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      Interaction between drugs and the gut microbiome

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          Abstract

          The human gut microbiome is a complex ecosystem that can mediate the interaction of the human host with their environment. The interaction between gut microbes and commonly used non-antibiotic drugs is complex and bidirectional: gut microbiome composition can be influenced by drugs, but, vice versa, the gut microbiome can also influence an individual’s response to a drug by enzymatically transforming the drug’s structure and altering its bioavailability, bioactivity or toxicity (pharmacomicrobiomics). The gut microbiome can also indirectly impact an individual’s response to immunotherapy in cancer treatment. In this review we discuss the bidirectional interactions between microbes and drugs, describe the changes in gut microbiota induced by commonly used non-antibiotic drugs, and their potential clinical consequences and summarise how the microbiome impacts drug effectiveness and its role in immunotherapy. Understanding how the microbiome metabolises drugs and reduces treatment efficacy will unlock the possibility of modulating the gut microbiome to improve treatment.

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          Most cited references24

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          Microbiota-mediated colonization resistance against intestinal pathogens.

          Commensal bacteria inhabit mucosal and epidermal surfaces in mice and humans, and have effects on metabolic and immune pathways in their hosts. Recent studies indicate that the commensal microbiota can be manipulated to prevent and even to cure infections that are caused by pathogenic bacteria, particularly pathogens that are broadly resistant to antibiotics, such as vancomycin-resistant Enterococcus faecium, Gram-negative Enterobacteriaceae and Clostridium difficile. In this Review, we discuss how immune- mediated colonization resistance against antibiotic-resistant intestinal pathogens is influenced by the composition of the commensal microbiota. We also review recent advances characterizing the ability of different commensal bacterial families, genera and species to restore colonization resistance to intestinal pathogens in antibiotic-treated hosts.
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            Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab

            Ipilimumab, an immune checkpoint inhibitor targeting CTLA-4, prolongs survival in a subset of patients with metastatic melanoma (MM) but can induce immune-related adverse events, including enterocolitis. We hypothesized that baseline gut microbiota could predict ipilimumab anti-tumor response and/or intestinal toxicity.
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              A defined commensal consortium elicits CD8 T cells and anti-cancer immunity

              There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103+ dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.
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                Author and article information

                Journal
                Gut
                Gut
                gutjnl
                gut
                Gut
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0017-5749
                1468-3288
                August 2020
                14 May 2020
                : 69
                : 8
                : 1510-1519
                Affiliations
                [1 ] departmentDepartment of Gastroenterology and Hepatology , University of Groningen, University Medical Centre Groningen , Groningen, The Netherlands
                [2 ] departmentDepartment of Genetics , University of Groningen and University Medical Center Groningen , Groningen, The Netherlands
                [3 ] departmentDepartment of Pediatrics , University Medical Center Groningen , Groningen, The Netherlands
                Author notes
                [Correspondence to ] Dr Rinse K Weersma, Gastroenterology and Hepatology, University of Groningen, University Medical Centre Groningen, Groningen 9700 RB, The Netherlands; r.k.weersma@ 123456umcg.nl
                Author information
                http://orcid.org/0000-0001-7928-7371
                Article
                gutjnl-2019-320204
                10.1136/gutjnl-2019-320204
                7398478
                32409589
                62ff90df-3b9c-4232-ad02-d4bf9a897204
                © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:  https://creativecommons.org/licenses/by/4.0/.

                History
                : 30 March 2020
                : 21 April 2020
                : 28 April 2020
                Funding
                Funded by: NWO Gravitation Netherlands Organ-on-Chip Initiative;
                Award ID: 024.003.001
                Funded by: NWO Gravitation grant ExposomeNL;
                Funded by: FundRef http://dx.doi.org/10.13039/100004331, Johnson and Johnson;
                Funded by: FundRef http://dx.doi.org/10.13039/100008497, Boston Scientific Corporation;
                Funded by: FundRef http://dx.doi.org/10.13039/100006483, AbbVie;
                Funded by: Ferring and Tramedico;
                Funded by: FundRef http://dx.doi.org/10.13039/501100003246, Nederlandse Organisatie voor Wetenschappelijk Onderzoek;
                Award ID: 016.178.056
                Funded by: Seerave Foundation;
                Funded by: ERC starting grant;
                Funded by: MSD;
                Funded by: FundRef http://dx.doi.org/10.13039/501100002996, Hartstichting;
                Award ID: 2018-27
                Funded by: FundRef http://dx.doi.org/10.13039/501100008359, Maag Lever Darm Stichting;
                Award ID: 16-14
                Funded by: FundRef http://dx.doi.org/10.13039/100008373, Takeda Pharmaceutical Company;
                Categories
                Recent Advances in Basic Science
                1506
                2312
                1239
                Custom metadata
                unlocked

                Gastroenterology & Hepatology
                proton pump inhibition,immunotherapy,drug metabolism,intestinal microbiology

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