Pharmacological Activation of Pyruvate Kinase M2 Inhibits CD4+ T Cell Pathogenicity and Suppresses Autoimmunity

Abstract

A multitude of diverse microorganisms, termed the microbiota, reside in the gut, respi-ratory tract, skin, and genital tract of humans and other animals. Recent advances inmetagenomic sequencing and bioinformatics have enabled detailed characterization ofthese vital microbial communities. Studies in animal models have uncovered vital previ-ously unrecognized roles for the microbiota in normal function of the immune responses,and when perturbed, in the pathogenesis of diseases of the gastrointestinal tract andlungs, but also at distant sites in the body including the brain. The composition of gutand respiratory microbiota can influence systemic inflammatory responses that medi-ate asthma, allergy, inflammatory bowel disease, obesity-related diseases, and neurode-velopmental or neurodegenerative conditions. Experiments in mouse models as wellas emerging clinical studies have revealed that therapeutic manipulation of the micro-biota, using fecal microbiota transplantation, probiotics, or engineered probiotics repre-sent effective nontoxic approaches for the treatment or prevention ofClostridium difficileinfection, allergy, and autoimmune diseases and may enhance the efficacy of certaincancer immunotherapeutics. This review discusses how commensal bacteria can influ-ence immune responses that mediate a range of human diseases and how the microbiotaare being targeted to treat these diseases, especially those resistant to pharmacologicaltherapies