Neuromodulatory effects and targets of the SCFAs and gasotransmitters produced by the human symbiotic microbiota

• Published in: Microbial ecology in health and disease Vol. 27; no. 1; pp. 30971 - 12
• Main Authors: Oleskin, Alexander V., Shenderov, Boris A.
• Format: Journal Article
• Language: English
• Published: Sweden Taylor & Francis 2016; Taylor & Francis Ltd; Co-Action Publishing
• Subjects: Amino acids; Ammonia; Autism; Bacteroides; Behavior; Biological activity; Brain; Carbon monoxide; Chemical synthesis; Digestive system; Epigenetics; Fatty acids; Fermentation; gasotransmitters; Gastrointestinal tract; Homeostasis; Hormones; Human subjects; Hydrogen; hydrogen sulfide; Hypotheses; Immunology; Immunomodulation; Intestinal microflora; Intestine; Ion channels; Lipid metabolism; Low molecular weights; Mammals; Medical research; Metabolism; Metabolites; microbiome; Microbiota; Microorganisms; Mitochondria; Modulators; Molecular modelling; Molecular weight; neuromediator; Neuromodulation; neurotransmitter; nitric oxide; Organs; Pathogenesis; Physiological effects; Physiology; Post-translation; Probiotics; Protein turnover; Review; Rodents; short-chain fatty acids; Signaling; Transcription factors; Transmitters; nitric oxide; gasotransmitters; hydrogen sulfide; neuromediator; ammonia; carbon monoxide; neurotransmitter; short-chain fatty acids; microbiome
• DOI: 10.3402/mehd.v27.30971
• ISSN: 1651-2235; 0891-060X

The symbiotic gut microbiota plays an important role in the development and homeostasis of the host organism. Its physiological, biochemical, behavioral, and communicative effects are mediated by multiple low molecular weight compounds. Recent data on small molecules produced by gut microbiota in mammalian organisms demonstrate the paramount importance of these biologically active molecules in terms of biology and medicine. Many of these molecules are pleiotropic mediators exerting effects on various tissues and organs. This review is focused on the functional roles of gaseous molecules that perform neuromediator and/or endocrine functions. The molecular mechanisms that underlie the effects of microbial fermentation-derived gaseous metabolites are not well understood. It is possible that these metabolites produce their effects via immunological, biochemical, and neuroendocrine mechanisms that involve endogenous and microbial modulators and transmitters; of considerable importance are also changes in epigenetic transcriptional factors, protein post-translational modification, lipid and mitochondrial metabolism, redox signaling, and ion channel/gap junction/transporter regulation. Recent findings have revealed that interactivity among such modulators/transmitters is a prerequisite for the ongoing dialog between microbial cells and host cells, including neurons. Using simple reliable methods for the detection and measurement of short-chain fatty acids (SCFAs) and small gaseous molecules in eukaryotic tissues and prokaryotic cells, selective inhibitors of enzymes that participate in their synthesis, as well as safe chemical and microbial donors of pleiotropic mediators and modulators of host intestinal microbial ecology, should enable us to apply these chemicals as novel therapeutics and medical research tools.