Development of Community-Wide Microbial Markers for Healthy and Dysbiotic Aging

Aging has become the main risk factor for multiple prevalent diseases such as cancer, cardiovascular disease, and neuodegeneration. These diseases are often associated with dysbiosis of the human microbiome which otherwise plays a crucial role in maintaining homeostasis for healthy aging. Consequently, microbiome dysbiosis has been recognized as one of the 12 hallmarks of unhealthy aging, termed dysbiotic aging in this proposal. Therefore, microbiome is a promising source of biomarkers that distinguish healthy from dysbiotic aging. However, at least two challenges remain to solidify these biomarkers and their use in the clinics in the broader population: 1) logistical barriers for recruiting large human cohorts that represent the highly heterogeneous aging population, inclusive of both their first and secondary microbiomes; and 2) experimental barriers for understanding the functional shift in microbiome dysbiosis associated with aging. To address these challenges, this project aims to conduct a proof-of-concept study using manhole wastewater microbiome for community-wide microbial marker discovery and functional assessment. Manhole wastewater continuously collects the human microbiomes from a community of individuals, making it a highly promising sample for comprehensive measurement of the microbiomes affecting our health. Usage of untreated wastewater circumvents the logistical barriers to recruiting human subjects. Targeted communities will be age-stratified, including university dorms (young adult population), independent senior living homes (elderly population), and assisted living facilities (advanced elderly population). This approach offers a novel perspective for aging at the community scale and provides assessment of important microbial markers for aging. To gain functional insight of the primary and secondary microbiomes, we will further investigate how the microbiomes respond to redox stress (simulated by a novel in vitro system) in the context of metabolic capacity (short chain acid production measurement) and antibiotic resistance (antibiotic susceptibility testing). This is because redox imbalance is a pathophysiological factor strongly associated with microbiome dysbiosis and unhealthy aging, yet the microbial contributions to redox stress and resilience remain unexplored. If successful, this project will identify microbial markers and their functions as preliminary indicators for healthy and dysbiotic aging on the community scale. In the short term, it will pave the way for expanding the same study to generate more robust microbial markers. Ultimately, it will help with developing new microbiome-based diagnostics for aging as well as community health.