Association of lactose intake and lactase persistence genotype with microbial taxa and function in healthy multi-ethnic U.S. adults

Authors: TANG, YIRUI - University Of California, Davis; Oliver, Andrew; Alkan, Zeynep; KORF, IAN - University Of California, Davis; Kable, Mary; Lemay, Danielle

Submitted to: Food & Function
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/1/2025
Publication Date: 8/29/2025
Citation: Tang, Y., Oliver, A.S., Alkan, Z., Korf, I., Kable, M.E., Lemay, D.G. 2025. Association of lactose intake and lactase persistence genotype with microbial taxa and function in healthy multi-ethnic U.S. adults. Food & Function. DOI https://doi.org/10.1039/D5FO01640A.
DOI: https://doi.org/10.1039/D5FO01640A

Interpretive Summary: The genetic ability to digest lactose (milk sugar) and dairy consumption habits may affect gut bacteria. We studied the diet, genetics, gut microbiome, and fecal metabolites of 330 healthy U.S. adults. We found that adults who are genetically unable to digest lactose but still consume significant amounts of dairy products have more bacteria in their gut that can break down lactose, compared to people who can naturally digest lactose. The study revealed that yogurt consumption was linked to higher levels of yogurt-associated bacteria in everyone's gut, regardless of their genetic makeup. Consumption of alternative milk products (like soy or almond milk) was associated with lower levels of beneficial compounds in the gut for all participants, suggesting these dairy alternatives might not provide the same gut health benefits as traditional dairy products.

Technical Abstract: Objectives: We investigated the relationship between lactase persistent (LP) genotype, dairy/lactose consumption, and the taxonomic and functional profiles of the fecal microbiome. We hypothesized that higher lactose intake by adults with lactase non-persistence (LNP) genotype would be associated with increased lactose-fermenting microbes, higher abundance of microbial '-galactosidase genes, and increased short-chain fatty acid (SCFA) levels in fecal samples. We also hypothesized a significant correlation between yogurt intake, yogurt-associated fecal microbes, and fecal SCFA levels. Methods: Participants from the USDA Nutritional Phenotyping Study, a cross-sectional observational study designed to assess how dietary factors impact human health, whose fecal microbiome profile was measured using shotgun metagenomic sequencing (n=330) were included in this analysis. Fecal SCFA levels were measured using GC-MS. Fecal microbiome taxonomy and gene abundance was quantified using shotgun metagenomic sequencing. Lactose consumption and yogurt intake were estimated based on ASA24 dietary recalls or Food Frequency Questionnaire. LP/LNP genotype was assessed by a single nucleotide polymorphism (SNP ID: rs4988235). Results: Several genera of lactic acid bacteria (Veillonella, Lactobacillus, Lacticaseibacillus, and Lactococcus) were differentially abundant between recent high-lactose consuming (> 10.0 g. lactose/day) and low-lactose consuming (< 3.3 g. lactose per day) individuals. Among Caucasian and Hispanic LNP participants, lactic acid bacteria and lactate-utilizing bacteria (Lacticaseibacillus, Lactobacillus, Megamonas, and Veillonella) were significantly more abundant in the recent high-lactose consuming individuals than low-lactose consumers. Lactase non-persisters had higher abundance of fecal microbial '-galactosidase genes than the persisters, independent of the lactose intake. Fecal samples from these high-lactose consuming LNP participants were also significantly associated with a shift towards more propionate. The abundance of the yogurt-associated microbe, Streptococcus thermophilus, was positively associated with yogurt intake independent of genotype. Alternative milk consumption was significantly negatively associated with fecal SCFAs both in the full cohort and the Caucasian/Hispanic subset, regardless of genotype. Conclusions: Among adults who reportedly consumed >10 g recent 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. Regardless of host genotype, consumption of alternative milk may be associated with reduced production of health-promoting intestinal metabolites.