The discovery of a role of the intestinal microbiota in anxiety disorders that affect hundreds of millions of individuals worldwide represents hope for research into new treatments.
Anxiety disorders (phobias, post-traumatic stress, obsessive-compulsive, etc.), characterized by excessive chronic anxiety, affect 14% of the European population1.
The possible involvement of the microbiota
For 10 years, researchers have been evaluating the gut-flora influence on brain biochemistry and the results of a growing number of studies suggest a link between intestinal microbiota and anxiety disorders3,4,5,6,7,8. For example, a Canadian study published in 2011 analyzed the impact of intestinal microbiota transplants between different strains of mice (NIH Swiss and BALB/c) on their tendency to explore their environment less (fear or anxiety behavior). The findings showed that the “tendency to explore or not” behavior is transferable via the intestinal microbiota9.
Multiple pathways of action
Several potential pathways of action have already been identified. Some effects pass through the activation of the vagus nerve10, which acts on receptors for the neurotransmitter GABA, involved in the pathophysiology of anxiety disorders11 . Pathways via the blood (transportation of bacterial molecules that can pass through the blood–brain barrier), enteroendocrine pathways (stimulation of neuropeptide production by endocrine cells in the intestinal epithelium) and immune pathways (influence the production of pro- and anti-inflammatory cytokines) may also be involved12.
A step towards new treatments?
Currently, treatments for anxiety disorders are primarily psychotherapy and medications that act directly on the brain, like anxiolytics and antidepressants. Increasing numbers of researchers foresee the possibility of adding probiotics to this therapeutic arsenal13 . However, the efficacy of this approach remains to be proven.
1- Wittchen, H.-U. et al. (2011). The size and burden of mental disorders and other disorders of the brain in Europe 2010. European Neuropsychopharmacology, 21(9), 655-679. https://www.ncbi.nlm.nih.gov/pubmed/21896369
2- Diaz Heijtz R et al. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci USA 2011 ; 108 : 3047-52. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3041077/pdf/pnas.201010529.pdf
3- Clarke G et al. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry 2013 ; 18 : 666-73. https://www.ncbi.nlm.nih.gov/pubmed/?term=The+microbiome-gut-+brain+axis+during+early+life+regulates+the+hippocampal
4- Nishino R et al. Commensal microbiota modulate murine behaviors in a strictly contamination-free environment confirmed by culture-based methods. Neurogastroenterol Motil 2013 ; 25 : 521-8. https://www.ncbi.nlm.nih.gov/pubmed/?term=Commensal+microbiota+modulate+murine+behaviors+in+a+strictly+contamination-+free+environment+confirmed+by+culture-based+methods
5- Crumeyrolle-Arias M et al. Absence of the gut microbiota enhances anxiety-like behavior and neuroendocrine response to acute stress in rats. Psychoneuroendocrinology 2014 ; 42 : 207-17. https://www.ncbi.nlm.nih.gov/pubmed/?term=Absence+of+the+gut+microbiota+enhances+anxiety-like+behavior+and+neu-+roendocrine+response+to+acute+stress+in+rats.
6- Neufeld KM et al. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil 2011 ; 23 : 255-64. https://www.ncbi.nlm.nih.gov/pubmed/?term=Reduced+anxiety-like+behavior+and+central+neurochemical+change+in+germ-free+mice
7- Desbonnet L et al. Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour. Brain Behav Immun 2015 ; 48 : 165-73. https://www.ncbi.nlm.nih.gov/pubmed/25866195
8- Savignac HM et al. Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice. Neurogastroenterol Motil 2014 ; 26 : 1615-27. https://www.ncbi.nlm.nih.gov/pubmed/?term=Bifidobacteria+exert+strain-specific+effects+on+stress-related+behavior+and+phy-+siology+in+BALB%2Fc+mice
9- Bercik P et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 2011 ; 141 : 599-609. https://www.ncbi.nlm.nih.gov/pubmed/?term=The+intestinal+microbiota+affect+central+levels+of+brain-derived+neurotropic+factor+and+behavior+in+mice
10- Bravo JA et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci USA 2011 ; 108 : 16050-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179073/pdf/pnas.201102999.pdf
11- Kumar K et al. Therapeutic potential of GABA(B) receptor ligands in drug addiction, anxiety, depression and other CNS disorders. Pharmacol Bio- chem Behav 2013 ; 110 : 174-84. https://www.ncbi.nlm.nih.gov/pubmed/?term=Therapeutic+potential+of+GABA(B)+receptor+ligands+in+drug+addiction%2C+anxiety%2C+depression+and+other+CNS+disorders
12- Collins SM et al. The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol. 2012;10:735–42. doi: 10.1038/nrmicro2876. https://www.ncbi.nlm.nih.gov/pubmed/23000955
13- Lye Huey Shi et al. (2016). Beneficial properties of probiotics. Tropical Life Sciences Research 27(2): 73–90. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031164/pdf/tlsr-27-2-73.pdf