patients, the response to antimicrobial therapy with rifaximin is not influenced by concomitant IBS symptoms.
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Souza C, Rocha R, Cotrim HP. Diet and intestinal bacterial overgrowth: Is there evidence? World J Clin Cases 2022; 10:4713-4716. [PMID: 35801041 PMCID: PMC9198866 DOI: 10.12998/wjcc.v10.i15.4713] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 08/28/2021] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
The intestinal microbiota and its role in health and disease processes have been the subject of several studies. It is known that changes in the intestinal microbiota occur due to several factors, such as the use of medication, age, lifestyle and diseases, which can modify intestinal homeostasis and lead to excessive growth of bacteria in the small intestine, triggering a clinical condition called small bowel bacterial overgrowth (SIBO). Individuals with SIBO may present gastrointestinal symptoms ranging from nausea, diarrhea and/or constipation, and flatulence to distension and abdominal pain, resulting from poor absorption of nutrients or changes in intestinal permeability. The gold-standard treatment is based on the use of antibiotics to eradicate bacterial overgrowth. Some studies have evaluated diets in the treatment of SIBO; however, the studies are of low methodological quality, making extrapolation of the results to clinical practice unfeasible. Thus, there is still not enough scientific evidence to support a specific type of diet for the treatment of SIBO.
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Affiliation(s)
- Claudineia Souza
- Programa de Pós graduação em Medicina e Saúde, Universidade Federal da Bahia, Salvador 40110-060, BA, Brazil
| | - Raquel Rocha
- Sciences of Nutrition, Federal University of Bahia, Salvador 40110-060, BA, Brazil
| | - Helma Pinchemel Cotrim
- Programa de Pós graduação em Medicina e Saúde, Universidade Federal da Bahia, Salvador 40110-060, BA, Brazil
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Fairbrass KM, Selinger CP, Gracie DJ, Ford AC. Prevalence and impact of Rome IV versus Rome III irritable bowel syndrome in patients with inflammatory bowel disease. Neurogastroenterol Motil 2022; 34:e14256. [PMID: 34472157 DOI: 10.1111/nmo.14256] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 08/11/2021] [Accepted: 08/19/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Irritable bowel syndrome (IBS)-type symptoms are common in inflammatory bowel disease (IBD), but few studies have examined the prevalence and impact of IBS-type symptoms in IBD according to Rome IV criteria. METHODS We collected demographic, symptom (Rome III, Rome IV, and clinical disease activity indices), psychological (anxiety, depression, and somatization), and quality of life data from 973 IBD patients. Medical records were reviewed to document disease type, extent/location, behavior, medical therapy, and antidepressant or opioid use. We compared characteristics of individuals with no IBS-type symptoms, Rome III IBS-type symptoms, and Rome IV IBS-type symptoms. KEY RESULTS In total, 302 (31.0%) patients met the Rome III criteria for IBS, and 172 (17.7%) met Rome IV criteria. Those with IBS-type symptoms were younger, more likely to be female, and had higher rates of antidepressant (p = 0.006) or opioid use (p = 0.001). Rome IV IBS-type symptoms were associated with symptoms of mood disorders, flare of disease activity, and lower quality of life scores (p < 0.001 for all analyses). Compared with Rome III criteria, those with Rome IV IBS-type symptoms had significantly higher rates of anxiety (p < 0.001), depression (p = 0.002), and somatization (p < 0.001), lower quality of life scores (p < 0.001) and were more likely to have CD (p = 0.011), with ileal distribution (p = 0.006). CONCLUSIONS AND INFERENCES Rome IV IBS-type symptoms are associated with increased psychological co-morbidity, lower quality of life scores, and higher rates of antidepressant or opioid use. This is a cohort potentially at risk of adverse clinical outcomes and should be a focus for future research.
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Affiliation(s)
- Keeley M Fairbrass
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research, St. James's, University of Leeds, Leeds, UK
| | | | - David J Gracie
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research, St. James's, University of Leeds, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research, St. James's, University of Leeds, Leeds, UK
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Click B, Barnes EL, Cohen BL, Sands BE, Hanson JS, Rubin DT, Dubinsky MC, Regueiro M, Gazis D, Crawford JM, Long MD. Objective disease activity assessment and therapeutic drug monitoring prior to biologic therapy changes in routine inflammatory bowel disease clinical practice: TARGET-IBD. BMC Gastroenterol 2022; 22:71. [PMID: 35183108 PMCID: PMC8858477 DOI: 10.1186/s12876-022-02143-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 02/06/2022] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) treatment paradigms recommend objective disease activity assessment and reactive therapeutic drug monitoring (TDM) prior to changes in biologic therapy. We aimed to describe objective marker and TDM assessment in routine clinical practice prior to biologic therapeutic changes in adult IBD patients. METHODS TARGET-IBD is a prospective longitudinal cohort of over 2100 IBD patients receiving usual care at 34 US academic or community centers enrolled between June 2017 and October 2019 who received biologic therapy and had a dose change or biologic discontinuation for lack of efficacy. Objective markers of disease activity within 12 weeks prior included fecal calprotectin, C-reactive protein (CRP), endoscopy, computed tomography (CT) and magnetic resonance imaging (MRI). TDM data for infliximab or adalimumab was obtained. RESULTS 525 patients (71.4% Crohn's disease [CD], 28.6% ulcerative colitis [UC]) receiving biologic therapy underwent dose change (55.6%) or discontinuation (44.4%) for lack of efficacy. The majority were Caucasian (85.7%), 18-39 years old (52.2%), privately insured (81.5%), and at academic centers (73.7%). For dose changes, 67.5% had at least one objective disease activity assessment or TDM in the 12 weeks prior (CD 67.9%, UC 66.2%; P = 0.79). The most common objective marker was CRP in both CD (39.1%) and UC (54.5%). CRP and calprotectin were used significantly more in UC (P = 0.02 and P = 0.03). TDM was obtained in 30.7% (28.8% UC, 31.4% CD; P = 0.72) prior to dose change. For biologic discontinuation, 79.4% patients underwent objective assessment or TDM prior. In CD, CRP (46.3%) was most common, and CT (P = 0.03) and MRI (P < 0.001) were significantly more frequent than in UC. TDM was performed in 40.1% of patients (43.5% UC, 38.0% CD, P = 0.49) prior to discontinuation. Among all participants with dose change or discontinuation, endoscopy was performed in 29.3% with CD and 31.3% with UC. Academic care setting was associated with objective assessment before therapy change (OR 1.59, 95% CI 1.01-2.50). CONCLUSION Nearly one-third of patients undergoing a biologic dose change or discontinuation do not undergo objective disease activity assessment or TDM. Assessment choice differs by disease. Future studies assessing the impact of such practices on long-term outcomes are needed.
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Affiliation(s)
- Benjamin Click
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, USA
| | | | - Benjamin L Cohen
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, USA
| | | | | | | | | | - Miguel Regueiro
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, USA
| | - Derek Gazis
- Target RWE Health Evidence Solutions, 2520 Meridian Pkwy, Suite 105, Durham, NC, 27713, USA
| | - Julie M Crawford
- Target RWE Health Evidence Solutions, 2520 Meridian Pkwy, Suite 105, Durham, NC, 27713, USA.
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Ghoshal UC, Yadav A, Fatima B, Agrahari AP, Misra A. Small intestinal bacterial overgrowth in patients with inflammatory bowel disease: A case-control study. Indian J Gastroenterol 2022; 41:96-103. [PMID: 34390471 DOI: 10.1007/s12664-021-01211-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 06/07/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND Though small intestinal bacterial overgrowth (SIBO) is known in inflammatory bowel disease (IBD), the data on it are scanty and have limitations. METHODS Data on IBD patients undergoing glucose hydrogen breath test (GHBT) were retrospectively analyzed to evaluate the frequency and risk factors of SIBO in IBD compared to 66 healthy controls. RESULTS Patients with IBD (n=86; 45 ulcerative colitis [UC] and 41 Crohn's disease [CD]) more often had SIBO on GHBT than the healthy subjects (16/86 [18.6%] vs. 1/66 [1.5%]; p=0.002). SIBO was commoner among patients with CD than UC (14/41 [34.1%] vs. 2/45 [4.4%]; p=0.001). The frequency of SIBO among UC patients was comparable to healthy subjects (2/45 [4.4%] vs. 1/66 [1.5%]; p=not significant [NS]). Patients with CD than those with UC had higher values of maximum breath hydrogen and a greater area under the curve for breath hydrogen. Other factors associated with SIBO included female gender (11/16 [68.8%] with vs. 21/70 [30%] without SIBO; p=0.003), and having undergone surgery (8/16 [50%] vs. 6/70 [8.6%]; p=0.0002). SIBO patients had lower levels of total serum protein and albumin than those without SIBO (6.2 ± 1.5 g/dL vs. 7.0 ± 0.9 g/dL, respectively; p=0.009 and 3.5 ± 0.9 g/dL vs. 4.0 ± 0.6 g/dL, respectively; p=0.02). CD, female gender, and surgery for IBD tended to be the independent factors associated with SIBO among IBD patients on multivariate analysis. CONCLUSIONS Patients with IBD, particularly CD, female, and those having undergone surgery, have a higher risk of SIBO than the healthy controls.
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Affiliation(s)
- Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226 014, India.
| | - Ankur Yadav
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226 014, India
| | - Bushra Fatima
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226 014, India
| | - Anand Prakash Agrahari
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226 014, India
| | - Asha Misra
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226 014, India
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40
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Shah A, Holtmann G. Small intestinal bacterial overgrowth in inflammatory bowel disease. Indian J Gastroenterol 2022; 41:23-29. [PMID: 35031976 DOI: 10.1007/s12664-021-01235-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 12/06/2021] [Indexed: 02/04/2023]
Affiliation(s)
- Ayesha Shah
- Faculty of Medicine and Faculty of Health and Behavioral Sciences, The University of Queensland, Brisbane, Australia. .,Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia. .,AGIRA (Australian Gastrointestinal Research Alliance) and the NHMRC Centre of Research Excellence in Digestive Health, Brisbane, Australia.
| | - Gerald Holtmann
- Faculty of Medicine and Faculty of Health and Behavioral Sciences, The University of Queensland, Brisbane, Australia.,Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia.,AGIRA (Australian Gastrointestinal Research Alliance) and the NHMRC Centre of Research Excellence in Digestive Health, Brisbane, Australia
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41
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Singh A, Wall C, Levine A, Midha V, Mahajan R, Sood A. Nutritional screening and assessment in inflammatory bowel disease. Indian J Gastroenterol 2022; 41:5-22. [PMID: 35031977 DOI: 10.1007/s12664-021-01223-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 09/24/2021] [Indexed: 02/04/2023]
Abstract
Inflammatory bowel disease (IBD) is associated with increased risk of malnutrition and sarcopenia. Both malnutrition and sarcopenia negatively impact the clinical course, quality of life, response to therapy, and surgical outcomes in patients with IBD. This review article highlights the importance of nutritional assessment in patients with IBD and also discusses the different nutritional screening and assessment tools, and measures to detect sarcopenia in relation to IBD. Identification of malnutrition and sarcopenia will allow prioritization of the corrective actions, such as nutritional rehabilitation, to improve clinical outcomes. An approach to the evaluation of nutritional status in patients with IBD is also suggested.
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Affiliation(s)
- Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, 141 001, India
| | - Catherine Wall
- Department of Medicine and Department of Human Nutrition, University of Otago, Christchurch, New Zealand
| | - Arie Levine
- Pediatric Gastroenterology and Nutrition Unit, Pediatric IBD Center, Wolfson Medical Center Holon, Tel Aviv University, Tel Aviv, Israel
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College, Ludhiana, 141 001, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, 141 001, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, 141 001, India.
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Gandhi A, Shah A, Jones MP, Koloski N, Talley NJ, Morrison M, Holtmann G. Methane positive small intestinal bacterial overgrowth in inflammatory bowel disease and irritable bowel syndrome: A systematic review and meta-analysis. Gut Microbes 2022; 13:1933313. [PMID: 34190027 PMCID: PMC8253120 DOI: 10.1080/19490976.2021.1933313] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Several studies reported a potential role of methane producing archaea in the pathophysiology of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). We conducted a systematic review and meta-analysis to assess the prevalence of methane positive small intestinal bacterial overgrowth (SIBO) in IBS and IBD compared with controls. MEDLINE (PubMed) and Embase electronic databases were searched from inception until March 2021 for case-control and prevalence studies reporting SIBO in IBS and IBD. We extracted data from published studies and calculated pooled prevalence of SIBO in IBS or IBD, odds ratios (OR), and 95% CIs, utilizing a random effects model. The final dataset included 17 independent studies assessing the prevalence of methane positive SIBO in 1,653 IBS-patients and 713 controls, and 7 studies assessing the prevalence of methane positive SIBO in 626 IBD-patients and 497 controls, all utilizing breath test for SIBO diagnosis. Prevalence of methane positive SIBO in IBS and IBD was 25.0% (95% CI 18.8-32.4) and 5.6% (95% CI 2.6-11.8), respectively. Methane positive SIBO in IBS was not increased compared to controls (OR = 1.2, 95% CI 0.8-1.7, P = .37) but was significantly more prevalent in IBS-C as compared to IBS-D (OR = 3.1, 95% CI 1.7-5.6, P = .0001). The prevalence of methane-positive SIBO in patients with IBD was 3-fold lower at 7.4% (95% CI 5.4-9.8) compared to 23.5% (95% CI 19.8-27.5) in controls. The prevalence of methane positive SIBO was significantly lower in Crohn's disease as compared to ulcerative colitis, (5.3%, 95% CI 3.0-8.5 vs. 20.2%, 95% CI 12.8-29.4). This systematic review and meta-analysis suggests methane positivity on breath testing is positively associated with IBS-C and inversely with IBD. However, the quality of evidence is low largely due to clinical heterogeneity of the studies. Thus, causality is uncertain and further studies are required.
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Affiliation(s)
- Arjun Gandhi
- Faculty of Medicine, The University of Queensland, Queensland, Australia,Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - Ayesha Shah
- Faculty of Medicine, The University of Queensland, Queensland, Australia,Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia,Translational Research Institute, Brisbane, Queensland, Australia
| | - Michael P. Jones
- Department of Psychology, Macquarie University, Sydney, New South Wales, Australia
| | - Natasha Koloski
- Faculty of Medicine, The University of Queensland, Queensland, Australia,Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia,Translational Research Institute, Brisbane, Queensland, Australia
| | - Nicholas J. Talley
- Faculty of Health and Medicine, The University of Newcastle, Newcastle, Australia
| | - Mark Morrison
- Faculty of Medicine, The University of Queensland, Queensland, Australia,Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia,University of Queensland, Diamantina Institute, Brisbane, Queensland, Australia
| | - Gerald Holtmann
- Faculty of Medicine, The University of Queensland, Queensland, Australia,Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia,Translational Research Institute, Brisbane, Queensland, Australia,CONTACT Gerald Holtmann Brisbane Department of Gastroenterology and Hepatology & University of Queensland Ipswich Road, Woolloongabba, Queensland, Australia
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Stepanov Y, Titova M, Nedzvetska N. Prevalence of small intestinal bacterial overgrowth syndrome among patients with inflammatory bowel disease and its impact on nutritional status and clinical manifestations. Gastroenterology 2022; 55:166-171. [DOI: 10.22141/2308-2097.55.3.2021.241586] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Background. In recent years, there has been high interest in the prevalence of small intestinal bacterial overgrowth (SIBO) syndrome in various populations. Chronic inflammatory bowel disease (IBD) is known to be a heterogeneous group of disorders, with a high degree of geographical variability in terms of symptoms, nature of progression, clinical manifestations, or combination with other types of pathologies. Since the involvement of the intestinal microbiome plays an important role in the etiopathogenesis of inflammatory bowel disease, the combination of SIBO and IBD is increasingly being considered and studied recently. Since the symptoms of both pathological conditions are significantly echoed, and therefore exacerbated by the combination, the manifestations of malnutrition become more pronounced, which negatively affects the nutritional status of patients with IBD. The purpose of the study is to determine the frequency of SIBO in patients with IBD depending on the nosological forms and to investigate its effect on clinical and laboratory indicators of nutritional status and clinical manifestations. Materials and methods. We examined 100 patients with IBD, aged 19 to 79 years, on average (42.54 ± 1.50) years, including 70 patients with ulcerative colitis (UC), and 30 — with Crohn’s disease (CD). All patients underwent general clinical examination, anthropometric measurements, general and biochemical blood tests (with the determination of total protein, albumin, prealbumin). To characterize the state of the small intestine microbiota (presence of SIBO), all patients underwent a hydrogen breath test with glucose loading using a Gastro+ Gastrolyzer gas analyzer from Bedfont Scientific Ltd (UK). Results. The analysis of SIBO frequency showed the changes in the state of the small intestinal microflora in 45 % of patients with IBD. The prevalence of SIBO was higher in the group of patients with CD — 53.3 % (16) than in the group with UC — 41.4 % (29). The presence of SIBO in the group of patients with UC had statistical significance and a direct correlation with the duration of the disease — (9.3 ± 6.2) versus (2.9 ± 3.1) years (p = 0.001, r = 0.55). There was a decrease in weight and body mass index (BMI) in patients with SIBO, especially in patients with Crohn’s disease, and accounted for (19.8 ± 3.5) kg/m2. There was a significant difference between the levels of total protein in patients with SIBO and without it, both in the basic group and in the group of UC: (65.8 ± 8.4) vs. (70.2 ± 8.2) g/l (p=0.009, r = –0.232) and (66.5 ± 8.3) vs. (70.7 ± 7.4) g/l (p = 0.029), respectively, and albumin levels were reduced in both nosological groups. No relationship was found between the severity of abdominal pain and the presence of SIBO. When SIBO was detected, the manifestations of flatulence significantly prevailed in patients with UC — 75.8 % (n=22), and diarrheal syndrome in patients with CD — 75 % (n = 12). Conclusions. The obtained results indicate a high prevalence of SIBO in patients with IBD. Patients with CD suffered from SIBO more often (53.3 %) than patients with UC (41.4%) (with a predominance of patients with severe disease). A direct correlation of SIBO with the disease duration in patients with UC (r = 0.55, р < 0.05) was revealed, which is explained by the violation of physiological barriers that prevent the emergence of SIBO, due to more episodes of exacerbation, long-term use of drugs and concomitant pathology with time. The negative impact of SIBO on nutritional status manifested in weight loss, reduced BMI and other anthropometric (mid-upper arm circumference, mid-arm muscle circumference, triceps skinfold) and laboratory (total protein, albumin, prealbumin) parameters in these patients. The most common symptoms in patients with IBD with SIBO were abdominal pain, diarrhea, and flatulence that reflected the typical clinical picture of SIBO.
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Ghoshal UC, Sachdeva S, Ghoshal U, Misra A, Puri AS, Pratap N, Shah A, Rahman MM, Gwee KA, Tan VPY, Ahmed T, Lee YY, Ramakrishna BS, Talukdar R, Rana SV, Sinha SK, Chen M, Kim N, Holtmann G. Asian-Pacific consensus on small intestinal bacterial overgrowth in gastrointestinal disorders: An initiative of the Indian Neurogastroenterology and Motility Association. Indian J Gastroenterol 2022; 41:483-507. [PMID: 36214973 PMCID: PMC9549446 DOI: 10.1007/s12664-022-01292-x] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 08/02/2022] [Indexed: 02/04/2023]
Abstract
In the clinical setting, small intestinal bacterial overgrowth (SIBO) is a frequent, but under-diagnosed entity. SIBO is linked to various gastrointestinal (GI) and non-GI disorders with potentially significant morbidity. The optimal management of SIBO is undefined while there is a lack of published consensus guidelines. Against this background, under the auspices of the Indian Neurogastroenterology and Motility Association (INMA), formerly known as the Indian Motility and Functional Diseases Association (IMFDA), experts from the Asian-Pacific region with extensive research and clinical experience in the field of gut dysbiosis including SIBO developed this evidence-based practice guideline for the management of SIBO utilizing a modified Delphi process based upon 37 consensus statements, involving an electronic voting process as well as face-to-face meetings and review of relevant supporting literature. These statements include 6 statements on definition and epidemiology; 11 on etiopathogenesis and pathophysiology; 5 on clinical manifestations, differential diagnosis, and predictors; and 15 on investigations and treatment. When the proportion of those who voted either to accept completely or with minor reservations was 80% or higher, the statement was regarded as accepted. The members of the consensus team consider that this guideline would be valuable to inform clinical practice, teaching, and research on SIBO in the Asian-Pacific region as well as in other countries.
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Affiliation(s)
- Uday C. Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014 India
| | - Sanjeev Sachdeva
- Department of Gastroenterology, G B Pant Hospital, New Delhi, 110 002 India
| | - Ujjala Ghoshal
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014 India
| | - Asha Misra
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014 India
| | | | | | - Ayesha Shah
- University of Queensland, Faculty of Medicine, and Princess Alexandra Hospital, Department of Gastroenterology and Hepatology, Brisbane, Queensland, Australia
| | - M. Masudur Rahman
- Sheikh Russel National Gastroliver Institute and Hospital, Dhaka, Bangladesh
| | - Kok Ann Gwee
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore ,Stomach, Liver and Bowel Centre, Gleneagles Hospital, Singapore, Singapore
| | - Victoria P Y Tan
- Faculty of Medicine, University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Tahmeed Ahmed
- International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
| | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia ,GI Function and Motility Unit, Hospital Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - B S Ramakrishna
- SIMS Institute of Gastroenterology, Hepatology, and Transplantation, SRM Institutes for Medical Science, Chennai, 600 026 India
| | - Rupjyoti Talukdar
- Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, 500 082 India
| | - S V Rana
- Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, 249 203 India
| | - Saroj K Sinha
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012 India
| | - Minhu Chen
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Gerald Holtmann
- University of Queensland, Faculty of Medicine, and Princess Alexandra Hospital, Department of Gastroenterology and Hepatology, Brisbane, Queensland, Australia
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Russo E, Giudici F, Ricci F, Scaringi S, Nannini G, Ficari F, Luceri C, Niccolai E, Baldi S, D'Ambrosio M, Ramazzotti M, Amedei A. Diving into Inflammation: A Pilot Study Exploring the Dynamics of the Immune-Microbiota Axis in Ileal Tissue Layers of Patients with Crohn's Disease. J Crohns Colitis 2021; 15:1500-1516. [PMID: 33611347 DOI: 10.1093/ecco-jcc/jjab034] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS The pathogenesis of Crohn's disease [CD] is still unclear. Disorders in the mucosal immunoregulation and its crosstalk with the microbiota may represent an important component in tissue injury. We aimed to characterize the molecular immune response distribution within the ileal layers and to evaluate the correlated microbiota in pathological/healthy settings comparing first surgery/relapse clinical conditions. METHODS We enrolled 12 CD patients. A comprehensive analysis of an ileal mucosa, submucosa and serosa broad-spectrum cytokine panel was performed through a multiplex approach. In addition, ileal microbiota composition was assessed through next generation sequencing. RESULTS We observed a distinct profile [of IL1-α, IL-1β, IL-4, IL-8, ICAM-1, E-Selectin, P-Selectin, IP-10, IL 6 and IL 18] across the CD vs healthy ileal layers; and a different distribution of IFN- γ, P-Selectin, IL-27 and IL-21 in first surgery vs relapse patients. In addition, the phylum Tenericutes, the family Ruminococcaceae, and the genera Mesoplasma and Mycoplasma were significantly enriched in the pathological setting. Significant microbiota differences were observed between relapse and first surgery patients regarding the class Bacteroidia, and the genera Prevotella, Flavobacterium, Tepidimonas and Escherichia/Shigella. Finally, the abundance of the genus Mycoplasma was positively correlated with IL-18. CONCLUSIONS We describe a dissimilarity of cytokine distribution and microbiota composition within CD and adjacent healthy ileal tissue layers and between first operation and surgical relapse. Our results give potential insight into the dynamics of the gut microbiota-immune axis in CD patients, leading to detection of new biomarkers.
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Affiliation(s)
- Edda Russo
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
| | - Francesco Giudici
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
| | - Federica Ricci
- Tumor Cell Biology Unit - Core Research Laboratory, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy
| | - Stefano Scaringi
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
| | - Giulia Nannini
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
| | - Ferdinando Ficari
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
| | - Cristina Luceri
- Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), Florence, Italy
| | - Elena Niccolai
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
| | - Simone Baldi
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
| | - Mario D'Ambrosio
- Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), Florence, Italy
| | - Matteo Ramazzotti
- Department of Biomedical, Experimental and Clinical "Mario Serio", Florence, Italy
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
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Basson AR, Rodriguez-Palacios A, Cominelli F. Artificial Sweeteners: History and New Concepts on Inflammation. Front Nutr 2021; 8:746247. [PMID: 34631773 PMCID: PMC8497813 DOI: 10.3389/fnut.2021.746247] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 08/23/2021] [Indexed: 12/12/2022] Open
Abstract
Since the introduction of artificial sweeteners (AS) to the North American market in the 1950s, a growing number of epidemiological and animal studies have suggested that AS may induce changes in gut bacteria and gut wall immune reactivity, which could negatively affect individuals with or susceptible to chronic inflammatory conditions such as inflammatory bowel disease (IBD), a disorder that has been growing exponentially in westernized countries. This review summarizes the history of current FDA-approved AS and their chemical composition, metabolism, and bacterial utilization, and provides a scoping overview of the disease mechanisms associated with the induction or prevention of inflammation in IBD. We provide a general outlook on areas that have been both largely and scarcely studied, emerging concepts using silica, and describe the effects of AS on acute and chronic forms of intestinal inflammation.
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Affiliation(s)
- Abigail Raffner Basson
- Division of Gastroenterology and Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, United States
- Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
| | - Alexander Rodriguez-Palacios
- Division of Gastroenterology and Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, United States
- Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
- Mouse Models, Silvio O'Conte Cleveland Digestive Diseases Research Core Center, Cleveland, OH, United States
- Germ-Free and Gut Microbiome Core, Digestive Health Research Institute, Case Western Reserve University, Cleveland, OH, United States
| | - Fabio Cominelli
- Division of Gastroenterology and Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, United States
- Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
- Mouse Models, Silvio O'Conte Cleveland Digestive Diseases Research Core Center, Cleveland, OH, United States
- Germ-Free and Gut Microbiome Core, Digestive Health Research Institute, Case Western Reserve University, Cleveland, OH, United States
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Pérez de Arce E, Quera R, Quigley EMM. The Dilemma of Persistent Irritable Bowel Syndrome Symptoms in Patients with Quiescent Inflammatory Bowel Disease. Gastroenterol Clin North Am 2021; 50:689-711. [PMID: 34304795 DOI: 10.1016/j.gtc.2021.03.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Irritable bowel syndrome and inflammatory bowel disease differ in their natural evolution, etiopathogenesis, diagnostic criteria, and therapeutic approach. However, recent evidence has suggested some similarities in mechanisms underlying symptom development and progression. There is a relevant role for alterations in the microbiome-brain-gut axis in both diseases. The presence of irritable bowel syndrome symptoms in patients with quiescent inflammatory bowel disease is common in clinical practice. To determine the cause of irritable bowel syndrome symptoms in patients with quiescent inflammatory bowel disease is a clinical challenge. This review aims to illustrate possible causes and solutions for these patients.
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Affiliation(s)
- Edith Pérez de Arce
- Department of Medicine, Division of Gastroenterology, Hospital Clínico Universidad de Chile, Dr. Carlos Lorca Tobar 999, Independencia, Región Metropolitana, Santiago, Chile
| | - Rodrigo Quera
- Division of Gastroenterology, Inflammatory Bowel Disease Program, Clínica Universidad de los Andes, Estoril 450, Las Condes, Región Metropolitana, Santiago, Chile
| | - Eamonn M M Quigley
- Division of Gastroenterology and Hepatology, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital, Weill Cornell Medical College, Houston, TX, USA.
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Affiliation(s)
- Jason K Hou
- Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, One Baylor Plaza, Houston, TX, 77030, USA. .,Department of Medicine, Section of Gastroenterology, Baylor College of Medicine, Houston, TX, USA.
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Small Intestinal Bacterial Overgrowth in Functional Dyspepsia: A Systematic Review and Meta-Analysis. Am J Gastroenterol 2021; 116:935-942. [PMID: 33734110 DOI: 10.14309/ajg.0000000000001197] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Accepted: 01/22/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION This systematic review and meta-analysis aimed to determine the role of small intestinal bacterial overgrowth (SIBO) in patients with functional dyspepsia (FD). METHODS Electronic databases were searched until July 2020 for studies reporting prevalence of SIBO in FD. The prevalence rates, odds ratio, and 95% confidence intervals (CIs) of SIBO in FD and controls were calculated. RESULTS Seven studies with 263 patients with FD and 84 controls were identified. The odds for SIBO in patients with FD were significantly higher as compared to that in controls (odds ratio = 4.3, 95% CI, 1.1-17.5, 4 studies, 234 participants); however, there was moderate heterogeneity in this analysis. Including high-quality, case-control studies (all using glucose breath tests [GBTs]), the risk of SIBO in patients with FD as compared to controls was 2.8 higher (95% CI 0.8-10.0, 3 studies, 200 participants) with minimal heterogeneity in this analysis. Using the lactulose breath test, SIBO prevalence in FD was significantly higher (53.4%, 95% CI 33.9-71.9, 3 studies, 110 participants) as compared to that with GBT (17.2%, 95% CI 8.6-31.6, 4 studies, 153 participants). Substantial heterogeneity was found in studies using the lactulose breath test but not in studies using GBT. There was no significant difference in SIBO prevalence in patients with FD according to FD subtype. DISCUSSION This meta-analysis suggests a link between FD and SIBO. The quality of evidence is low and can be largely attributed to the type of breath test for SIBO diagnosis and clinical heterogeneity. More appropriately designed studies are required to confirm the link between SIBO and FD.
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Holtmann G, Shah A, Morrison M. From trash to gold: gastrointestinal microbiome research in patients with functional gastrointestinal disorders. J Investig Med 2021. [DOI: 10.1136/jim-2021-001903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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