Changes in Gut Microbiome Associated With Biologic Therapy in Inflammatory Bowel Disease

Consistent changes in gut microbiome composition were identified in patients with inflammatory bowel diseases (IBD) who responded to treatment with biologic agents, according to a new systematic review published in Clinical Gastroenterology and Hepatology.

The investigators carried out a systematic review to study changes in microbiomes of fecal or colon samples from patients with IBD receiving treatment with biologic agents and to determine whether any microbiome changes (microbiome diversity, relative abundance, and microbial metabolic pathways) correlate with clinical outcomes (response, remission, and relapse), which would indicate utility as biomarkers of response to therapy.

In February 2019, 3 electronic databases were searched for studies that included the terms “(microbiome or microbiota) AND (biologic therapy OR anti-TNF OR infliximab OR adalimumab OR golimumab OR vedolizumab OR certolizumab OR ustekinumab OR natalizumab) AND (inflammatory bowel disease OR Crohn’s Disease OR Ulcerative Colitis)”.

The researchers followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines and the Cochrane Collaboration Guidelines for Systemic Reviews. Of the investigators, 2 independently used the Critical Appraisal Skills Programme (CASP) checklist to evaluate the methodologic quality of the included studies.

After excluding duplicates and studies that did not match the inclusion criteria, 10 studies were identified for review. All were prospective studies (9 original articles and 1 abstract) published between 2014 and 2018. These studies (7 on adults and 3 on children) included a total of 354 patients with IBD who had received biologic therapies and whose gut microbiomes were assessed.

Most of the studies (7/10) focused on patients with Crohn disease (CD); only 1 study focused on patients with ulcerative colitis (UC), and 2 studies included patients with either CD or UC. In terms of biologic therapy, the majority (8/10) of studies used an anti-tumor necrosis factor alpha agent (4 with infliximab, 1 with adalimumab, and 3 with both drugs); 1 study each used antibodies targeting integrins and interleukins.

Of the 10 studies, the investigators identified 2 common trends in the microbiomes of fecal or colon samples from patients receiving treatment with biologic agents. First, the relative abundance of Escherichia and Enterococcus bacteria decrease, whereas the relative abundances of short-chain fatty acid-producing bacteria increase. Second, higher microbial diversity at baseline or throughout treatment was associated with response to therapy.

Study limitations included, but were not limited to, variation in monoclonal antibodies used in studies; selection bias; varying practices for collection and processing of samples; technical aspects; variation in taxonomic classification; effect of confounding variables; and the low availability of quantitative data, which limited the potential use of meta-analysis.

The investigators concluded, “Prospective studies are needed to determine what changes are significantly associated with treatment, whether these changes are causes or effects of response, or whether the composition of the intestinal microbiome can be used to select treatments for patients with IBD.”

Reference

Estevinho MM, Rocha C, Correia L, et al. Features of fecal and colon microbiomes associate with responses to biologic therapies for inflammatory bowel diseases: a systematic review. Clin Gastroenterol Hepatol. 2019;0(0). doi:10.1016/j.cgh.2019.08.063