Influence of immunomodulatory drugs on the gut microbiota

Immunomodulatory medications are a mainstay of treatment for autoimmune diseases and malignancies. In addition to their direct effects on immune cells, these medications also impact the gut microbiota. Drug-induced shifts in commensal microbes can lead to indirect but important changes in the immune response. We performed a comprehensive literature search focusing on immunotherapy/microbe interactions. Immunotherapies were categorized into 5 subtypes based on their mechanisms of action: cell trafficking inhibitors, immune checkpoint inhibitors, immunomodulators, antiproliferative drugs, and inflammatory cytokine inhibitors. Although no consistent relationships were observed between types of immunotherapy and microbiota, most immunotherapies were associated with shifts in specific colonizing bacterial taxa. The relationships between colonizing microbes and drug efficacy were not well-studied for autoimmune diseases. In contrast, the efficacy of immune checkpoint inhibitors for cancer was tied to the baseline composition of the gut microbiota. There was a paucity of high-quality data; existing data were generated using heterogeneous sampling and analytic techniques, and most studies involved small numbers of participants. Further work is needed to elucidate the extent and clinical significance of immunotherapy effects on the human microbiome (Translational Research 2021; 233:144-161) Abbreviations: CD = cluster of differentiation; Th = helper T cells; Treg = regulatory T-cell subsets; GALT = gut-associated lymphoid tissue; TLR2 = Toll-like receptor-2; MMF = Mycophenolate mofetil; MTX = Methotrexate; RA = Rheumatoid Arthritis; MS = Multiple Sclerosis; MLGs = microbial linkage groups; ALZ = Alemtuzumab; CTLA-4 = cytotoxic T-lymphocyte-associated protein 4; PD-1 = programmed cell death protein 1; PD-L1 = programmed cell death protein 1 ligand 1; PD-L2 = programmed cell death protein 1 ligand 2; ICIs = Immune checkpoint inhibitors; NTZ = Natalizumab; LPS = lipopolysaccharide; DMF = Dimethyl fumarate; GA = Glatiramer acetate; IFNb = Interferon beta; TNFi's = TNF inhibitors; TNFa = tumor necrosis factor alpha; IgA = immu