Introduction Studies have suggested that in addition to antimicrobials, some non‐antibiotics may alter the gut microbiome. This systematic review sought to determine if there is an association between immunosuppressive agents used in recipients of solid organ transplants (SOT) and alterations in the gut microbiome. Methods English language PubMed and Scopus searches were conducted to identify relevant articles. Inclusion criteria were defined as pertaining to solid organ transplantation, immunosuppression, and the gut microbiome. Articles were excluded if they contained only genetic microbiota descriptions, narrative reviews of bacteria, or described bacteria as a pathogen for infections. PRISMA reporting was used to guide this literature review. Results A preliminary search identified 665 articles, of which 75 articles met the inclusion criteria, and 10 articles remained after application of exclusion criteria. Seventy‐one percent of articles discussed calcineurin inhibitors, such as tacrolimus, 38% included mycophenolate mofetil, and 52% included steroids, such as prednisone. Some studies utilized a combination of immunosuppressants or had multiple study arms. Seventy percent of the articles indicated changes in quantities of anaerobic bacteria including Ruminococcaceae, Lachnospiraceae, Firmicutes, Bacteroides, and Clostridiales. Combinations of immunosuppressant agents were associated with an increase in colonization of Escherichia coli and Enterococcus sp. Conclusion Some immunosuppressants are associated with changes in gut flora, but the impact on clinical outcomes is unknown. Robust clinical trials delineating the direct effect of immunosuppressants on the gut microbiome as well as the impact on clinical outcomes are warranted.

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