Small talk: microbial metabolites involved in the signaling from microbiota to brain.

Giorgia Caspani, Jonathan Swann

Journal: Current opinion in pharmacology 2020;48():99-106

PMID: 31525562

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Plain Language Summary

The ‪gut-brain axis (GBA) is the communication network‪ between the gastrointestinal tract and the central nervous system. An array of gut bacteria-derived metabolites mediates this interaction between the gastrointestinal system and the brain, influencing ‪physiological and pathological processes in direct and indirect ‪ways. Thus a variation in the gut microbiome can alter the functional ‪capacity and output of the gut-brain-communication. In this review, the authors summarise key bacterial metabolites from the gut and their effect on the brain. Addressed are short-chain fatty acids, their impact on gut and brain barrier integrity, their role in appetite regulation, and their association with anxiety and depressive disorders amongst other aspects. Secondly, bile acids, which are processed by the microbiome, can activate several receptors. And thus divergence gut bacteria can alter the composition of bile acids and change their signalling capacity. Bile acids can also directly modify gut and blood-brain barrier function and may carry a signalling role in the brain. A few neurotransmitters are covered in this article, as several types of gut bacteria ‪synthesize neurotransmitters, such as serotonin and dopamine. Though, it is uncertain whether all gut-derived neurotransmitters can reach the brain. However, certain GABA-producing bacteria have been shown to elicit higher GABA levels in the brain. The microbiota can also be involved with the conversion of neurotransmitters such as dopamine. The final section briefly capture the evidence of other brain health-relevant molecules derived from the intestinal ‪microbiota, including Lipopolysaccharides, choline, lactate and B-Vitamins. This review yields a short and comprehensive summary highlighting the many ways the gut can influence brain function and health and could be of interest to those providing mental health support in light of gut function.

Abstract

The wealth of biotransformational capabilities encoded in the microbiome expose the host to an array of bioactive xenobiotic products. Several of these metabolites participate in the communication between the gastrointestinal tract and the central nervous system and have potential to modulate central physiological and pathological processes. This biochemical interplay can occur through various direct and indirect mechanisms. These include binding to host receptors in the brain, stimulation of the vagus nerve in the gut, alteration of central neurotransmission, and modulation of neuroinflammation. Here, the potential for short chain fatty acids, bile acids, neurotransmitters and other bioactive products of the microbiome to participate in the gut-brain axis will be reviewed.

Address: Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, UK.; Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, UK. Electronic address: [email protected].

DOI: 10.1016/j.coph.2019.08.001