Gut Microbiota and Immune Modulatory Properties of Human Breast Milk Streptococcus salivarius and S. parasanguinis Strains.

Shuo Li,Chuanyan Che,Xiaoxin Wang,Ziyi Zhang,Chenwei Wang,Jie Cao,Yi Zhao,Yufeng Zhao,Liping Zhao,Linghua Wang,Na Li,Xin Yang,Xuejing Li,Jian Shen,Yue Li

doi:10.3389/fnut.2022.798403

Abstract

Human breast milk Streptococcus spp. are transferred to infant guts via breast feeding, but their effects on the gut microbiota and immunity remain unclear. In this study, we characterized gut microbiota and immune modulatory properties of human breast milk S. salivarius F286 and S. parasanguinis F278 that had been shown to be able to colonize gut. The two Streptococcus strains were orally administered to mouse pups individually at 1 × 107 cells/day from postnatal Days 1 to 21. At postnatal week 3 (the weaning period), S. salivarius F286 reduced the colonic microbiota α-diversity, increased 21 amplicon sequence variants (ASVs), including bacteria from Akkermansia, Intestinimonas, and Lachnospiraceae, and decreased 52 ASVs, including bacteria from Eubacterium, Bifidobacterium, Escherichia-Shigella, and Turicibacter; however, S. parasanguinis F278 didn't change the colonic microbiota. Both Streptococcus strains reduced the ileal mRNA expression of cytokine/transcription factor representatives of T helper (Th) cells, including IFN-γ (Th1), Gata3 (Th2), and TGF-β (Treg) in 2-week-old suckling mice, and promoted the ileal expression of Foxp3 and TGF-β, which are representatives of anti-inflammatory Treg cells, in 3-week-old weaning mice. The two Streptococcus strains exhibited anti-inflammatory potential when incubated in vitro with human peripheral blood mononuclear cells and TNF-α-treated gut epithelial HT29 cells. In C. elegans, both strains activated immune response genes, which was associated with their lifespan-prolonging effects. Our results suggest that S. salivarius F286 and S. parasanguinis F278 may exert regulatory (anti-inflammatory) roles in gut immunity and S. salivarius F286 can modulate gut microbiota, and highlight the probiotic potential of milk S. salivarius and S. parasanguinis strains.

Highlights

Human milk is an important inoculum for the pioneering commensal bacteria of the neonatal gut [1]
The results in in vivo neonatal mice and in vitro human peripheral blood mononuclear cells (PBMCs) and HT29 cells suggest that human breast milk S. salivarius F286 and S. parasanguinis F278 can exert a regulatory role in immunity, and the experiments with C. elegans indicate that the interaction of S. salivarius F286 and S. parasanguinis F278 with immunity is highly correlated with their lifespan-extending effect and may be beneficial for the host
This study has the limitation that the in vivo effects of human milk Streptococcus strains on intestinal immunity and microbiota were evaluated in mice gut that is a different ecosystem of human gut, our work with multiple animal and human cell models highlights the potential salutary functions of human milk Streptococcus strains in modulating immunity and gut microbiota

Summary

Introduction

Human milk is an important inoculum for the pioneering commensal bacteria of the neonatal gut [1]. It provides breastfed infants with 104-108 bacterial cells per day, which is estimated based on the average daily ingestion of 800 ml of breast milk by the infants [2]. Studies on the effects of milk Streptococcus strains on gut microbiota and immunity are quite limited even though Streptococcus spp. are one of the most prevalent and abundant bacteria in the milk of mothers from different geographic locations [11, 12]. It is necessary to study the capability of human breast milk Streptococcus strains to modulate gut microbiota and immunity [5, 17]

Methods

Results

Conclusion