Effect of Gut Microbiome Intervention on Aging Via Oral FMT

Effect of Fecal Microbiota Transplantation on Aging and the Underlying Mechanism of Gut Microbiome Restoration: a Randomized Clinical Trial

A severe public health issue facing global population is aging. Increasing preclinical and clinical data indicate the contribution of gut microbiome on aging and aging-related diseases such as cardiovascular disease, Alzheimer Disease, and diabetes. Interventions on microbiota are developed including prebiotics, probiotics, and fecal microbial transplantation (FMT). FMT via oral capsules also advances in recent with limited safety concerns compared with invasive routes. A hypothesis is thus raised that gut microbiome intervention via oral FMT can be a potential safe approach to encourage healthy aging, with multiple aspects evaluated for clinical phenotype of frailty, anthropometric measurement, cognitive function, cardiovascular aging, physical function, living activity, hippocampal volume, telomere length, cognitive biomarkers, inflammatory biomarkers, altered microbial composition and metabolites.

Objective: To explore the effect, safety and underlying mechanisms of gut microbiome intervention via FMT on aging. Study Design: A multi-center, randomized, blinded, placebo-controlled pilot study. Data quality control and statistical analysis: The investigators have invited professional statistic analysts to assist analyzing data and a third party to supervise data quality. Ethics: The Ethics Committee of Fuwai Hospital approved this study. Informed consents before patient enrollment are required.

Inclusion Criteria:

1. Age 70-85 years.
2. Patients with informed consent after thorough explanation.

Exclusion Criteria:

1. Participants of other clinical trials;
2. Antibiotics or probiotics usage within last 4 weeks;
3. Severe hepatic or renal diseases ((ALT >3 times the upper limit of normal value, or end stage renal disease on dialysis or eGFR <30 mL/min/1.73 m2, or serum creatinine >2.5 mg/dl [>221 μmol/L]);
4. History of large atherosclerotic cerebral infarction or hemorrhagic stroke (not including lacunar infarction and transient ischemic attack [TIA]);
5. Hospitalization for myocardial infarction within last 6 months; Coronary revascularization (PCI or CABG) within last 12 months; Planned for PCI or CABG in the next 6 months;
6. NYHA class III-IV heart failure; Hospitalization for chronic heart failure exacerbation within last 6 months;
7. Severe valvular diseases; Potential for surgery or percutaneous valve replacement within the study period;
8. Dilated cardiomyopathy; Hypertrophic cardiomyopathy; Rheumatic heart disease; Congenital heart disease;
9. History of dementia, Parkinson's disease, intracranial infection, intracranial tumor, schizophrenia, anxiety, depression;
10. History of neurosurgical operation;
11. History of gastrointestinal tumor, gastrointestinal surgery, inflammatory bowel disease; Hospitalization for peptic ulcer disease exacerbation within last 6 months or anticipated hospitalization for peptic ulcer disease the next 6 months;
12. Hypertension with uncontrolled blood pressure ≥180/110mmHg;
13. Diabetes Mellitus with uncontrolled fasting glucose level ≥200mg/dl (11.1mmol/L), or HbA1C>8%;
14. Addicted to alcohol; Use of medication influencing cognitive function(i.e., antihistamine, antipsychotic);
15. General anesthesia within last 3 months;
16. Other severe diseases influencing the entry or survival of participants, such as malignant tumor or acquired immune deficiency syndrome, life expectancy <1 year;
17. Impaired verbal communication who are incapable of providing their own informed consent, or incapable of self-care;
18. Special diet influencing microbiota (i.e. vegetarian);
19. Other conditions inappropriate for recruitment according to the investigators.