Exploration of the link between gut microbiota and purinergic signalling

Abstract

Growing evidence reveals that microorganisms in the gut are linked to metabolic health and disease risk in human beings to a considerable extent. The focus of research at this stage must tend to focus on cause-and-effect studies. In addition to being a component of DNA and RNA, purine metabolites can be involved in purine signalling in the body as chemical messengers. Abnormalities in purinergic signalling may lead to neuropathy, rheumatic immune diseases, inflammation, tumors, and a wide range of other diseases. It has proved that gut microbes are involved in purinergic signalling. The relationship between these gut-derived purinergic signalling molecules and host metabolism may be one of the important clues to our understanding of the mechanisms by which the microbiota affects host metabolism.

Keywords: A2A receptors; Gastrointestinal microbiome; Inosine; P2X receptors; Purinergic signalling.

Fig. 1

The release of eATP from the gut microbiota can induce apoptosis of Tfh cells and regulate IgA release by binding to P2X7 receptors on Tfh cells in Peyer’s patches (PPs). Also, the intestinal commensal SFB can induce the differentiation of Th17 and Tfh and stimulate the release of IgA with other cytokines. When the intestinal environment is stable, IgA produced in PPs can play a protective role in the intestinal environment. In contrast, once the homeostasis of the intestinal environment gets disrupted, SFB induces a strong autoimmune response. Inosine (INO), which is metabolized by some microorganisms in the gut, can act as a purinergic signalling factor binding to A2AR on the surface of CD4⁺ T cells, inhibiting the differentiation of helper T cells to play a Treg-like role. However, in a tumor environment or the presence of other inflammatory factors infiltration, the inosine-A2AR axis can play the opposite role and promote T cell differentiation