Molecular Neurobiology

, Volume 54, Issue 6, pp 4432–4451 | Cite as

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

  • Gerwyn Morris
  • Michael Berk
  • Andre Carvalho
  • Javier R. Caso
  • Yolanda Sanz
  • Ken Walder
  • Michael Maes
Article

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.

Keywords

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

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Tir Na NogLlanelliUK
  2. 2.IMPACT Strategic Research Centre, School of Medicine, Barwon HealthDeakin UniversityGeelongAustralia
  3. 3.Orygen Youth Health Research Centre and the Centre of Youth Mental Health, The Florey Institute for Neuroscience and Mental Health and the Department of PsychiatryUniversity of MelbourneParkvilleAustralia
  4. 4.Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of MedicineFederal University of CearáFortalezaBrazil
  5. 5.Department of Pharmacology, School of MedicineUniversity Complutense of MadridMadridSpain
  6. 6.Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)MadridSpain
  7. 7.Instituto de Investigación Hospital 12 de Octubre (Imas12)MadridSpain
  8. 8.Microbial Ecology, Nutrition & Health Research Unit, Institute of Agrochemistry and Food TechnologyNational Research Council (IATA-CSIC)PaternaSpain
  9. 9.Health Sciences Postgraduate Program, Health Sciences CenterState University of LondrinaLondrinaBrazil
  10. 10.Centre for Molecular and Medical Research, School of MedicineDeakin UniversityGeelongAustralia

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