The total gut mucosal and fecal bacterial load increases in successful treatment of inflammatory bowel disease with infliximab

TL;DR

This study shows that successful infliximab treatment for inflammatory bowel disease increases gut bacteria levels, especially beneficial butyrate-producing bacteria, in fecal samples of responders.

Contribution

The study reveals that successful infliximab treatment increases gut bacterial load and shifts microbiota composition in IBD responders.

Findings

Responders to infliximab showed increased total bacterial load in ileum and fecal samples during treatment.

The increase in bacterial load was driven by butyrate-producing Firmicutes in fecal samples of responders.

Non-responders did not show similar changes in bacterial composition during treatment.

Abstract

Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory gastrointestinal disorders linked to genetic predisposition and environmental factors. The gut microbiota, composed of various microorganisms, plays a crucial role in IBD, as reduced anaerobic bacteria and short-chain fatty acid (SCFA) producers are associated with predisposition to IBD. There is no cure for IBD, but the treatment aims for mucosal healing including conventional treatment and biological therapies such as infliximab (IFX). IFX, a tumor necrosis factor alpha (TNF-α) blocker, effectively reduces inflammation, but around 50% of patients do not achieve long-term remission. Fecal samples were collected from 70 patients with IBD (24 CD, 44 UC, and 2 IBDU), and mucosal samples were collected from both ileum and colon from 63 patients before, during, and after IFX treatment. The bacterial microbiota composition was investigated by targeting the conserved 16S region in MiSeq sequencing. Additionally, the relative sequencing data were quantified by qPCR. Responders to IFX had an increase in the total bacterial load in ileum and fecal samples during treatment, primarily driven by butyrate-producing bacteria in the Firmicutes phylum. Interestingly, this was only observed in the fecal samples in responders, but not non-responders to IFX. These results indicate that the gut bacterial microbiota of responders to IFX is changing toward a more favorable composition during successful IFX treatment.

The research described in this paper enhances our understanding of how infliximab (IFX) treatment affects the gut mucosal and fecal microbiota in patients with inflammatory bowel disease (IBD). Using 16S sequencing technique and quantification by qPCR, the study revealed that successful treatment with IFX led to an increase in the total bacterial load in both ileal and fecal samples, as well as a shift in bacterial composition toward a more favorable profile with an increase in butyrate-producing bacteria in the fecal samples in responders but not in non-responders to infliximab. This study emphasizes that the gut microbiota plays an important role in the healing process during infliximab treatment in IBD.

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