Role of the Gut Microbiome on Lean Mass and Physical Function 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 I recently
reported significant associations between circulating gut bacteria-related metabolites with
these outcomes in older adults. Accordingly, my overarching 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, I
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.