Probiotic supplementation has sex-dependent effects on immune responses in association with the gut microbiota in community-dwelling older adults: a randomized, double-blind, placebo-controlled, multicenter trial.

Background/objectives: Probiotics have been suggested as potent modulators of age-related disorders in immunological functions, yet little is known about sex-dependent effects of probiotic supplements. Therefore, we aimed to investigate sex-dependent effects of probiotics on profiles of the gut microbiota and peripheral immune cells in healthy older adults.

Subjects/methods: In a randomized, double-blind, placebo-controlled, multicenter trial, healthy elderly individuals ≥ 65 yrs old were administered probiotic capsules (or placebo) for 12 wk. Gut microbiota was analyzed using 16S rRNA gene sequencing and bioinformatic analyses. Peripheral immune cells were profiled using flow cytometry for lymphocytes (natural killer, B, CD4⁺ T, and CD8⁺ T cells), dendritic cells, monocytes, and their subpopulations.

Results: Compared with placebo, phylum Firmicutes was significantly reduced in the probiotic group in women, but not in men. At the genus level, sex-specific responses included reductions in the relative abundances of pro-inflammatory gut microbes, including Catabacter and unclassified_Coriobacteriales, and Burkholderia and unclassified Enterobacteriaceae, in men and women, respectively. Peripheral immune cell profiling analysis revealed that in men, probiotics significantly reduced the proportions of dendritic cells and CD14⁺ CD16^- monocytes; however, these effects were not observed in women. In contrast, the proportion of total CD4⁺ T cells was significantly reduced in women in the probiotic group. Additionally, serum lipopolysaccharide-binding protein levels showed a decreasing tendency that were positively associated with changes in gut bacteria, including Catabacter (ρ = 0.678, P < 0.05) and Burkholderia (ρ = 0.673, P < 0.05) in men and women, respectively.

Conclusions: These results suggest that probiotic supplementation may reduce the incidence of inflammation-related diseases by regulating the profiles of the gut microbiota and peripheral immune cells in healthy elders in a sex-specific manner.