Gut Microbiome and Cognitive Health

Recently published study (Bonham et al, 2023) shed light on the crucial role of the gut microbiome in brain development and cognitive functions. Some gut microbes, like Alistipes obesi and Blautia wexlerae, are linked to higher cognitive functions, while others such as Ruminococcus gnavus are more prevalent in children with lower cognitive scores.

Earlier research by Gareau (2014) and Tooley (2020) suggested that changes in gut microbiota affect cognitive behavior, with diverse microbiota correlating with improved cognitive flexibility and executive function. Fernández-Real (2015) found a specific gut-brain map in obese individuals, linking bacterial diversity to brain structure and cognitive function. Carlson (2018) extended these findings to infants, showing a connection between gut microbiota composition and cognitive outcomes.

Osadchiy et al. (2020) discovered that fecal microbiota-derived metabolites affect the connectivity of the amygdala, relating to emotions and obesity. In patients with irritable bowel syndrome (IBS), the abundance of Firmicutes and Bacteroidetes families correlates with brain structural changes in sensory integration and salience networks. 

Bifidobacterium strains positively affect mood and stress response, possibly by contributing to neurotransmitter production. Lactobacillus strains, found in fermented foods like yogurt, are linked to reduced anxiety and depression. Prevotella correlates with improved memory and cognition, while Akkermansia muciniphila supports gut lining health and indirectly influences brain function. Faecalibacterium prausnitzii's anti-inflammatory properties contribute to a balanced gut environment, crucial for neurological health.

The gut microbiome influences brain health through various mechanisms, such as stimulating the immune system, producing neurotoxic metabolites, creating hormones and neurotransmitters, and affecting the enteric nervous system. These processes impact sleep, stress reactivity, memory, mood, cognition, and are relevant to disorders like alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome. Gut bacteria generate compounds like SCFAs (butyrate, propionate, acetate) and neurotransmitters (GABA, serotonin), influencing cognitive function and mood. The gut microbiome's production of flavonoid metabolites might be harnessed to treat neurological disorders. Probiotics and nutraceuticals that enhance these metabolites offer promising avenues for improving health and treating mood, anxiety, and neurological disorders.

Maintaining beneficial gut symbionts is essential to prevent pathogenic organisms. A recent study showed that Klebsiella aerogenes in menopausal female mice (Li et al, 2023) could lead to depression by degrading estradiol.

Latest innovations in therapeutics targeting the gut-brain axis in include GRP119 and GRP40 combination - a G-protein coupled receptor (GPCR) mainly expressed in pancreas, intestine, and brain and a Gαs-coupled 7TM receptor activated by endogenous lipids such as oleoylethanolamide (OEA) and by the dietary triglyceride metabolite 2-monoacylglycerol.


REFERENCES

Bonham KS, Fahur Bottino G, McCann SH, Beauchemin J, Weisse E, Barry F, Cano Lorente R; RESONANCE Consortium; Huttenhower C, Bruchhage M, D'Sa V, Deoni S, Klepac-Ceraj V. Gut-resident microorganisms and their genes are associated with cognition and neuroanatomy in children. Sci Adv. 2023 Dec 22;9(51):eadi0497. doi: 10.1126/sciadv.adi0497. Epub 2023 Dec 22. PMID: 38134274; PMCID: PMC10745691.

Li, D.; Sun, T.; Tong, Y.; Le, J.; Yao, Q.; Tao, J.; Liu, H.; Jiao, W.; Mei, Y.; Chen, J.; et al. Gut-microbiome-expressed 3β-hydroxysteroid dehydrogenase degrades estradiol and is linked to depression in premenopausal females. Cell Metab.

Barrio C, Arias-Sanchez S, Martin-Monzon I. The gut microbiota-brain axis, psychobiotics and its influence on brain and behaviour: A systematic review. Psychoneuroendocrinology. 2022 Mar 1;137:105640.

Tang H, Chen X, Huang S, Yin G, Wang X, Shen G. Targeting the gut–microbiota–brain axis in irritable bowel disease to improve cognitive function–recent knowledge and emerging therapeutic opportunities. Reviews in the Neurosciences. 2023 Feb 10(0).

Osadchiy V, Mayer EA, Gao K, Labus JS, Naliboff B, Tillisch K, Chang L, Jacobs JP, Hsiao EY, Gupta A. Analysis of brain networks and fecal metabolites reveals brain-gut alterations in premenopausal females with irritable bowel syndrome. Transl Psychiatry. 2020 Nov 2;10(1):367. doi: 10.1038/s41398-020-01071-2. PMID: 33139708; PMCID: PMC7608552.

Galland L. The gut microbiome and the brain. Journal of medicinal food. 2014 Dec 1;17(12):1261-72.

Tooley KL. Effects of the Human Gut Microbiota on Cognitive Performance, Brain Structure and Function: A Narrative Review. Nutrients. 2020 Sep 30;12(10):3009. doi: 10.3390/nu12103009. PMID: 33007941; PMCID: PMC7601389.

Carlson AL, Xia K, Azcarate-Peril MA, Goldman BD, Ahn M, Styner MA, Thompson AL, Geng X, Gilmore JH, Knickmeyer RC. Infant Gut Microbiome Associated With Cognitive Development. Biol Psychiatry. 2018 Jan 15;83(2):148-159. doi: 10.1016/j.biopsych.2017.06.021. Epub 2017 Jun 27. PMID: 28793975; PMCID: PMC5724966.

Gareau MG. Microbiota-gut-brain axis and cognitive function. Adv Exp Med Biol. 2014;817:357-71. doi: 10.1007/978-1-4939-0897-4_16. PMID: 24997042.

Fernandez-Real JM, Serino M, Blasco G, Puig J, Daunis-i-Estadella J, Ricart W, Burcelin R, Fernández-Aranda F, Portero-Otin M. Gut Microbiota Interacts With Brain Microstructure and Function. J Clin Endocrinol Metab. 2015 Dec;100(12):4505-13. doi: 10.1210/jc.2015-3076. Epub 2015 Oct 7. PMID: 26445114.

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