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Mol Neurobiol. 2017 Aug;54(6):4432-4451. doi: 10.1007/s12035-016-0004-2. Epub 2016 Jun 27.

The Role of the Microbial Metabolites Including Tryptophan Catabolites and Short Chain Fatty Acids in the Pathophysiology of Immune-Inflammatory and Neuroimmune Disease.

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Tir Na Nog, Bryn Road seaside 87, Llanelli, SA152LW, Wales, UK.
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.
Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, 60430-040, Brazil.
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.
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.
Centre for Molecular and Medical Research, School of Medicine, Deakin University, Geelong, Australia.
IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, P.O. Box 291, Geelong, VIC, 3220, Australia.
Health Sciences Postgraduate Program, Health Sciences Center, State University of Londrina, Londrina, Parana, Brazil.


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.


Autism; Bacterial translocation; Diabetes type 2; Immune inflammation; Leaky gut; Oxidative stress

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