Gut microbiome–based therapeutics in inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD), including both ulcerative colitis and Crohn's disease, is a chronic inflammatory disease of the gastrointestinal tract that is thought to arise from a combination of environmental, genetic and immunological factors. The gut microbiome, a diverse ecosystem of microorganisms residing in the digestive tract, has been proposed to play a role in the pathogenesis of IBD. There is an unmet clinical need for microbiome‐based therapies. This review will discuss the landscape of microbiome‐based therapeutics in IBD. Microbiome‐targeted therapeutics, such as antibiotics, pre‐/probiotics and faecal microbiota transplant (FMT), are based on the premise that restoring a healthy gut microbiome can attenuate mucosal inflammation. Antibiotics work directly to impede growth or eradicate specific gut microorganisms. Antibiotics may play a role in inducing clinical remission and treating refractory pouchitis and may be associated with immunogenicity to anti‐TNF biologics in IBD. Prebiotics are the molecular metabolic building blocks for commensal gut bacteria. Probiotics artificially introduce gut microorganisms thought to be beneficial to the local microenvironment and maybe be associated with symptom relief in IBD. FMT similarly introduces bacteria found in higher proportions of healthy persons, though in a more direct manner than probiotics. FMT has been associated with increased rates of clinical remission in IBD, but heterogeneity in FMT response may be influenced by IBD subtype, FMT donor selection and delivery protocols. Current evidence suggests that microbiome‐targeted therapeutics may have some benefit for IBD. Several studies are underway exploring the targeting of specific gut microbes or microbial pathways as therapy in IBD.