Microbial phone line: linking gut and brain communication
The takeaway:
The gut and the brain communicate with each other, forming a connection known as the gut-brain axis
The gut-brain axis supports various functions in the body health and is associated with several gastrointestinal and neuropsychiatric disorders
Gut microbiota play an important role in the development of the central nervous system, through several pathways including the autonomic nervous system, immune activation, and synthesis of neuro-active molecules.
Read on for more!
This article is the first in a series that explores the relationship between the brain and the gut. The gut, which houses the enteric nervous system, has been dubbed the “second brain [1]." The gut-brain axis is associated with several functions and states in the body, including digestion, satiety, stress responses, mood, behavior, and temperament [1, 2]. The gut-brain axis is implicated in various disorder states including gastrointestinal issues such as chronic abdominal pain, gut inflammation, Irritable Bowel Syndrome, as well as neuropsychiatric disorders such as anxiety, depression, eating disorders, attention-deficit hyperactivity disorder, autism spectrum disorder and Asperger’s syndrome [1, 3].
There is a mounting body of evidence implicating the gut microbiota as a major contributor to gut-brain axis function. In this series, I will discuss the interactions between gut microbiota and the brain, focusing on how these relationships affect children, beginning with early brain development, then temperament and disorders in children, and lastly how to cultivate a thriving gut microbiota in children. I hope you’ll tune in for the full series.
Gut microbiota cross-communicate with the central nervous system (CNS); gut microbiota influence brain function and behavior, which in turn affects gut microbiota composition and activity [4]. This communication occurs through several pathways, including the neural, endocrine and immune systems [4]. The exact mechanism through which gut microbiota influence CNS function and brain development remains unknown, but there are several potential pathways, discussed below.
Vagus nerve. The vagus nerve is the major nerve of parasympathetic portion of the autonomic nervous system. Many effects of gut microbiota and probiotic bacteria appear to involve activation of the vagus nerve [4], and some research suggests that the signaling is actually dependent on the vagus nerve [5].
Immune activation. Gut microbiota directly influence the immune system, and the immune system has bidirectional communication with the CNS. Thus, the immune system is a likely candidate for transducing signals from gut microbiota to the CNS [4]. Additionally, gut microbiota can affect the levels of immune system modulators, called cytokines, which can directly influence brain function [4].
Tryptophan metabolism. Tryptophan is an essential amino acid that is a precursor to many things, including the neurotransmitter serotonin. A common probiotic bacterial strain, Bifidobacterium infantis, can affect the biosynthesis of tryptophan [6].
Microbial metabolites. As discussed many times on this blog, gut bacteria produce short chain fatty acids (SCFAs) as a byproduct of fermentation of dietary fiber. Bacteroides predominantly produce the SCFAs acetate and propionate; Firmicutes mainly produce butyrate [5]. These SCFAs can act on the neural system [4], and may influence a specialized immune cell, called microglia [7]. During brain development, microglia “prune” synapses to make neural connections stronger and more efficient. Mice lacking intestinal microbes had abnormal CNS maturation and brain function; supplementation with SCFAs restored the function [7].
Microbial neurotransmitters. In addition to SCFAs, gut microbes can also generate neurotransmitters, which are signaling molecules through which brain cells communicate [4, 5]. Lactobacillus and Bifidobacterium produce gamma-aminobutyric acid (GABA); Escherichia coli, Bacillus and Saccharomyces produce noradrenalin; Candida, Streptococcus, Escherichia and Enterococcus, produce serotonin, Bacillus produce dopamine and Lactobacillus produce acetylcholine [8, 9].
Microbial composition. Infection of mice with a parasite resulted in increased anxiety-like behavior, along with changes in tryptophan metabolism and increased cytokines [10]. Treatment with a probiotic improved the behavior, but not all of the other effects. This suggests that microbes signal to the brain using multiple routes.
References
Mayer, E.A., Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci, 2011. 12(8): p. 453-66.
Rhee, S.H., C. Pothoulakis, and E.A. Mayer, Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat Rev Gastroenterol Hepatol, 2009. 6(5): p. 306-14.
Reber, S.O., Stress and animal models of inflammatory bowel disease--an update on the role of the hypothalamo-pituitary-adrenal axis. Psychoneuroendocrinology, 2012. 37(1): p. 1-19.
Cryan, J.F. and T.G. Dinan, Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci, 2012. 13(10): p. 701-12.
Sandhu, K.V., et al., Feeding the microbiota-gut-brain axis: diet, microbiome, and neuropsychiatry. Transl Res, 2017. 179: p. 223-244.
Desbonnet, L., et al., Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience, 2010. 170(4): p. 1179-88.
Erny, D., et al., Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci, 2015. 18(7): p. 965-77.
Lyte, M., Probiotics function mechanistically as delivery vehicles for neuroactive compounds: Microbial endocrinology in the design and use of probiotics. Bioessays, 2011. 33(8): p. 574-81.
Barrett, E., et al., gamma-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol, 2012. 113(2): p. 411-7.
Bercik, P., et al., Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. Gastroenterology, 2010. 139(6): p. 2102-2112 e1.[if supportFields]><span style='font-size:11.0pt;line-height:115%; font-family:"Calibri","sans-serif";mso-ascii-theme-font:minor-latin;mso-fareast-font-family: Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:AR-SA'><span style='mso-element:field-end'></span></span><![endif]