Sialic acid-based probiotic intervention in lactating mothers improves the neonatal gut microbiota and immune responses by regulating sialylated milk oligosaccharide synthesis via the gut–breast axis
Yushuang Wang,
Binqi Rui,
Xiaolei Ze,
Yujia Liu,
Da Yu,
Yinhui Liu,
Zhi Li,
Yu Xi,
Xixi Ning,
Zengjie Lei,
Jieli Yuan,
Liang Li,
Xuguang Zhang,
Wenzhe Li,
Yanjie Deng,
Jingyu Yan,
Ming Li
Affiliations
Yushuang Wang
Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian, China
Binqi Rui
Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian, China
Xiaolei Ze
Microbiome Research and Application Center, BYHEALTH Institute of Nutrition & Health, Guangzhou, China
Yujia Liu
Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian, China
Da Yu
The Third Ward of Obstetrics and Gynecology at Chunliu District, Dalian Women and Children Medical Center (Group), Dalian, China
Yinhui Liu
Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian, China
Zhi Li
Department of Clinical Laboratory, Central Hospital of Dalian University of Technology, Dalian, China
Yu Xi
Microbiome Research and Application Center, BYHEALTH Institute of Nutrition & Health, Guangzhou, China
Xixi Ning
Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian, China
Zengjie Lei
Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian, China
Jieli Yuan
Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian, China
Liang Li
Microbiome Research and Application Center, BYHEALTH Institute of Nutrition & Health, Guangzhou, China
Xuguang Zhang
Microbiome Research and Application Center, BYHEALTH Institute of Nutrition & Health, Guangzhou, China
Wenzhe Li
Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China
Yanjie Deng
The Third Ward of Obstetrics and Gynecology at Chunliu District, Dalian Women and Children Medical Center (Group), Dalian, China
Jingyu Yan
Dalian Institute of Chemical Physics, Chinese Academy of Sciences Key Laboratory of Separation Science for Analytical Chemistry, Dalian, China
Ming Li
Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian, China
ABSTRACTHuman milk oligosaccharides (HMOs) are vital milk carbohydrates that help promote the microbiota-dependent growth and immunity of infants. Sialic acid (SA) is a crucial component of sialylated milk oligosaccharides (S-MOs); however, the effects of SA supplementation in lactating mothers on S-MO biosynthesis and their breastfed infants are unknown. Probiotic intervention during pregnancy or lactation demonstrates promise for modulating the milk glycobiome. Here, we evaluated whether SA and a probiotic (Pro) mixture could increase S-MO synthesis in lactating mothers and promote the microbiota development of their breastfed neonates. The results showed that SA+Pro intervention modulated the gut microbiota and 6’-SL contents in milk of maternal rats more than the SA intervention, which promoted Lactobacillus reuteri colonization in neonates and immune development. Deficient 6’-SL in the maternal rat milk of St6gal1 knockouts (St6gal1−/−) disturbed intestinal microbial structures in their offspring, thereby impeding immune tolerance development. SA+Pro intervention in lactating St6gal1± rats compromised the allergic responses of neonates by promoting 6′-SL synthesis and the neonatal gut microbiota. Our findings from human mammary epithelial cells (MCF-10A) indicated that the GPR41-PI3K-Akt-PPAR pathway helped regulate 6′-SL synthesis in mammary glands after SA+Pro intervention through the gut – breast axis. We further validated our findings using a human-cohort study, confirming that providing SA+Pro to lactating Chinese mothers increased S-MO contents in their breast milk and promoted gut Bifidobacterium spp. and Lactobacillus spp. colonization in infants, which may help enhance immune responses. Collectively, our findings may help alter the routine supplementation practices of lactating mothers to modulate milk HMOs and promote the development of early-life gut microbiota and immunity.
