Following your gut: the emerging role of the gut microbiota in predicting and treating immune-related adverse events

Abstract

Purpose of review Although immune checkpoint inhibition has reshaped the therapeutic landscape leading to improved outcomes across an array of both solid and hematologic malignancies, a significant source of morbidity is caused by immune-related adverse events (irAEs) caused by these agents. Recent findings The gut microbiota has emerged as a biomarker of response to these agents, and more recently, also as a key determinant of development of irAEs. Emerging data have revealed that enrichment of certain bacterial genera is associated with an increased risk of irAEs, with the most robust evidence pointing to an intimate connection with the development of immune-related diarrhea and colitis. These bacteria include Bacteroides, Enterobacteriaceae, and Proteobacteria (such as Klebsiella and Proteus). Lachnospiraceae spp. and Streptococcus spp. have been implicated irAE-wide in the context of ipilimumab. Summary We review recent lines of evidence pointing to the role of baseline gut microbiota on the development of irAE, and the potentials for therapeutic manipulation of the gut microbiota in order to reduce irAE severity. The connections between gut microbiome signatures of response and toxicity will need to be untangled in further studies.