Some portion of the benefits of exercise and physical fitness arise through effects on the composition and activity of the gut microbiome. Here, for example, researchers provide evidence for exercise to reduce the production of an inflammatory microbial metabolite, TMAO. That the composition of the gut microbiome changes with age in ways that increase the production of inflammatory metabolites is one of many issues that might be corrected via approaches such as fecal microbiota transplantation, flagellin immunization, or the development of much more sophisticated probiotic combinations of microbes than presently exist. Animal studies suggest that significant improvements to later life health can be achieved via rejuvenation of the gut microbiome.
The metabolites produced by the gut microbiota play a role in age-related cognitive decline through the gut-brain axis. Within this axis, trimethylamine N-oxide (TMAO) permeates the intestinal epithelial barrier and enters systemic circulation, triggering inflammation in the central nervous system and ultimately leading to cognitive decline. However, it remains unclear whether exercise training’s specific mechanism for delaying age-related cognitive decline is associated with TMAO regulation and inhibition of neuroinflammation.
An aging rat model was established by intraperitoneal injection of D-galactose in Sprague Dawley rats, while simultaneous exercise training and TMAO interventions were conducted. The effects of exercise on cognitive function were evaluated using the new object recognition (NOR) test, the Morris water maze (MWM) test, and the radial arm maze (RAM) test. Additionally, the expression levels of TMAO and NLRP3 inflammasome-related proteins in aging rats were measured.
Exercise training effectively delayed the cognitive dysfunction induced by D-galactose in aging rats, as evidenced by a 22.6% increase in the discrimination index in the NOR test, an 11.2% prolongation of time in the target quadrant and a 50% enhancement in the number of platform crossings in the MWM test, and a 41.8% improvement in working memory in the RAM test. This neuroprotective effect is potentially mediated through the inhibition of the intestinal metabolite TMAO (with plasma TMAO levels reduced by 40.3%) and subsequent modulation of the TXNIP-NLRP3-Caspase-1–GSDMD inflammatory pathway.
