Modulating Gut Microbe Populations to Generate More Butyrate, thus Raising BDNF Levels and Improving Cognitive Function

The microbial populations of the gut have an influence on health and the progression of aging via the molecules that they generate, and which our cells react to. It isn't entirely clear as to the ordering of cause and effect in the detrimental changes that take place with aging in intestinal tissue, immune system, diet, and microbial populations. Studies have shown, however, that restoring more youthful populations can influence the function of tissues throughout the body, including the brain. The authors of this open access paper discuss modulating gut microbial populations in rats so as to upregulate butyrate production and BDNF levels, thereby improving some aspects of cognitive function. Similar examples exist in the literature for a range of other organs and tissues; it is an interesting area of research, though ultimately the size of the effects are probably not all that different from those relating to exercise or diet.

Neuroinflammation is correlated with a decline in cognitive function and memory, primarily because inflammation of the hippocampus tends to cause deleterious changes in synaptic transmission and plasticity. Because BDNF helps to sustain and enhance long-term potentiation (LTP) induction, it serves an essential role in cognitive function. Aging is associated with decreased levels of BDNF, suggesting that the maintenance of adequate BDNF concentrations could potentially help to preclude or delay the onset of cognitive impairment.

One convenient way to raise BDNF levels is supplementation of butyrate, a short-chain fatty acid (SCFA) that functions as a histone deacetylase inhibitor. Butyrate maintains the relaxation of chromatin and thereby enhances BDNF expression in the hippocampus. Secretion of pro-inflammatory cytokines may also be inhibited by BDNF, as the latter molecule interferes with activation of nuclear factor-kappa beta (NF-κβ). In addition, the expression of enzymes involved in the production of glutathione (GSH) may also be triggered by butyrate secretion. GSH is an antioxidant enzyme that relieves oxidative stress - another neurodegenerative risk factor.

The intestinal microbiota is responsible for a significant proportion of SCFA production. However, levels of SCFA decline with age due to dysbiosis, a microbial imbalance that often results in a considerable increase in pathological bacteria (Proteobacterium) at the expense of mutualistic ones (Bifidobacterium). Progression of gut dysbiosis has been linked to chronic systemic inflammation, including inflammation of the brain. Supplementation with probiotics and prebiotics may counteract the damaging effects that aging has on the brain by not only lessening inflammation and oxidative stress but also by increasing neurotrophic factors and neuronal plasticity.

A study was conducted to test how probiotic and prebiotic supplementation impacted spatial and associative memory in middle-aged rats. The results showed that rats supplemented with the symbiotic (both probiotic and prebiotic) treatment performed significantly better than other groups in the spatial memory test, though not in that of associative memory. The data also showed that this improvement correlated with increased levels of BDNF, decreased levels of pro-inflammatory cytokines, and better electrophysiological outcomes in the hippocampi of the symbiotic group. Thus, the results indicated that the progression of cognitive impairment is indeed affected by changes in microbiota induced by probiotics and prebiotics.

Link: https://doi.org/10.4103/bc.bc_34_19a

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