The commensal bacteria that colonize the gastrointestinal mucosa profoundly affect host physiological functions including metabolism, cellular proliferation, inflammation and immunity. These effects are driven by the ability of resident bacteria to produce small molecules and metabolites as well as to coordinate cross-talk with host immune cells both at the intestinal barrier and systemically. Many current cancer therapies rely on stimulation of antitumour immune responses, but whether the gut microbiota might influence host responses to cancer therapeutics via the immune system was largely unknown.
Compositional differences in the gut microbiota were associated with clinical responses to ICIs. Importantly, reconstituting germ-free mice with faecal transplants from non-responding patients blunts the antitumour effects of PD-1 blockade by restraining local and systemic immunity, thus suggesting that the composition of the gut microbiome might be one factor accounting for primary resistance to ICIs. Unexpectedly, across these studies, little overlap was found in the specific bacterial taxa or species correlating with successful response, thus prompting the researchers to speculate on the variables that might account for these differences, such as the techniques used to analyse patient samples, geographical diversity, and diet and lifestyle factors.
Confirmation that gut microbial communities are an influential force mediating responses to a range of therapeutic modalities has raised the intriguing possibility that microbe-based therapies could eventually be implemented in clinical settings. For example, manipulating the human gut microbiota could take the form of dietary interventions and prebiotic supplementation, faecal microbiota transplantations, and administration of bacterial consortia or probiotics. However, before these possibilities can come to fruition in treating patients, more work is needed to identify and validate reliable predictive microbiome biomarkers and to fundamentally define what truly constitutes a favourable microbiome that can drive effective cancer therapy responses.
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