Alterations in gut microbiome composition and function in irritable bowel syndrome and increased probiotic abundance with daily supplementation

AbstractBackgroundIrritable bowel syndrome (IBS) is characterized by abdominal discomfort and irregular bowel movements and stool consistency. Because there are different symptoms associated with IBS, it is difficult to diagnose the role of the microbiome in IBS.ObjectiveHere, we present a study that includes metagenomic sequencing of stool samples from subjects with the predominant subtypes of IBS and a healthy cohort. We collected longitudinal samples from individuals with IBS who took daily made-to-order precision probiotic and prebiotic supplementation throughout the study.Materials and MethodsThis study includes a population of 489 individuals with IBS and 122 healthy controls. All stool samples were subjected to shotgun metagenomic sequencing. Precision probiotics and prebiotics were formulated for all subjects with longitudinal timepoints.ResultsThere was significant variation explained in the microbiome between the healthy and IBS cohorts. Individuals with IBS had a lower gut microbiome diversity and reduced anti-inflammatory microbes compared to the healthy controls. Eubacterium rectale and Faecalibacterium prausnitzii were associated with healthy microbiomes while Shigella species were associated with IBS. Pathway analysis indicated a functional imbalance of short chain fatty acids, vitamins, and a microbial component of Gram-negative bacteria in IBS compared to healthy controls. In the longitudinal dataset, there was a significant difference in microbiome composition between timepoints 1 and 3. There was also a significant increase in the overall microbiome score and relative abundances of probiotic species used to target the symptoms associated with IBS.ConclusionsWe identified microbes and pathways that differentiate healthy and IBS microbiomes. In response to precision probiotic supplementation, we identified a significant improvement in the overall microbiome score in individuals with IBS. These results suggest an important role for probiotics in managing IBS symptoms and modulation of the microbiome as a potential management strategy.ImportanceAn estimated 35 million people in the United States and 11.5% of the population globally are affected by IBS. Immunity, genetics, environment, diet, small intestinal bacterial overgrowth (SIBO), and the gut microbiome are all factors that contribute to the onset or triggers of IBS. With strong supporting evidence that the gut microbiome may influence symptoms associated with IBS, elucidating the important microbes that contribute to the symptoms and severity is important to make decisions for targeted treatment. As probiotics have become more common in treating IBS symptoms, identifying effective probiotics may help inform future studies and treatment.

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IMAGINE Network’s Mind And Gut Interactions Cohort (MAGIC) Study: a protocol for a prospective observational multicentre cohort study in inflammatory bowel disease and irritable bowel syndrome

BMJ Open ◽

10.1136/bmjopen-2020-041733 ◽

2020 ◽

Vol 10 (10) ◽

pp. e041733

Author(s):

Paul Moayyedi ◽

Glenda MacQueen ◽

Charles N Bernstein ◽

Stephen Vanner ◽

Premysl Bercik ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Irritable Bowel Syndrome ◽

Cohort Study ◽

Bowel Disease ◽

Gut Microbiome ◽

Psychological Status ◽

Healthy Controls ◽

Gi Symptoms ◽

Inflammatory Bowel ◽

Irritable Bowel

IntroductionGut microbiome and diet may be important in irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and comorbid psychiatric conditions, but the mechanisms are unclear. We will create a large cohort of patients with IBS, IBD and healthy controls, and follow them over time, collecting dietary and mental health information and biological samples, to assess their gastrointestinal (GI) and psychological symptoms in association with their diet, gut microbiome and metabolome.Methods and analysisThis 5-year observational prospective cohort study is recruiting 8000 participants from 15 Canadian centres. Persons with IBS who are 13 years of age and older or IBD ≥5 years will be recruited. Healthy controls will be recruited from the general public and from friends or relatives of those with IBD or IBS who do not have GI symptoms. Participants answer surveys and provide blood, urine and stool samples annually. Surveys assess disease activity, quality of life, physical pain, lifestyle factors, psychological status and diet. The main outcomes evaluated will be the association between the diet, inflammatory, genetic, microbiome and metabolomic profiles in those with IBD and IBS compared with healthy controls using multivariate logistic regression. We will also compare these profiles in those with active versus quiescent disease and those with and without psychological comorbidity.Ethics and disseminationApproval has been obtained from the institutional review boards of all centres taking part in the study. We will develop evidence-based knowledge translation initiatives for patients, clinicians and policymakers to disseminate results to relevant stakeholders.Trial registration number:NCT03131414

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Increased Expression of Toll-Like Receptors 4, 5, and 9 in Small Bowel Mucosa from Patients with Irritable Bowel Syndrome

BioMed Research International ◽

10.1155/2017/9624702 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 12

Author(s):

Aldona Dlugosz ◽

Katherina Zakikhany ◽

Nathalie Acevedo ◽

Mauro D’Amato ◽

Greger Lindberg

Keyword(s):

Irritable Bowel Syndrome ◽

Small Bowel ◽

Mrna Levels ◽

Healthy Controls ◽

Toll Like Receptors ◽

Commensal Flora ◽

Significant Difference ◽

Small Bowel Mucosa ◽

Irritable Bowel ◽

Bowel Mucosa

The aim of our study was to compare patients with irritable bowel syndrome (IBS) and healthy controls regarding the expression of toll-like receptors 2, 4, 5, and 9 (TLR2, TLR4, TLR5, and TLR9), the primary mucosal receptors of bacterial components, in small and large bowel mucosa.Methods.We analysed biopsies from jejunum and sigmoid colon of 22 patients (17 females) with IBS aged 18–66 (median: 39) years and 14 healthy volunteers (12 females) aged 22–61 (median: 42) years. Eight patients had constipation-predominant IBS (C-IBS), 7 had diarrhoea-predominant IBS (D-IBS), and 7 had IBS without predominance of constipation or diarrhoea. We analysed mRNA levels for TLRs using quantitative PCR and distribution of TLRs in mucosa using immunohistochemistry.Results.We found increased mRNA expression of TLR4 (mean fold change1.85±0.31versus1.0±0.20;p<0.05), TLR5 (1.96±0.36versus1.0±0.20;p<0.05) and TLR9 (2.00±0.24versus1.0±0.25;p<0.01) but not of TLR2 in the small bowel mucosa from patients with IBS compared to the controls. There was no significant difference in mRNA levels for TLRs in colon mucosa between patients and controls.Conclusion.Upregulation of TLR4, TLR5, and TLR9 suggests the involvement of bacteria or dysregulation of the immune response to commensal flora in small bowel mucosa in IBS patients.

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Gut Microbiome and Its Role in the Pathophysiology of Irritable Bowel Syndrome

Acta gastroenterológica latinoamericana ◽

10.52787/dxfc9250 ◽

2021 ◽

Vol 51 (4) ◽

Author(s):

Giada De Palma ◽

Premysl Bercik

Keyword(s):

Irritable Bowel Syndrome ◽

Abdominal Pain ◽

Gut Microbiota ◽

Gut Microbiome ◽

Gastrointestinal Disorder ◽

Healthy Controls ◽

Fecal Microbiome ◽

Targeted Treatments ◽

Irritable Bowel ◽

And Function

Irritable bowel syndrome is the most common functional gastrointestinal disorder, affecting up to 9% individuals globally. Although the etiology of this syndrome is likely heterogenous, it presents with its hallmark symptoms of abdominal pain and altered intestinal motility. Moreover, it is considered to be a disorder of the gut-brain interaction, and the microbiome has often been implicated as a central player in its pathophysiology. Patients with irritable bowel syndrome display altered composition and function of the gut microbiota compared to healthy controls. Microbiome directed therapies, such as probiotics, antibiotics and fecal microbiome transplantation, appear to be beneficial for both gut symptoms and psychiatric comorbidities. This review aims to recapitulate the available literature on the microbiome contribution to the pathophysiology and symptoms presentation of irritable bowel syndrome, as well as the current literature on microbiome-targeted treatments for this disease.

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Entamoeba species associated with chronic diarrhoea in Pakistan

Epidemiology and Infection ◽

10.1017/s0950268811000215 ◽

2011 ◽

Vol 140 (2) ◽

pp. 323-328 ◽

Cited By ~ 13

Author(s):

J. YAKOOB ◽

Z. ABBAS ◽

M. A. BEG ◽

S. NAZ ◽

R. KHAN ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Irritable Bowel Syndrome ◽

Abdominal Pain ◽

Chronic Diarrhoea ◽

Healthy Controls ◽

Chain Reaction ◽

Stool Samples ◽

Polymerase Chain ◽

Irritable Bowel

SUMMARYWe determined the prevalence of Entamoeba (E.) histolytica, E. dispar and E. moshkovskii in patients with chronic diarrhoea associated with abdominal pain or discomfort mimicking irritable bowel syndrome. Stool samples were collected from 161 patients with chronic diarrhoea and from 157 healthy controls. Stool microscopy with modified trichrome stain, culture and polymerase chain reaction (PCR) for Entamoeba spp. differentiation was performed. Microscopy demonstrated Entamoeba cysts in 44% (57/129) of patients with diarrhoea compared to 29% (44/151) of controls (P=0·009). In patients with diarrhoea, PCR for E. histolytica was positive in 9% (11/129) (P=0·008), E. dispar in 19% (24/129) (P=0·117) and E. moshkovskii in 19% (24/129) (P<0·001). E. histolytica and E. moshkovskii were significantly associated with diarrhoea while E. dispar was found equally in both groups.

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A Comprehensive Self-Management Program With Diet Education Does Not Alter Microbiome Characteristics in Women With Irritable Bowel Syndrome

Biological Research For Nursing ◽

10.1177/1099800420984543 ◽

2021 ◽

pp. 109980042098454

Author(s):

Kendra J. Kamp ◽

Anna M. Plantinga ◽

Kevin C. Cain ◽

Robert L. Burr ◽

Pamela Barney ◽

...

Keyword(s):

Quality Of Life ◽

Irritable Bowel Syndrome ◽

Usual Care ◽

Gut Microbiome ◽

Beta Diversity ◽

Self Management ◽

Symptom Improvement ◽

Microbiome Composition ◽

Irritable Bowel

Background and Purpose: Changes in diet and lifestyle factors are frequently recommended for persons with irritable bowel syndrome (IBS). It is unknown whether these recommendations alter the gut microbiome and/or whether baseline microbiome predicts improvement in symptoms and quality of life following treatment. Therefore, the purpose of this study was to explore if baseline gut microbiome composition predicted response to a Comprehensive Self-Management (CSM) intervention and if the intervention resulted in a different gut microbiome composition compared to usual care. Methods: Individuals aged 18–70 years with IBS symptoms ≥6 months were recruited using convenience sampling. Individuals were excluded if medication use or comorbidities would influence symptoms or microbiome. Participants completed a baseline assessment and were randomized into the eight-session CSM intervention which included dietary education and cognitive behavioral therapy versus usual care. Questionnaires included demographics, quality of life, and symptom diaries. Fecal samples were collected at baseline and 3-month post-randomization for 16S rRNA-based microbiome analysis. Results: Within the CSM intervention group (n = 30), Shannon diversity, richness, and beta diversity measures at baseline did not predict benefit from the CSM intervention at 3 months, as measured by change in abdominal pain and quality of life. Based on both alpha and beta diversity, the change from baseline to follow-up microbiome bacterial taxa did not differ between CSM (n = 25) and usual care (n = 25). Conclusions and Inferences: Baseline microbiome does not predict symptom improvement with CSM intervention. We do not find evidence that the CSM intervention influences gut microbiome diversity or composition over the course of 3 months.

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Does Fibre-fix provided to people with irritable bowel syndrome who are consuming a low FODMAP diet improve their gut health, gut microbiome, sleep and mental health? A double-blinded, randomised controlled trial

BMJ Open Gastroenterology ◽

10.1136/bmjgast-2020-000448 ◽

2020 ◽

Vol 7 (1) ◽

pp. e000448

Author(s):

Ran Yan ◽

Mandy Murphy ◽

Angela Genoni ◽

Evania Marlow ◽

Ian C Dunican ◽

...

Keyword(s):

Mental Health ◽

Irritable Bowel Syndrome ◽

Gut Microbiome ◽

Controlled Study ◽

Gut Health ◽

Management Options ◽

Microbiome Composition ◽

Bowel Symptoms ◽

Irritable Bowel ◽

Fodmap Diet

IntroductionA diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) is an effective way to reduce gut symptoms in people with irritable bowel syndrome (IBS). This diet reduces the intake of fermentable fibres, leading to changes of the gut microbiota and insufficient fermentation in the large bowel, resulting in reduced production of short-chain fatty acids (SCFAs), such as butyrate, which has unfavourable implications for gut health, sleep and mental health. This study will examine the effect of Fibre-fix, a supplement containing a mix of dietary fibres, on the human gut microbiome composition, fermentative capacity, sleep, quality of life (QOL) and mental health of people with IBS who consume a low FODMAP diet (LFD).Methods and analysisA randomised, double-blind, placebo-controlled, study design is proposed to examine whether Fibre-fix added to an existing LFD may help modulate gastrointestinal function, improve markers of sleep, mental health and promote QOL in patients with IBS. Participants will provide stool and blood samples, daily bowel symptoms diaries and 3-day diet records. Additionally, they will complete validated questionnaires relating to FODMAP intake, sleep, mental health and QOL before and after a 3-week intervention. Gut health will be assessed via faecal microbiome composition, faecal pH and SCFA levels. Alteration of sleep will be recorded using an actigraphy device worn by all participants over the whole study. Multivariate analysis will be used to examine the gut microbiome and repeated measures Analysis of variance (ANOVA) will be used for dependent variables from questionnaires related to bowel symptoms, stool type, sleep, mental health and QOL to assess the differences between intervention and control groups after adjustment for confounding variables.Ethics and disseminationEthics approval was obtained from the Human Research Ethics Committee of Edith Cowan University (2019-00619-YAN). Results will be disseminated in peer-review journal publications, and conference presentations. Participants will be provided with a summary of findings once the study is completed. If Fibre-fix is shown to result in favourable changes in gut microbial composition, SCFA production, sleep and mental well-being without exacerbating symptoms, this will provide additional dietary management options for those with IBS following an LFD.Trial registration numberACTRN12620000032954.

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The level and prevalence of depression and anxiety among patients with different subtypes of irritable bowel syndrome: a network meta-analysis

BMC Gastroenterology ◽

10.1186/s12876-020-01593-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhichao Hu ◽

Meixuan Li ◽

Liang Yao ◽

Yinshu Wang ◽

Enkang Wang ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Meta Analysis ◽

Cochrane Library ◽

Anxiety And Depression ◽

Healthy Controls ◽

Depression And Anxiety ◽

Significant Difference ◽

Prevalence Of Depression ◽

The Difference ◽

Irritable Bowel

Abstract Background Irritable bowel syndrome (IBS) is a very common functional bowel disorder. However, the difference of depression and anxiety comorbidities among different IBS subtypes is still not well evaluated. This study aims to investigate the difference in the level and prevalence of depression and anxiety among healthy controls and patients with different subtypes of IBS. Methods PubMed, EMBASE and the Cochrane library were searched systematically until August 17, 2020. Studies that investigated depression and/or anxiety levels or prevalence among different IBS-subtype patients measured at baseline or the same point were included. Network meta-analysis was conducted to analyze standardized mean difference (SMD) of anxiety and depression levels, and single arm meta-analysis was performed for prevalence of anxiety and depression among different IBS subtypes. Results Eighteen studies involving 7095 participants were included. Network meta-analyses results showed healthy controls had a lower level of depression than IBS with mixed symptoms of constipation and diarrhea (IBS-M) [SMD = − 1.57; 95% confidence interval (CI) − 2.21, − 0.92], IBS with constipation (IBS-C) (SMD = − 1.53; 95% CI − 2.13, − 0.93) and IBS with diarrhea (IBS-D)(SMD = − 1.41; 95% CI − 1.97, − 0.85), while no significant difference was found between IBS unclassified (IBS-U) and healthy controls (SMD = − 0.58; 95% CI − 2.15, 1.00). There was also no significant difference in the level of depression among different IBS subtypes patients. The results of anxiety were similar to depression. Ranking probability showed that IBS-M was associated with the highest level of depression and anxiety symptoms, followed by IBS-C/IBS-D and IBS-U. Single-arm meta-analysis showed IBS-C had the highest prevalence of depression (38%) and anxiety (40%), followed by IBS-D, IBS-M and IBS-U. Conclusion The results indicated that IBS-M was more likely to be associated with a higher level of depression and anxiety, and the prevalence of depression and anxiety in IBS-C was highest. The psychological screening and appropriate psychotherapy are needed for patients with IBS-C, IBS-D and IBS-M instead of IBS-U.

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Probiotic VSL#3 Treatment Reduces Colonic Permeability and Abdominal Pain Symptoms in Patients With Irritable Bowel Syndrome

Frontiers in Pain Research ◽

10.3389/fpain.2021.691689 ◽

2021 ◽

Vol 2 ◽

Author(s):

Prapaporn Boonma ◽

Jordan M. Shapiro ◽

Emily B. Hollister ◽

Shyam Badu ◽

Qinglong Wu ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Abdominal Pain ◽

Treatment Duration ◽

Sequencing Analysis ◽

Metagenomic Sequencing ◽

Gut Permeability ◽

Microbiome Composition ◽

Study Completion ◽

Irritable Bowel ◽

Pain Symptoms

Background: Little is known regarding the clinical impact of treatment and treatment duration of probiotic VSL#3 on gut and microbiome function in irritable bowel syndrome (IBS). As part of a safety trial, we assessed the effect of VSL#3 treatment duration on abdominal pain, stooling, gut permeability, microbiome composition and function.Methods: Adults with IBS were randomized into an open label trial to receive the probiotic VSL#3 for 4 or 8 weeks. Adverse events, abdominal pain, and stooling patterns were recorded daily. Gut permeability, fecal bile acid levels, and microbiome composition were profiled at baseline and after treatment.Results: Fifteen subjects completed the trial (4-week: n = 8; 8-week: n = 7). Number of pain episodes decreased in both groups (P = 0.049 and P = 0.034; 4- vs. 8-week, respectively). Probiotic organisms contained in VSL#3 were detected in feces by whole shotgun metagenomic sequencing analysis and relative abundances of Streptococcus thermophilus, Bifidobacterium animalis, Lactobacillus plantarum, and Lactobacillus casei subsp. paraccasei correlated significantly with improved abdominal pain symptoms and colonic permeability at study completion. Although abdominal pain correlated significantly with the detection of probiotic species at study completion, a composite view of gut microbiome structure showed no changes in community diversity or composition after VSL#3 treatment.Conclusions: Probiotic organisms identified in stool correlated significantly with improvement in colonic permeability and clinical symptoms, prompting future studies to investigate the mechanistic role of VSL#3 and colonic permeability in IBS pathophysiology in a larger randomized controlled trial.Clinical Trial Registration:www.clinicaltrials.gov, Identifier: NCT00971711.

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Shotgun metagenomics reveals an enrichment of potentially cross-reactive bacterial epitopes in ankylosing spondylitis patients, as well as the effects of TNFi therapy upon microbiome composition

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2019-215763 ◽

2019 ◽

Vol 79 (1) ◽

pp. 132-140 ◽

Cited By ~ 16

Author(s):

Jian Yin ◽

Peter Richard Sternes ◽

Mingbang Wang ◽

Jing Song ◽

Mark Morrison ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Gut Microbiome ◽

Bacterial Species ◽

Metagenomic Sequencing ◽

Healthy Controls ◽

Hla B27 ◽

Clinical Genetic ◽

Shotgun Metagenomics ◽

Microbiome Composition ◽

Shotgun Metagenomic Sequencing

ObjectivesDiverse evidence including clinical, genetic and microbiome studies support a major role of the gut microbiome in the common immune-mediated arthropathy, ankylosing spondylitis (AS). We set out to (1) further define the key microbial characteristics driving disease, and (2) examine the effects of tumour necrosis factor-inhibitor (TNFi) therapy upon the microbiome.MethodsThe stools from a case–control cohort of 250 Han-Chinese subjects underwent shotgun metagenomic sequencing. All subjects were genotyped using the Illumina CoreExome SNP microarray.ResultsPrevious reports of gut dysbiosis in AS were reconfirmed and several notable bacterial species and functional categories were differentially abundant. TNFi therapy was correlated with a restoration the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. Enrichment of bacterial peptides homologous to HLA-B27-presented epitopes was observed in the stools of patients with AS, suggesting that either HLA-B27 fails to clear these or that they are involved in driving HLA-B27-associated immune reactions. TNFi therapy largely restored the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. TNFi therapy of patients with AS was also associated with a reduction of potentially arthritogenic bacterial peptides, relative to untreated patients.ConclusionThese findings emphasise the key role that the gut microbiome plays in driving the pathogenesis of AS and highlight potential therapeutic and/or preventative targets.

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