Objectives: We investigated the relationship between lactase persistent (LP) genotype, lactose consumption, and the taxonomic and functional profile of the fecal microbiome in healthy adults. We hypothesized that higher lactose intake by adults with lactase non-persistence (LNP) genotype will be associated with higher abundance of microbial beta-galactosidase genes and lactose-fermenting microbes. Methods: The USDA Nutritional Phenotyping Study is a cross-sectional observational study designed to assess how dietary factors impact human health. Lactose consumption was estimated based on at least two ASA24 dietary recalls. LP/LNP genotype was assessed by the single nucleotide polymorphism (SNP ID: rs4988235). Fecal microbiomes were evaluated using shotgun metagenomic sequencing (n=330). Results: Several genera of lactic acid bacteria were differentially abundant between recent high-lactose consuming ( > 10.0 g. lactose/day) and low-lactose consuming (< 3.3 g. lactose per day) individuals. These genera include Veillonella, Lactobacillus, Lacticaseibacillus, and Lactococcus. Among Caucasian and Hispanic LNP participants, lactic acid bacteria and lactate-utilizing bacteria (Lacticaseibacillus, Lactobacillus, Megamonas, and Veillonella) were significantly more abundant in the high-lactose consuming individuals compared to low-lactose consumers. There was no significant association between beta-galactosidase gene abundance with lactose intake, lactase genotype, or their interaction. Conclusions: Among adults who reportedly consumed >10 g lactose/day, those with LNP genotype had higher amounts of lactic acid bacteria and lactate-utilizing bacteria in their fecal samples compared to those with LP genotype. Funding Sources: California Dairy Research Foundation and USDA Agricultural Research Service.
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