The relationship between protein intake, gut microbiome, inflammaging and loss of mobility in older adults

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This K01 application is for Dr. Samaneh Farsijani to establish a research career in Nutritional Epidemiology and acquire skills to integrate omics (gut microbiome) and non-omics (dietary intake) data towards her long-term goal in “Precision Nutrition” to develop age-specific dietary recommendations, replacing the current one-size-fits-all approach, to promote healthy aging. The proposal is derived from the candidate’s extensive training in nutrition and interdisciplinary research background in biology and epidemiology. The proposed training goals are directed to advance candidate’s skills in 1) aging & nutritional epidemiology; 2) advanced biostatistics; 3) gut microbiome; and 4) career development. Acquired skills will be applied toward the proposed scientific goal to determine the relationships between protein intake, gut microbiome, inflammation, and mobility loss in older adults. Aging is associated with inefficient utilization of dietary proteins, due to anabolic resistance, which potentially leads to functional losses. Also, up to 50% of US older adults fail to meet the Recommended Dietary Allowance (RDA) for protein (0.8 g/kg body weight/d). Therefore, a higher protein intake, above the RDA (1.0-1.2 g/kg/d), has been suggested to compensate for changes in protein metabolism and to maintain muscle health in aging. However, this strategy has not been incorporated into dietary guidelines due to inconclusive evidence from small and short- term studies, which were unable to show the underlying mechanisms and causal relationships between protein intake and mobility function in older adults. Gut dysbiosis (i.e., changes in gut microbiome) and inflammaging (i.e., low-grade chronic inflammation in aging) have been linked to frailty in older adults. Since diet plays a key role in shaping the gut microbiome and inflammation, it may be speculated that the effects of protein intake on mobility function are mediated through alterations of dysbiosis and inflammaging. Our central hypotheses are: i) high protein intake reduces the risk of mobility limitation by ameliorating inflammaging; ii) different protein intake metrics are independently associated with gut microbiome and inflammaging; and iii) gut dysbiosis is associated with mobility impairment in older adults. This proposal will leverage data from Health, Aging & Body Composition (Health ABC), and Study of Muscle, Mobility & Aging (SOMMA) cohorts to address three Aims: Aim 1: To simulate a pragmatic clinical trial using the Health ABC cohort to determine i) the effect of protein intake on the risk of mobility limitation, and ii) its causal mediation by amelioration of inflammaging. Aim 2: a) To characterize the associations between different metrics of protein intake (i.e., quantity, source and within-day distribution pattern), gut microbiome composition, and fecal metabolites; and b) to determine the association between gut dysbiosis and inflammaging in SOMMA. Aim 3: To determine the cross-sectional associations between gut microbial composition and fecal metabolites with mobility (i.e., gait speed) in older adults from SOMMA. This project will broaden our insights into the influence of protein intake, as a modifiable factor, on gut microbiome, inflammaging, and muscle health in aging with the ultimate goal to drive age-specific dietary advice.