Maternal Administration Of Probiotic Lactobacilli Since Pre-Conception Programs Offspring Gut Microbiota Functions

OBJECTIVES: Probiotics intake may be considered beneficial by prospective and pregnant mothers but their effects on offspring development are underexplored. The maternal gut microbiota is a determinant of early offspring gut microbial colonization patterns and pre-conception may be a critical period. Our aim was to assess the programming effects of a probiotic Lacticaseibacillus rhamnosus R0011 and Lactobacillus helveticus R0052 mixture, which is known to support intestinal homeostasis in infancy, on the temporal dynamics of offspring gut microbiota functions. METHODS: Female C57BL/6 specific pathogen free mice received sterile or probiotic-supplemented water starting one week before mating and until weaning (postnatal day, PND, 21). Offspring remained on their respective mother's treatment from PND 21 to 36. Offspring cecal microbiota was profiled at PND 14, 21, and 36 by 16S rRNA (V3-V4) gene amplicon sequencing and metabolic pathways were inferred with PICRUSt2 and the MetaCyc database. Data analysis and clustering were conducted with DESeq2-Wald test and hclust in R. RESULTS: 355 MetaCyc pathways were predicted and collapsed into 48 functional classes; 10 of these accounted for more than 80% of the total pathway relative abundance, including various biosynthetic as well as carbohydrate and protein degradation pathways. With time, 113 and 55 pathways were altered (q-values < 0.01) in the control and probiotic groups, respectively, but only control samples clustered by age. At PND 14 and 21,195 and 39 pathways were differentially represented in the probiotic group vs. controls, but none at PND 36. Age-dependent pathways altered by probiotic supplementation belonged to biosynthesis (Amino Acid, Nucleoside and Nucleotide, Cofactor, Electron Carrier, and Vitamin) and degradation (Carbohydrate, Nucleoside and Nucleotide, Secondary Metabolite Degradation, C1 Compound Utilization and Assimilation) functional classes. CONCLUSIONS: Maternal probiotic supplementation accelerates the establishment of gut microbiota metabolic functions necessary to process host diet as well as for the synthesis of metabolites relevant for host health in the juvenile offspring. FUNDING SOURCES: NSERC; Lallemand Health Solutions; Lawson Family Chair in Microbiome Research.