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

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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; I 2 = 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.