P110 STEROID-RESISTANCE AND STEROID-DEPENDENCE IN INFLAMMATORY BOWEL DISEASE CAN BE LINKED WITH GUT MICROBIOTA COMPOSITION CHANGES

Changes in the gut microbiota have been associated with two of the most common gastrointestinal diseases, inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Here, we performed a case-control analysis using shotgun metagenomic sequencing of stool samples from 1792 individuals with IBD and IBS compared with control individuals in the general population. Despite substantial overlap between the gut microbiome of patients with IBD and IBS compared with control individuals, we were able to use gut microbiota composition differences to distinguish patients with IBD from those with IBS. By combining species-level profiles and strain-level profiles with bacterial growth rates, metabolic functions, antibiotic resistance, and virulence factor analyses, we identified key bacterial species that may be involved in two common gastrointestinal diseases.

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Dysbiosis of gut microbiota in inflammatory bowel disease: Current therapies and potential for microbiota-modulating therapeutic approaches

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2020.5016 ◽

2020 ◽

Author(s):

Dikhnah Alshehri ◽

Omar Saadah ◽

Mahmoud Mosli ◽

Sherif Edris ◽

Rashad Alhindi ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Gut Microbiota ◽

Bowel Disease ◽

Current Treatment ◽

Intestinal Microbiome ◽

Microbiota Composition ◽

Therapeutic Approaches ◽

New Therapeutic Approaches ◽

Inflammatory Bowel ◽

Gut Microbiota Composition

There is a growing body of evidence reinforcing the unique connections between the host microbiome, health and diseases. Due to the extreme importance of the symbiotic relationship between the intestinal microbiome and the host, it is not surprising that any alteration in the gut microbiota would result in various diseases, including inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC). IBD is a chronic, relapsing-remitting condition that is associated with significant morbidity, mortality, compromised quality of life and costly medical care. Dysbiosis is believed to exacerbate the progression of IBD. One of the currently used treatments for IBD are anti-tumor necrosis factor (TNF) drugs, representing a biologic therapy that is reported to have an impact on the gut microbiota composition. The efficacy of anti-TNF agents is hindered by the possibility of non-response, which occurs in 10-20% of treated patients, and secondary loss of response, which occurs in up to 30% of treated patients. This underscores the need for novel therapies and studies that evaluate the role of the gut microbiota in these conditions. The success of any therapeutic strategy for IBD depends on our understanding of the interactions that occur between the gut microbiota and the host. In this review, the health and disease IBD-associated microbiota patterns will be discussed, in addition to the effect of currently used therapies for IBD on the gut microbiota composition, as well as new therapeutic approaches that can be used to overcome the current treatment constraints.

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Faculty Opinions recommendation of Gut microbiota composition and functional changes in inflammatory bowel disease and irritable bowel syndrome.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734657732.793573436 ◽

2020 ◽

Author(s):

Gwo-Tzer Ho ◽

Rahul Kalla

Keyword(s):

Inflammatory Bowel Disease ◽

Irritable Bowel Syndrome ◽

Gut Microbiota ◽

Bowel Disease ◽

Microbiota Composition ◽

Functional Changes ◽

Inflammatory Bowel ◽

Irritable Bowel ◽

Gut Microbiota Composition

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Transplantation of fecal microbiota from patients with inflammatory bowel disease and depression alters immune response and behavior in recipient mice

Scientific Reports ◽

10.1038/s41598-021-00088-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hyo-Min Jang ◽

Jeon-Kyung Kim ◽

Min-Kyung Joo ◽

Yoon-Jung Shin ◽

Chang Kyun Lee ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Gut Microbiota ◽

Cell Population ◽

Bowel Disease ◽

Fecal Microbiota ◽

Cell Populations ◽

Microbiota Composition ◽

Gut Dysbiosis ◽

Inflammatory Bowel ◽

Anxiety Depression

AbstractGut dysbiosis is closely associated with the occurrence of inflammatory bowel disease (IBD) and psychiatric disorder. Here, to understand the difference of gut microbiota composition and physiological effect between IBD patients with (IBD/D+) or without depression (IBD/D−), we analyzed the fecal microbiota composition of patients with IBD with (/D+) or without depression (/D−) and healthy volunteers (HVs) and examined the effects of these fecal microbiota transplantations (FMTs) on the occurrence of systemic inflammation and anxiety/depression in mice. FMTs from patients with IBD/D+ or IBD/D− caused IBD-like colitis in the transplanted mice: they increased the myeloperoxidase activity, IL-1β and IL-6 expression, and NF-κB+/CD11c+ cell population in the colon. Transplantation of the IBD/D+ patient feces (IBD/D+-F) caused IBD-like colitis more strongly than that of IBD/D−-F. FMTs from patients with IBD/D+ also caused anxiety-/depression-like behaviors, increased the NF-κB+/Iba1+ and lipopolysaccharide (LPS)+/Iba1+ cell populations, and decreased the BDNF+/NeuN+ cell population in the hippocampus. They increased LPS levels in the blood. FMTs from patients with IBD/D− caused anxiety-like, but not depression-like, behaviors. α-/β-diversities and composition of gut microbiota in IBD-F were different from those of HV feces (HV-F). The Enterobacteriaceae and Enterococcaceae populations and LPS levels were higher in the IBD-F than in the HV-F. The Enterococcaceae population was higher in IBD/D+-F vs. IBD/D−-F. However, the transplantation of HV-F into mice previously transplanted with IBD/D+-F significantly reduced depression-like behaviors, NF-κB+/Iba1+ and LPS+/Iba1+ cell populations in the hippocampus, LPS levels in the feces and blood, and IL-1β expression in the colon. These findings suggest that the outbreak of depression/anxiety may be dependent on the systemic inflammation with a leaky gut through the gut dysbiosis-attributable overproduction of bacterial LPS and suppression of tight junction protein expression in patients with IBD.

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DOP71 Fungal and bacterial gut microbiota in paediatric onset Inflammatory Bowel Disease introduced to infliximab

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab073.110 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S105-S105

Author(s):

R Ventin-Holmberg ◽

M Höyhtyä ◽

S Saqib ◽

K Korpela ◽

A Nikkonen ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Gut Microbiota ◽

Treatment Initiation ◽

Microbiota Composition ◽

Miseq Sequencing ◽

Sequencing Data ◽

Bacterial Microbiota ◽

Tnf Α ◽

Inflammatory Bowel ◽

Gut Microbiota Composition

Abstract Background Paediatric Inflammatory Bowel Disease (PIBD), including Crohn’s Disease (CD), Ulcerative Colitis (UC) and IBD undefined (IBDU) is increasing worldwide and is characterized by an onset inflammation in the gastrointestinal tract. The patients may present severe symptoms such as abdominal pain, diarrhoea and bloody stool. No defined pathogenesis has been established for PIBD, but an imbalanced intestinal microbiota is strongly associated to the disease. Anti-tumour necrosis factor alpha (TNF-α) is an effective drug to treat inflammation in IBD, but up to half of the patients do not have a long-term response to the drug. Presently, there are no methods available to predict the TNF-α response. Here we have investigated the biomarkers of the gut fungal and bacterial microbiota, which are largely unexplored in paediatric patients, particularly for the fungal microbiota, with the aim to find possible predictors of drug response. Methods The gut microbiota composition of 30 PIBD (25 CD, 2 UC and 3 IBDU) patients at the Children′s Hospital, University of Helsinki receiving the anti-TNF-α drug infliximab (IFX) was studied by MiSeq sequencing targeting the bacterial 16S rRNA gene and fungal ITS region separately from faecal samples collected before the start of treatment and two and six weeks after treatment initiation. The response to IFX was evaluated by a faecal calprotectin value below 100 µg/g at week six after treatment initiation. The fungal MiSeq sequencing data was processed by using the DADA2 pipeline, annotated to the BLAST database and analysed using the package mare. The bacterial MiSeq sequencing data was analysed using mare and annotated to the SILVA database. Results Both the fungal and bacterial microbiota differed significantly between responders compared to non-responders to IFX, further validated by high predictive power (area under curve > 0.8) for therapy response. This difference was characterized by an increase in short-chain fatty acid producing bacteria, such as bacteria in the class Clostridia in the responders at baseline. This was observed as elevated Faecalibacterium and Subdoligranulum genera in particular of responders at baseline. Additionally, Candida was increased while Saccharomyces was decreased in non-responders at the end of the study. Finally, we observed that the interkingdom correlations differed between response groups to IFX. Conclusion Our results strengthen the proposal that the gut microbiota composition of PIBD patients could predict the response to anti-TNF-α treatment in the future.

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