Probiotics combat sarcopenia by restoring gut integrity in Alzheimer’s disease

Background and Aims: Patients with Alzheimer’s disease (AD) exhibit muscle decline and physical compromise. Probiotic supplements may mitigate muscle decline and physical impairment; however, empirical investigations remain limited. We hypothesized that probiotics improve muscle strength and physical performance by repairing intestinal leak in AD patients. Methods: We conducted a randomized, double-blind, monocenter trial of AD patients receiving either a placebo (n = 54, 68–84 years old) or a probiotic (Vivomixx 112 billion*, one capsule daily, n = 51, 72–84 years old) for four months. We measured handgrip strength (HGS), body composition, the Short Physical Performance Battery (SPPB), and plasma zonulin, a marker of intestinal permeability, in patients with AD at baseline and after 4 months. Results: Four months of probiotic supplementation improved HGS, gait speed, and total SPPB scores, accompanied by reduced plasma zonulin (all p < 0.05). Patients with sarcopenia or reduced physical capacity (SPPB≤8) exhibited higher zonulin levels. Plasma zonulin was negatively associated with HGS, gait speed, and SPPB scores in univariate analyses (all p < 0.05). Multivariate models adjusting for age, cognition, body mass index, and nutritional status confirmed independent associations of zonulin with functional performance, particularly HGS and gait speed. Probiotics also reduced circulating markers of inflammation and oxidative stress. These results are derived from a male‑only cohort and may not be directly generalizable to female patients. Conclusion: Collectively, probiotics improve HGS and physical capacity by strengthening the intestinal barrier and reducing systemic inflammation and oxidative stress. Further studies should investigate the relative molecular and cellular mechanisms.