Systematic review: the association between the gut microbiota and medical therapies in inflammatory bowel disease

• Published in: Alimentary pharmacology & therapeutics 2022-01, Vol.55 (1), p.26-48
• Main Authors: Radhakrishnan, Shiva T., Alexander, James L., Mullish, Benjamin H., Gallagher, Kate I., Powell, Nick, Hicks, Lucy C., Hart, Ailsa L., Li, Jia V., Marchesi, Julian R., Williams, Horace R. T.
• Format: Article
• Language: English
• Subjects: Escherichia; Faecalibacterium; Gastrointestinal Microbiome; Genera; Humans; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - drug therapy; Infliximab; Intestinal microflora; Intestine; Microbiota; Monoclonal antibodies; Mucosa; Patients; Phenotypes; Tumor Necrosis Factor Inhibitors; Tumor necrosis factor-α
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/apt.16656

Summary Background The gut microbiota has been implicated in the pathogenesis of inflammatory bowel disease (IBD), with Faecalibacterium prausnitizii associated with protection, and certain genera (including Shigella and Escherichia) associated with adverse features. The variability of patient response to medical therapies in IBD is incompletely understood. Given the recognised contribution of the microbiota to treatment efficacy in other conditions, there may be interplay between the gut microbiota, IBD medical therapy and IBD phenotype. Aims To evaluate the bidirectional relationship between IBD medical therapies and the gut microbiota. Methods We conducted a systematic search of MEDLINE and EMBASE. All original studies analysing interactions between the gut microbiota and established IBD medical therapies were included. Results We screened 1296 records; 19 studies were eligible. There was heterogeneity in terms of sample analysis, treatment protocols, and outcome reporting. Increased baseline α‐diversity was observed in responders versus non‐responders treated with exclusive enteral nutrition (EEN), infliximab, ustekinumab or vedolizumab. Higher baseline Faecalibacterium predicted response to infliximab and ustekinumab. A post‐treatment increase in Faecalibacterium prausnitzii was noted in responders to aminosalicylates, anti‐TNF medications and ustekinumab; conversely, this species decreased in responders to EEN. Escherichia was a consistent marker of unfavourable drug response, and its presence in the gut mucosa correlated with inflammation in aminosalicylate‐treated patients. Conclusions Both gut microbiota diversity and specific taxonomic features (including high abundance of Faecalibacterium) are associated with the efficacy of a range of IBD therapies. These findings hold promise for a potential role for the gut microbiota in explaining the heterogeneity of patient response to IBD treatments. In a systematic review of studies investigating associations between the gut microbiota and medical treatments for inflammatory bowel disease, increased alpha diversity and relative abundance of Faecalibacterium prausnitzii were markers of favourable outcomes, while increased relative abundance of Escherichia/Shigella was a consistent marker of unabated inflammation and treatment non‐response.