Current evidence and clinical relevance of drug-microbiota interactions in inflammatory bowel disease

Abstract

BackgroundInflammatory bowel disease (IBD) is a chronic relapsing-remitting disease. An adverse immune reaction toward the intestinal microbiota is involved in the pathophysiology and microbial perturbations are associated with IBD in general and with flares specifically. Although medical drugs are the cornerstone of current treatment, responses vary widely between patients and drugs. The intestinal microbiota can metabolize medical drugs, which may influence IBD drug (non-)response and side effects. Conversely, several drugs can impact the intestinal microbiota and thereby host effects. This review provides a comprehensive overview of current evidence on bidirectional interactions between the microbiota and relevant IBD drugs (pharmacomicrobiomics).MethodsElectronic literature searches were conducted in PubMed, Web of Science and Cochrane databases to identify relevant publications. Studies reporting on microbiota composition and/or drug metabolism were included.ResultsThe intestinal microbiota can both enzymatically activate IBD pro-drugs (e.g., in case of thiopurines), but also inactivate certain drugs (e.g., mesalazine by acetylation via N-acetyltransferase 1 and infliximab via IgG-degrading enzymes). Aminosalicylates, corticosteroids, thiopurines, calcineurin inhibitors, anti-tumor necrosis factor biologicals and tofacitinib were all reported to alter the intestinal microbiota composition, including changes in microbial diversity and/or relative abundances of various microbial taxa.ConclusionVarious lines of evidence have shown the ability of the intestinal microbiota to interfere with IBD drugs and vice versa. These interactions can influence treatment response, but well-designed clinical studies and combined in vivo and ex vivo models are needed to achieve consistent findings and evaluate clinical relevance.

Recent steroid use and the relapse risk in ulcerative colitis patients with endoscopic healing

“…It has been reported that patients with UC have a different gut microbiota 27 and that steroid use may affect the gut microbiota in patients with inflammatory bowel disease. 28 An interaction between gut microbiota and the immune system has also been reported. 29,30 For example, maintaining remission after steroid administration may change the gut microbiota to a composition that is less likely to relapse.…”

“…These factors may include gut microbiota and immune dysregulation. It has been reported that patients with UC have a different gut microbiota 27 and that steroid use may affect the gut microbiota in patients with inflammatory bowel disease 28 . An interaction between gut microbiota and the immune system has also been reported 29,30 .…”

Drug-microbiota interactions: an emerging priority for precision medicine

“…The digestive system is one of the most extensive areas of pharmacomicrobiomics because it is home to complicated and varied microbiota that is critical in drug metabolism and efficacy. 189 , 389 Gut microbiota has also been demonstrated to impact outcomes of drugs used to treat a variety of digestive diseases, e.g., inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS). 390 Patients with IBD have been detected to have altered gut microbiota composition and function, which may affect IVDR.…”

“…Recently, the research of drug-microbiota interactions has become a systematically developed field, due to the increasing fascination with the variation of gut microbiota. 62,[186][187][188][189] This field has given rise to various sub-disciplines, including pharmacomicrobiomics, pharmacometabonomics, and pharmacometagenomics. 159,[190][191][192][193] These sub-disciplines aim to study the effect of microbiota on PK and PD, and to explore how microbiota variation affects IVDR in human diseases [194][195][196][197] (Fig.…”

Exploring substrate–microbe interactions: a metabiotic approach toward developing targeted synbiotic compositions

“… 17 Colon-targeting of thiopurines may, therefore, be applied specifically in IBD to minimize the side effects of systemic thiopurine treatment, as previously proposed. 18 Colon-targeting per se has been achieved through the use of indigestible fibers (such as resistant-starch, pectin, chitosan, chondroitin, dextran, or guar gum) applied as coating materials that are degraded by gut bacteria. 19 …”