title: The Role of the Microbial Metabolites Including Tryptophan Catabolites and Short Chain Fatty Acids in the Pathophysiology of Immune-Inflammatory and Neuroimmune Disease.
abstract: There is a growing awareness that gut commensal metabolites play a major role in host physiology and indeed the pathophysiology of several illnesses. The composition of the microbiota largely determines the levels of tryptophan in the systemic circulation and hence, indirectly, the levels of serotonin in the brain. Some microbiota synthesize neurotransmitters directly, e.g., gamma-amino butyric acid, while modulating the synthesis of neurotransmitters, such as dopamine and norepinephrine, and brain-derived neurotropic factor (BDNF). The composition of the microbiota determines the levels and nature of tryptophan catabolites (TRYCATs) which in turn has profound effects on aryl hydrocarbon receptors, thereby influencing epithelial barrier integrity and the presence of an inflammatory or tolerogenic environment in the intestine and beyond. The composition of the microbiota also determines the levels and ratios of short chain fatty acids (SCFAs) such as butyrate and propionate. Butyrate is a key energy source for colonocytes. Dysbiosis leading to reduced levels of SCFAs, notably butyrate, therefore may have adverse effects on epithelial barrier integrity, energy homeostasis, and the T helper 17/regulatory/T cell balance. Moreover, dysbiosis leading to reduced butyrate levels may increase bacterial translocation into the systemic circulation. As examples, we describe the role of microbial metabolites in the pathophysiology of diabetes type 2 and autism.
authors.affiliation: Tir Na Nog, Bryn Road seaside 87, Llanelli, SA152LW, Wales, UK.
authors.forename: Gerwyn
authors.identifier: 0000-0002-2914-1128
authors.initials: G
authors.lastname: Morris
authors.affiliation: IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, P.O. Box 291, Geelong, VIC, 3220, Australia.|Orygen Youth Health Research Centre and the Centre of Youth Mental Health, The Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, University of Melbourne, Parkville, 3052, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.affiliation: Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, 60430-040, Brazil.
authors.forename: Andre
authors.initials: A
authors.lastname: Carvalho
authors.affiliation: Department of Pharmacology, School of Medicine, University Complutense of Madrid, Avda. Complutense s/n, 28040, Madrid, Spain.|Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Avda. Complutense s/n, 28040, Madrid, Spain.|Instituto de Investigación Hospital 12 de Octubre (Imas12), Avda. Complutense s/n, 28040, Madrid, Spain.
authors.forename: Javier R
authors.initials: JR
authors.lastname: Caso
authors.affiliation: Microbial Ecology, Nutrition & Health Research Unit, Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), Av. Agustin Escardino 7, 46980, Paterna, Valencia, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Sanz
authors.affiliation: Centre for Molecular and Medical Research, School of Medicine, Deakin University, Geelong, Australia.
authors.forename: Ken
authors.initials: K
authors.lastname: Walder
authors.affiliation: IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, P.O. Box 291, Geelong, VIC, 3220, Australia. dr.michaelmaes@hotmail.com.|Health Sciences Postgraduate Program, Health Sciences Center, State University of Londrina, Londrina, Parana, Brazil. dr.michaelmaes@hotmail.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
mesh_terms: D000818:Animals; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000382:microbiology*; D055442:Metabolome; D064307:Microbiota; D015213:Neuroimmunomodulation; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D005232:Fatty Acids, Volatile; D014364:Tryptophan
keywords: Autism; Bacterial translocation; Diabetes type 2; Immune inflammation; Leaky gut; Oxidative stress