Drug-microbiota interactions and treatment response: Relevance to rheumatoid arthritis

Ellie Sayers; Alex MacGregor; Simon R. Carding; Ellie Sayers; Alex MacGregor; Simon R. Carding

doi:10.3934/microbiol.2018.4.642

AIMS Microbiology

2018, Volume 4, Issue 4: 642-654. doi: 10.3934/microbiol.2018.4.642

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Drug-microbiota interactions and treatment response: Relevance to rheumatoid arthritis

1.
Gut Health and Food Safety Programme, Quadram Institute Bioscience, Norwich, Norfolk, NR4 7UA, UK
2.
Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, Norfolk, NR4 7TJ, UK

Received: 20 August 2018 Accepted: 24 October 2018 Published: 26 October 2018

Knowledge about associations between changes in the structure and/or function of intestinal microbes (the microbiota) and the pathogenesis of various diseases is expanding. However, interactions between the intestinal microbiota and different pharmaceuticals and the impact of these on responses to treatment are less well studied. Several mechanisms are known by which drug-microbiota interactions can influence drug bioavailability, efficacy, and/or toxicity. This includes direct activation or inactivation of drugs by microbial enzymes which can enhance or reduce drug effectiveness. The extensive metabolic capabilities of the intestinal microbiota make it a hotspot for drug modification. However, drugs can also influence the microbiota profoundly and change the outcome of interactions with the host. Additionally, individual microbiota signatures are unique, leading to substantial variation in host responses to particular drugs. In this review, we describe several known and emerging examples of how drug-microbiota interactions influence the responses of patients to treatment for various diseases, including inflammatory bowel disease, type 2 diabetes and cancer. Focussing on rheumatoid arthritis (RA), a chronic inflammatory disease of the joints which has been linked with microbial dysbiosis, we propose mechanisms by which the intestinal microbiota may affect responses to treatment with methotrexate which are highly variable. Furthering our knowledge of this subject will eventually lead to the adoption of new treatment strategies incorporating microbiota signatures to predict or improve treatment outcomes.
- intestinal microbiota,
- metabolism,
- methotrexate,
- drug response
Citation: Ellie Sayers, Alex MacGregor, Simon R. Carding. Drug-microbiota interactions and treatment response: Relevance to rheumatoid arthritis[J]. AIMS Microbiology, 2018, 4(4): 642-654. doi: 10.3934/microbiol.2018.4.642

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Abstract

Knowledge about associations between changes in the structure and/or function of intestinal microbes (the microbiota) and the pathogenesis of various diseases is expanding. However, interactions between the intestinal microbiota and different pharmaceuticals and the impact of these on responses to treatment are less well studied. Several mechanisms are known by which drug-microbiota interactions can influence drug bioavailability, efficacy, and/or toxicity. This includes direct activation or inactivation of drugs by microbial enzymes which can enhance or reduce drug effectiveness. The extensive metabolic capabilities of the intestinal microbiota make it a hotspot for drug modification. However, drugs can also influence the microbiota profoundly and change the outcome of interactions with the host. Additionally, individual microbiota signatures are unique, leading to substantial variation in host responses to particular drugs. In this review, we describe several known and emerging examples of how drug-microbiota interactions influence the responses of patients to treatment for various diseases, including inflammatory bowel disease, type 2 diabetes and cancer. Focussing on rheumatoid arthritis (RA), a chronic inflammatory disease of the joints which has been linked with microbial dysbiosis, we propose mechanisms by which the intestinal microbiota may affect responses to treatment with methotrexate which are highly variable. Furthering our knowledge of this subject will eventually lead to the adoption of new treatment strategies incorporating microbiota signatures to predict or improve treatment outcomes.

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