The influence of biologics on the microbiome in immune-mediated inflammatory diseases: A systematic review

Immune-mediated inflammatory diseases (IMIDs) are a group of several chronic disorders with elusive pathogenesis that results in dysregulation of the normal immune response and leads to organ-specific or systemic inflammation. There are many reports on gastrointestinal or skin dysbiosis in patients with IMIDs; however, it is not clear whether dysbiosis is a cause or a result of the observed inflammation. We aimed to determine whether treatment of IMIDs patients with biologics affects their microbiota in comparison with baseline or placebo.

We searched for studies in MEDLINE, Embase, Scopus, and Web of Science. Due to both high heterogeneity and lacking data, vote-counting and structured tables were used to summarize the data.

A total of 25 longitudinal human studies with 816 IMIDs patients receiving biologics were included. Data on α-diversity change are inconclusive. Most evidence supports the increase in all α-diversity metrics in responding inflammatory bowel disease (IBD) patients; however, vote counting did not confirm the significance of the directional change. In case of β-diversity, treatment with biologics made patients' microbiome more similar to the microbiome of healthy controls in 5 out of 7 studies. The changes in taxa abundance and predicted functionality of microbiome were systematically summarized. Limited number and quality of the included studies highly restricted the conclusions of the study.

Local inflammation may play pivotal role in the gut microbiome disruption in IMIDs patients. The effect of the biologics on human microbiota should be evaluated in randomized controlled trials and transparently reported.