Correlating Gut Microbiome Characteristics with Changed Behavior in Aging Mice

The composition of the gut microbiome influences health and aging. In addition to variations between individuals, the relative abundances of different microbial populations making up the gut microbiome change with age in ways that contribute to chronic inflammation and the loss of useful metabolite production. Researchers here demonstrate that it is possible to correlate aspects of this gut microbiome aging with changes in behavior normally observed in aged mice. The gut microbiome is becoming an attractive target for intervention, given that strategies such as fecal microbiota transplantation can produce a lasting restoration of a more youthful gut microbe configuration.

In this study, we evaluated the locomotor activity, sensory function, and cognitive level of young (3 month old) and aged (22 month old) female C57BL/6J mice through a series of behavioral tests. The physiological functions, gut microbiota, and their metabolites of young and aged mice were comparatively analyzed from the perspective of the microbiota-gut-brain axis (MGBA). Our study focused on the alterations in the microbiota and metabolites induced by aging, and whether such alterations affect systemic inflammation and inflammation of related brain region through the MGBA to mediate abnormal behaviors.

Decreased locomotor activity, decreased pain sensitivity, and reduced respiratory metabolic profiling were observed in aged mice. High-throughput sequencing revealed that the levels of genus Lactobacillus and Dubosiella were reduced, and the levels of genus Alistipes and Bacteroides were increased in aged mice. Certain bacterial genus were directly associated with the decline of physiological behaviors in aged mice. Furthermore, the amount of fecal short-chain fatty acids (SCFAs) in aged mice was decreased, accompanied by an upregulation in the circulating pro-inflammatory cytokines and increased expression of inflammatory factors in the brain.

Aging-induced microbial dysbiosis was closely related with the overall decline in behavior, which may attribute to the changes in metabolic products, e.g., SCFAs, caused by an alteration in the gut microbiota, leading to inflammaging and contributing to neurological deficits. Investigating the MGBA might provide a novel viewpoint to exploring the pathogenesis of aging and expanding appropriate therapeutic targets.



Polycystic ovary syndrome (PCOS), an endocrine disorder afflicting 6-20% of women of reproductive age globally, has been linked to alterations in the gut microbiome. We previously showed that in PCOS, elevation of Bacteroides vulgatus in the gut microbiome was associated with altered bile acid metabolism. Here we show that B. vulgatus also induces a PCOS-like phenotype in female mice via an alternate mechanism independent of bile acids. We find that B. vulgatus contributes to PCOS-like symptoms through its metabolite agmatine, which is derived from arginine by arginine decarboxylase. Mechanistically, agmatine activates the farnesoid X receptor (FXR) pathway to subsequently inhibit glucagon-like peptide-1 (GLP-1) secretion by L cells, which leads to insulin resistance and ovarian dysfunction. Critically, the GLP-1 receptor agonist liraglutide and the arginine decarboxylase inhibitor difluoromethylarginine ameliorate ovarian dysfunction in a PCOS-like mouse model. These findings reveal that agmatine-FXR-GLP-1 signalling contributes to ovarian dysfunction, presenting a potential therapeutic target for PCOS management.

Posted by: Rob at May 21st, 2024 7:51 AM
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