The Impact of Microbiota on Brain and Behavior: Mechanisms & Therapeutic Potential
Abstract
There is increasing evidence that host-microbe interactions play a key role in maintaining homeostasis. Alterations in gut microbial composition is associated with marked changes in behaviors relevant to mood, pain and cognition, establishing the critical importance of the bi-directional pathway of communication between the microbiota and the brain in health and disease. Dysfunction of the microbiome-brain-gut axis has been implicated in stress-related disorders such as depression, anxiety and irritable bowel syndrome and neurodevelopmental disorders such as autism. Bacterial colonization of the gut is central to postnatal development and maturation of key systems that have the capacity to influence central nervous system (CNS) programming and signaling, including the immune and endocrine systems. Moreover, there is now expanding evidence for the view that enteric microbiota plays a role in early programming and later response to acute and chronic stress. This view is supported by studies in germ-free mice and in animals exposed to pathogenic bacterial infections, probiotic agents or antibiotics. Although communication between gut microbiota and the CNS are not fully elucidated, neural, hormonal, immune and metabolic pathways have been suggested. Thus, the concept of a microbiome-brain-gut axis is emerging, suggesting microbiota-modulating strategies may be a tractable therapeutic approach for developing novel treatments for CNS disorders.
Keywords
Irritable Bowel Syndrome Brain Derive Neurotrophic Factor Chronic Fatigue Syndrome Intestinal Microbiota Neurodevelopmental DisorderAbbreviations
- 5-HT
5-Hydroxytryptamine
- APC
Antigen presenting cell
- ASD
Autism spectrum disorder
- BDNF
Brain derived neurotrophic factor
- CNS
Central nervous system
- DC
Dendritic cell
- DHA
Docosahexaenoic acid
- DSS
Dextran sodium sulphate
- EC
Enteroendocrine cells
- ECC
Enterochromaffin cells
- ENS
Enteric nervous system
- EPA
Eicosapentaenoic acid
- GABA
Gamma-aminobutyric acid
- GALT
Gut-associated lymphoid tissues
- GI
Gastrointestinal
- HDAC
Histone deacetylase
- HPA
Hypothalamic-pituitary-adrenal axis
- IBS
Irritable bowel syndrome
- IDO
Indoleamine-2,3-dioxygenase
- NMDAR
N-methyl-d-aspartate receptor
- NPY
Neuropeptide Y
- SCFA
Short chain fatty acid
- SSRI
Selective serotonin reuptake inhibitor
- TCA
Tricyclic antidepressant
- TDO
Tryptophan 2,3-dioxygenase
- Treg
The regulatory T cells
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