Role of the Gut Microbiome on Lean Mass and Physical Function in Older Adults

Role of the Gut Microbiome and Serum Metabolome on Lean Mass and Physical Function in Older Adults

The investigators recently published significant associations between circulating gut bacteria-related metabolites with lean and skeletal muscle mass and with measures of physical function in older adults, evidence that suggests a role for gut bacteria on the maintenance of these outcomes. To date, studies aimed at identification of associations between gut bacteria with lean mass or with specific measures of physical function have yet to be reported. Accordingly, the over-arching hypothesis is that gut bacteria are associated with, and are causatively involved in mechanisms that underlie the maintenance of lean mass and physical function in older adults. Results obtained from the proposed study are intended as the basis for future studies aimed at targeted modulation of the gut microflora, which may be a novel and innovative means for improving lean mass and physical function, and for addressing the public health priority of healthy aging in older adults.

In older adults (70+ years), reduced lean body mass and physical function are associated with increased disability, hospitalization, morbidity and mortality. Because older adults are the fastest growing global subpopulation, identification of mechanisms that underlie the maintenance of lean mass and physical function will be important for addressing the public health priority of healthy aging.

Gut bacteria may be involved in mechanisms that underlie the maintenance of lean mass and physical function. In support of this hypothesis, in multiple publications the investigators recently reported significant associations between circulating gut bacteria-related metabolites with these outcomes in older adults. Accordingly, the overarching study hypothesis is that is gut bacteria are associated with, and are causatively involved in mechanisms that underlie the maintenance of lean mass and physical function in older adults. To test this hypothesis, the investigators propose to: characterize the association between fecal bacteria with lean mass and physical function (AIM 1), test the causative role of gut bacteria on the maintenance of lean mass and physical function by colonizing germ-free mice with fecal bacteria from older adults (AIM 2), and examine potential mechanisms that link gut bacteria with these outcomes by identifying associations between gut bacteria and serum metabolites with lean mass and physical function (AIM 3).

Inclusion Criteria:

i) Willing and able to sign the IRB approved informed consent form ii) Male and Female iii) 70-85 years of age iv) BMI ≤ 35 kg/m2 v) Willing to come to the HNRCA laboratory for baseline and 1-month follow-up study visits vi) SPPB ≥ 11 ("High-Functioning", HF; 20 subjects: 10 males, 10 females) vii) 4 ≤ SPPB ≤ 7 ("Low-Functioning", LF; 20 subjects: 10 males, 10 females)

Exclusion Criteria:

i) Non-English speaker ii) Acute or terminal illness iii) Surgery in the past 6 months iv) Lower extremity fracture within the past 6 months v) Myocardial infarction in the past 6 months vi) Coronary artery disease, peripheral vascular disease, previous stroke, or history of transient ischemic attacks vii) Cognitive impairment (MMSE score < 23) viii) Uncontrolled hypertension (> 160/100 mmHg) ix) Neuromuscular disease or drugs affecting neuromuscular function x) Androgen therapy in males xi) Estrogen therapy in females xii) Significant immune disorder xiii) Kidney Failure xiv) Pancreatic disease xv) Diabetes xvi) Gastrointestinal or malabsorption diseases xvii) History of cholecystectomy xviii) Use of probiotics, prebiotics or antibiotics in the past 3 months xix) The subject has any other condition, which in the opinion of the Investigator, precludes the subject's participation in the trial.

xx) With the goal of matching the HF and LF groups for age, sex,and BMI, subjects may be excluded because their age, sex or BMI puts them outside the range needed for this study.