Specific Gut Bacterium Linked to Irritable Bowel Syndrome

The incidence of Irritable Bowel Syndrome (IBS) steeply increases following a gastroenteritis episode, suggesting a possible causative role for microbial perturbation. Gut microbiota composition studies overwhelmingly rely on fecal material.

Fecal and mucus-associated bacteria represent distinctive populations, with the latter more likely to influence the epithelium. In particular, bacterial presence in the inner mucus layer might result in epithelial stress and immune activation. Analyses of fecal microbiota have not demonstrated consistent alterations in IBS.

Biomedical scientists at the University of Gothenburg (Gothenburg, Sweden) and their colleagues prospectively included 62 IBS patients and 31 normal controls that underwent sigmoidoscopy with sampling of biopsies in methanol-Carnoy for future histology/immunohistochemistry and real-time PCR analysis. In a randomly selected subset of participants (the first/explorative cohort, IBS n=22, healthy n=14), mucus was collected from ex vivo sigmoid colon biopsies and analyzed by mass spectrometry (MS).

Mucus samples were prepared for MS according to a modified version of the Filter-Aided Sample Preparation (FASP) protocol. Nano-liquid chromatography-tandem MS was performed on a Q-Exactive instrument (Thermo Fisher Scientific, Bremen, Germany). Histology and immunohistochemistry was performed on tissue sections. Sections were examined using an Eclipse E-1000 epifluorescent microscope (Nikon, Tokyo, Japan). All PCR reactions were carried out in triplicate, using a Bio-Rad CFX96 Real-Time System (Bio-Rad, Hercules., CA, USA).

The investigators reported that metaproteomic analysis of colon mucus samples identified peptides from potentially pathogenic Brachyspira species in a subset of patients with IBS. Using multiple diagnostic methods, mucosal Brachyspira colonization was detected in a total of 19/62 (31%) patients with IBS from two prospective cohorts, versus 0/31 healthy volunteers. The prevalence of Brachyspira colonization in IBS with diarrhea (IBS-D) was 40% in both cohorts. Brachyspira attachment to the colonocyte apical membrane was observed in 20% of patients with IBS and associated with accelerated oro-anal transit, mild mucosal inflammation, mast cell activation and alterations of molecular pathways linked to bacterial uptake and ion–fluid homeostasis. According to species discrimination by real-time PCR, 50% of patients with spirochetosis were colonized by B. pilosicoli; others had either B. aalborgi or the closely related, unconfirmed, species B. hominis.

Magnus Simrén, MD, PhD, a Professor of Gastroenterology, and a co-author of the study, said, “The study suggests that the bacterium may be found in about a third of individuals with IBS. We want to see whether this can be confirmed in a larger study, and we're also going to investigate whether, and how, Brachyspira causes symptoms in IBS. Our findings may open up completely new opportunities for treating and perhaps even curing some IBS patients, especially those who have diarrhea.”

The authors concluded that mucosal Brachyspira colonization was significantly more common in IBS and associated with distinctive clinical, histological and molecular characteristics. The observations suggest a role for Brachyspira in the pathogenesis of IBS, particularly IBS-D. The study was published on November 11, 2020 in the journal GUT.

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