The Influence of Microbial Metabolites in the Gastrointestinal Microenvironment on Anticancer Immunity

Abstract

The gastrointestinal (GI) tumour microenvironment is characterised by its unique colonisation with bacteria that are estimated to match the total number of cells in our body. It is becoming increasingly clear that the microbiome and its metabolites are important orchestrators of local and systemic immune responses, anticancer immunity and the host response to cancer therapy. Apart from their role as an energy source, metabolites have been shown to modulate inflammation, immune cell function and cancer cell survival. The polarisation of immune cell subsets by microbial metabolites towards either pro-or antitumorigenic functions strongly affects cancer progression and outcomes. In this chapter, we will discuss the link between microbial metabolites in the GI tumour microenvironment, anticancer immune responses and cancer progression.

The Human Microbiome in Relation to Cancer Risk: A Systematic Review of Epidemiologic Studies

“…Another example is the important role of indole derivatives, produced by gut bacteria from the degradation of tryptophan, such as aryl hydrocarbon receptor ligands, to maintain intestinal homeostasis, limit inflammation and thus, indirectly reduce the risk of colorectal, prostate and breast cancer (127)(128)(129). Finally, short-chain fatty acids are produced by the gut microbiome through fermentation of nondigestible fiber and starch and help maintain balance between intestinal immunity and inflammation (130,131). As such, microbiota may influence the risk of many cancers, independent of anatomic location due to effects of microbial metabolites on inflammation, an important hallmark of cancer, and other metabolic conditions associated with cancer risk.…”

Tissue-wide metabolomics reveals wide impact of gut microbiota on mice metabolite composition

“…Many of these metabolites are taken up into host circulation and eventually into various tissues to participate in endogenous metabolism. Notably, the effect of microbial compounds within the mammalian host environment varies from one tissue to another based on the type and metabolic status of affected tissues [40][41][42]. Metabolomics is a well-established and powerful tool that can be applied to identify microbiomederived or microbiome-modified metabolites and to better understand the modulation of microbiota and how it affects the metabolism in a host [43,44].…”

Tissue-wide Metabolomics Reveals Wide Impact of Gut Microbiota on Mice Metabolite Composition

“…Many of these metabolites are taken up into host circulation and eventually into various tissues to participate in endogenous metabolism. Notably, the effect of microbial compounds within the mammalian host environment varies from one tissue to another based on the type and metabolic status of affected tissues [40][41][42]. Metabolomics is a well-established and powerful tool that can be applied to identify microbiome-derived or microbiome-modi ed metabolites and to better understand the modulation of microbiota and how it affects the metabolism in a host [43,44].…”