Examining the gut microbiota in aging

Abstract

The human gut microbiome, comprised primarily of bacteria, plays a crucial role in overall health and physiology by regulating metabolism, immunity, and behavior through the microbiota-gut-brain axis (MGBA). Key functions include fermenting complex carbohydrates into short-chain fatty acids (SCFAs) that maintain gut integrity, modulating inflammation, and influencing energy homeostasis (i.e., food intake regulation). For example, SCFAs can play a role in food intake regulation by directly or indirectly influencing episodic appetite signals (ghrelin, glucagon-like peptide 1 [GLP-1]) and tonic appetite signals (leptin, insulin). Gut dysbiosis, or an imbalance in the gut microbiome, leads to altered metabolic processes, increased epithelial permeability, and systemic inflammation that contribute to health issues like metabolic dysfunction (type 2 diabetes [T2D]), cardiovascular disease, and neuropsychiatric conditions. Aging is associated with gut dysbiosis, which can affect energy homeostasis and increase the risk for age-associated comorbidities. Regular physical activity has been shown to improve gut health and food intake regulation in young adults. This project aimed to characterize gut microbial communities in active older adults (60 years +) (GUMS) compared to a sedentary cohort with type 2 diabetes (T2D) (DMP) and investigate how gut bacteria may be influenced by physical activity/cardiorespiratory fitness (CRF), body composition, appetite hormones, cardiometabolic health, and mental health. Data was analyzed from n=22 GUMS (active older adults) and n=6 DMP (sedentary older adults with T2D). Gut bacterial diversity and composition were assessed by sequencing of 16S amplicon DNA from participant stool samples. In-person data was collected to assess CRF (via peak oxygen consumption [VO2peak] test), body composition (via air displacement plethysmography), appetite hormones (from plasma blood samples), and cardiovascular health (blood pressure, arterial stiffness). Mental health was assessed using standardized questionnaires administered through Qualtrics. Diversity measures were not significantly different between physically active older adults (GUMS) and sedentary older adults with type 2 diabetes (DMP); however compositional differences were observed. A nonsignificant increased proportion of opportunistic pathogens is apparent in DMP, suggestive of gut dysbiosis in T2D. Further, lower CRF and higher body fat [observed in DMP] were linked to decreased gut microbial diversity and increased opportunistic pathogens. Fasted appetite hormones ghrelin and GLP-1 did not differ between groups, but insulin and glucose levels were higher in DMP, reflecting their diabetic condition. No correlations were found between gut microbial diversity and appetite hormones, though positive correlations were observed between appetite hormones and SCFA-producing taxa. Dietary patterns showed higher fat intake and lower fiber consumption in DMP, potentially contributing to dysbiosis and metabolic issues. It was also observed that hypertension medication was associated with reduced gut microbial diversity and increased opportunistic pathogens, indicating a potential dysbiotic effect of hypertension treatment. Future research should recruit a larger number of participants and conduct long-term studies comparing older and younger populations to further understand the impact of aging and habitual physical activity on the gut microbiome. Additionally, exploring broader ranges of appetite hormone values could clarify their associations with gut microbial composition. Further research is also required to confirm the dysbiotic effects of hypertension medication.