Research Highlights Intestinal Dysbiosis as Defining Feature of Microscopic Colitis
Key findings
- Research demonstrated changes in diversity and dysbiosis during the active versus remission phases of microscopic colitis, and in patients with active microscopic colitis versus controls
- A bacterium previously reported to have anti-inflammatory properties was significantly less abundant in patients with active microscopic colitis than in those with functional diarrhea or those whose colitis was in remission
- The relative abundance of several metabolic pathways, including those involved in glucose biosynthesis and adaptation to oxidative stress, were decreased in patients with active microscopic colitis
Several years ago, Swedish gastroenterologists reported the case of a woman with intractable microscopic colitis who required a temporary ileostomy and had colonic biopsies analyzed before, during and after fecal stream diversion. The resolution of mucosal inflammation was noted with fecal diversion, and they found that restoration of the fecal stream was associated with recurrence of the disease. Their observations suggest the gut microbiome has a critical role in microscopic colitis.
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Recently, Hamed Khalili, MD, PhD, gastroenterologist at Massachusetts General Hospital, and colleagues built on that research by characterizing the composition and function of the gut microbiome in microscopic colitis. Their findings are published in Clinical Gastroenterology and Hepatology.
Study Participants
Researchers sequenced the microbiome of stool samples from 60 patients:
- 20 patients during the active and remission phases of microscopic colitis (80% female, average age 63)
- 20 age- and sex-matched healthy controls
- 20 patients with functional diarrhea (65% female, average age 62)
The active phase of microscopic colitis was defined as at least three bowel movements per day and a Bristol score ≥5. The researchers calculated a microbial dysbiosis index as the log of [the total abundance of organisms increased] divided by [the total abundance of organisms decreased].
Diversity of the Microbiome
Researchers discovered that, in patients with colitis, there was a significant difference in alpha diversity (the number of different species represented) between the active and remission phases.
Alpha diversity was lower in patients with active colitis than in healthy controls or patients with functional diarrhea, although the differences were not statistically significant.
The microbial dysbiosis index was significantly higher in patients with active colitis than in healthy controls, patients with functional diarrhea or those whose colitis was in remission.
Growth Dynamics of the Microbiome
The researchers explored whether disease status was more strongly linked to the growth dynamics of the gut microbiome than to the diversity of species. They estimated the peak-to-trough ratio (PTR), a measure of species' growth rates.
- Compared to healthy controls, patients with active colitis showed significant increases in the global PTR and the Alistipes finegoldii–specific PTR
- There were no significant differences in PTRs when patients with active colitis were compared to those with functional diarrhea or those whose colitis was in remission
Alistipes species are butyrate-producing bacteria that demonstrated anti-inflammatory properties in a mouse model of colitis and are depleted in pediatric patients with new-onset inflammatory disease.
Composition of the Microbiome
Alistipes putredinis was significantly less abundant in patients with colitis than in healthy controls or patients with functional diarrhea.
Haemophilus parainfluenzae, Veillonella parvula and Veillonella unclassified species were significantly more abundant in patients with colitis than in healthy controls.
There were no significant differences at the species level when patients with active colitis were compared with those whose colitis was in remission.
Functional Profiling
The gluconeogenesis I pathway (involved in glucose synthesis) and the inosine-5-phosphate biosynthesis III pathway (involved in adaptation to oxidative stress) were decreased in patients with active colitis compared to healthy controls.
Researchers also found that degradation of purine deoxyribonucleoside was increased in patients with active colitis compared to healthy controls.
They conclude that, similar to the case of inflammatory bowel disease, dysbiosis is the defining feature of the gut microbiome in patients with microscopic colitis.
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