Abstract
The gut microbiome affects many aspects of human health including aging and cancer. Recent evidence has demonstrated a causal relationship between the microbes in the gut and response to cancer treatment with immune checkpoint inhibitors (ICIs). Individuals whose cancer responds to ICIs can be distinguished from those who do not solely by the composition of their gut microbes at the start of treatment. Provocatively, preclinical models supplemented with a single microbial strain or microbially-derived metabolite can modify response to treatment. The microbiome therefore represents both a biomarker and therapeutic target for modifying and improving cancer care. However, as is often the case with emerging treatments, older adults are not strongly represented in the clinical trials leading to treatment approval. There are known shifts in the microbiome as one ages. The mechanism by which these shifts occur with age are important to consider considering efforts to modify the microbiome to promote response. Here we summarize the literature on the microbes related to aging and interpret them in the context of those associated with response to ICIs. We demonstrate that these age-related changes tend to shift the microbiome toward a non-responder-like composition, lacking microbes demonstrated to support treatment response, which may contribute to the decreased efficacy in this population. We review the potential mechanisms by which these effects occur and posit a model to interpret the broad-level changes observed. Finally, we discuss trials currently underway to target this novel treatment modality in the understudied and growing older adult population.