Nutr Res Pract.  2023 Oct;17(5):883-898. 10.4162/nrp.2023.17.5.883.

Probiotic supplementation has sexdependent effects on immune responses in association with the gut microbiota in community-dwelling older adults: a randomized, double-blind, placebocontrolled, multicenter trial

• Kim CS
• Jung MH
• Choi EY
• Shin DM

• KMID: 2546946
• DOI: http://doi.org/10.4162/nrp.2023.17.5.883

Abstract

BACKGROUND/OBJECTIVES
Probiotics have been suggested as potent modulators of agerelated 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.

Keyword

Probiotics; gut microbiota; fluorescence-activated cell sorting; healthy aging; sex difference

Figure

• 

  Fig. 1 Changes in gut microbial community by sex. Relative abundances of the phyla (A) Bacteroidetes, (B) Firmicutes, and (C) the F/B ratio measured over the course of the intervention are shown as bar graphs. Data are presented as the mean (SEM). (D-E) Heatmap showing the changes in the relative abundances of the gut bacteria that were significantly shifted by probiotic supplementation over the course of the intervention in (D) men and (E) women. The color keys indicate the relative abundances.F/B, Firmicutes to Bacteroidetes.*P < 0.05, based on Mann–Whitney U test for the comparison of changes from baseline between the two groups in each sex group.

• 

  Fig. 2 Network meta-analysis on association between the gut microbiota and immune markers by sex. (A) Network meta-analysis results for the delta values of variables by sex. The thickness of the solid line indicates the strength of association. Blue and red colors of the solid line indicate the positive and negative correlation, respectively. Node with red colors indicates significant results. (B) Spearman’s rank correlation analysis between the rank of variables by sex.CRP, C-reactive protein; DC, dendritic cell; LBP, lipopolysaccharide-binding protein.

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