The role of the microbial metabolites including tryptophan catabolites and short chain fatty acids in the pathophysiology of immune-inflammatory and neuroimmunue disease. Morris, Gerwyn, Berk, Michael, Carvalho, Andre, Caso, Javier R, Sanz, Yolanda, Walder, Ken and Maes, Michael 2016, The role of the microbial metabolites including tryptophan catabolites and short chain fatty acids in the pathophysiology of immune-inflammatory and neuroimmunue disease., Molecular neurobiology, In press, pp. 1-20, doi: 10.1007/s12035-016-0004-2. Attached Files Name Description MIMEType Size Downloads Title The role of the microbial metabolites including tryptophan catabolites and short chain fatty acids in the pathophysiology of immune-inflammatory and neuroimmunue disease. Author(s) Morris, Gerwyn Berk, Michael orcid.org/0000-0002-5554-6946 Carvalho, Andre Caso, Javier R Sanz, Yolanda Walder, Ken orcid.org/0000-0002-6758-4763 Maes, Michael Journal name Molecular neurobiology Season In press Start page 1 End page 20 Total pages 20 Publisher Springer Place of publication Berlin, Germany Publication date 2016 ISSN 1559-1182 Keyword(s) Autism Bacterial translocation Diabetes type 2 Immune inflammation Leaky gut Oxidative stress Summary 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. Language eng DOI 10.1007/s12035-016-0004-2 Field of Research 1109 Neurosciences 1702 Cognitive Science Socio Economic Objective 929999 Health not elsewhere classified HERDC Research category C1 Refereed article in a scholarly journal ERA Research output type C Journal article Copyright notice ©2016, Springer Persistent URL http://hdl.handle.net/10536/DRO/DU:30085220 Document type: Journal Article Collections: Faculty of Health School of Medicine Related Links Link Description Connect to published version Go to link with your DU access privileges   Connect to Elements publication management system Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Versions Version Filter Type Wed, 03 Aug 2016, 14:25:06 EST Thu, 04 Aug 2016, 05:02:07 EST Thu, 04 Aug 2016, 06:11:20 EST Mon, 15 Aug 2016, 12:05:41 EST Thu, 18 Aug 2016, 12:22:01 EST Thu, 18 Aug 2016, 12:40:46 EST Mon, 22 Aug 2016, 10:52:44 EST Sat, 05 Aug 2017, 02:30:19 EST Filtered Full Citation counts:   Cited 45 times in TR Web of Science Cited 123 times in Scopus Search Google Scholar Access Statistics: 633 Abstract Views, 2 File Downloads  -  Detailed Statistics Created: Thu, 18 Aug 2016, 12:22:00 EST