Can live microbial interventions support healthy aging? A systematic review and meta-analysis of cognitive and muscle outcomes in aging adults

Abstract

Introduction Preserving cognitive and physical function is central to healthy aging, and the gut microbiota may influence both brain and muscle physiology. We evaluated whether live microorganism-based interventions affect cognitive and muscle-related outcomes in aging adults. Methods We systematically reviewed randomized placebo-controlled trials of probiotics, synbiotics, or fecal microbiota transplantation in populations with a mean age of at least 60 years. MEDLINE, Embase, Web of Science, and the Cochrane Library were searched. Random-effects meta-analyses used Hedges’ g when at least three studies or independent comparisons reported sufficiently comparable outcomes. The protocol was prospectively registered in PROSPERO (CRD420251065993; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251065993). Results Twenty-four trials involving 1,809 participants were included qualitatively: 20 evaluated cognitive outcomes and four evaluated muscle-related outcomes. Eleven unique studies contributed to at least one meta-analysis. For Mini-Mental State Examination scores, the overall pooled estimate was positive (g = 1.02; 95% CI: 0.36–1.68; I2 = 90.84%). In exploratory post hoc subgroup analyses, the estimate was positive in Alzheimer’s disease (g = 1.46; 95% CI: 1.14–1.79) but not statistically significant in broader cognitive impairment (g = 0.49; 95% CI: −0.78 to 1.77); the subgroup difference was not significant (p = 0.15). Excluding both Akhgarjand et al. intervention arms yielded a positive estimate in Alzheimer’s disease (g = 1.63; 95% CI: 1.21–2.06), although only two studies remained. The pooled Repeatable Battery for the Assessment of Neuropsychological Status result was not statistically significant (g = 0.46; 95% CI: −0.50 to 1.41). Handgrip strength showed a modest positive estimate (g = 0.46; 95% CI: 0.06–0.85), but exclusion of Qaisar et al. attenuated it to non-significance (g = 0.23; 95% CI: −0.27 to 0.73). Discussion Live microorganism-based interventions showed preliminary short-term functional signals, but the small evidence base, high cognitive heterogeneity, short follow-up, and sensitivity to individual studies preclude firm efficacy conclusions. Subgroup and two-study sensitivity findings are exploratory. No eligible fecal microbiota transplantation trial was identified, so the evidence derives exclusively from probiotic and synbiotic studies. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251065993, unique identifier: CRD420251065993.