Limosilactobacillus reuteri Strains Differentially Stimulate Immunity in Response to Human Milk Oligosaccharides in Newborn Mice

Probiotic Limosilactobacillus reuteri DSM 17938 reduces autoimmunity in mouse models. Recently, a novel strain, L. reuteri DSM 32846 (BG-R46 (R)), derived from DSM 17938 was found to have unique properties including bile acid tolerance and enhanced adenosine production. Human milk oligosaccharides (HMOs) help establish the intestinal microbiome and assist immune and neurodevelopment. The objective of the study was to explore the differential effects of each strain (with or without HMOs) with respect to innate and adaptive immunity in the intestine of mice during early development at postnatal d8 (early stage), d14 (rapid growth stage), and d21 (at weaning). C57BL/6J mice received intragastric DSM 17938 or DSM 32846 individually or in combination with HMOs, a mixture of 2`-FL and 6`-SL, daily from d7 to d20. We subsequently assessed circulating and intestinal immune cell markers at d8, d14 and d21. Both strains promoted development of intestinal macrophages, natural killer cells, and activated T and B cells. The cellular responses in the intestine of d8 mice were boosted within one day of treatment with DSM 17938, as opposed to 1-2 weeks after treatment with DSM 32846. This delay could be reversed by supplementing HMOs along with DSM 32846. Both DSM 32846 and DSM 17938 facilitated dendritic cell maturation and enhanced regulatory T cell numbers in the intestines of these newborns. However, HMOs enhanced the effects of DSM 32846, but not DSM 17938. Therefore, an early-life boost of intestinal immune cells by probiotics was observed which could be essential to protection against neonatal inflammatory conditions. This novel difference between two strains of the same species in immune modulation could provide a rationale for co-administration in an HMO-rich environment.