Microbiota-derived metabolites as drivers of gut-brain communication

Gut Microbes. 2022 Jan-Dec;14(1):2102878. doi: 10.1080/19490976.2022.2102878.


Alterations in the gut microbiota composition have been associated with a range of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. The gut microbes transform and metabolize dietary- and host-derived molecules generating a diverse group of metabolites with local and systemic effects. The bi-directional communication between brain and the microbes residing in the gut, the so-called gut-brain axis, consists of a network of immunological, neuronal, and endocrine signaling pathways. Although the full variety of mechanisms of the gut-brain crosstalk is yet to be established, the existing data demonstrates that a single metabolite or its derivatives are likely among the key inductors within the gut-brain axis communication. However, more research is needed to understand the molecular mechanisms underlying how gut microbiota associated metabolites alter brain functions, and to examine if different interventional approaches targeting the gut microbiota could be used in prevention and treatment of neurological disorders, as reviewed herein.Abbreviations:4-EPS 4-ethylphenylsulfate; 5-AVA(B) 5-aminovaleric acid (betaine); Aβ Amyloid beta protein; AhR Aryl hydrocarbon receptor; ASD Autism spectrum disorder; BBB Blood-brain barrier; BDNF Brain-derived neurotrophic factor; CNS Central nervous system; GABA ɣ-aminobutyric acid; GF Germ-free; MIA Maternal immune activation; SCFA Short-chain fatty acid; 3M-4-TMAB 3-methyl-4-(trimethylammonio)butanoate; 4-TMAP 4-(trimethylammonio)pentanoate; TMA(O) Trimethylamine(-N-oxide); TUDCA Tauroursodeoxycholic acid; ZO Zonula occludens proteins.

Keywords: Gut microbiota; gut-brain axis; metabolism; metabolites; short-chain fatty acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / metabolism
  • Autism Spectrum Disorder* / metabolism
  • Brain / metabolism
  • Fatty Acids, Volatile / metabolism
  • Gastrointestinal Microbiome* / physiology
  • Humans


  • Amyloid beta-Peptides
  • Fatty Acids, Volatile

Grants and funding

This work was supported by the ERA-NET NEURON 2019 Translational Biomarkers Grant no 334814 ”Gut2Behave”, by the Fonds de la Recherce Scientifique (FRD-FNRS) in Belgium (PINT-MULTI R.8013.19, NEURON, call 2019) and PDR T.0068.19 attributed to ND. KH has received support from Academy of Finland (Grant no 321716) and European Union's Horizon 2020 research and innovation programme under Marie Sklodowska-Curie (Grant no 754412. SL has received support from Chaire d'excellence Région Nouvelle Aquitaine ExoMarquAge (135059720-13062120); The Foundation for Medical Research (FRM, DEQ20170336724) and the Institut National pour la Recherche Agronomique, l'Alimentation et l'Environnement.