Association of estimated daily lactose consumption, lactase persistence genotype (rs4988235), and gut microbiota in healthy U.S. adults

Authors: Kable, Mary; CHIN, ELIZABETH - University Of California, Davis; Huang, Liping; Stephensen, Charles; Lemay, Danielle

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/21/2023
Publication Date: 6/23/2023
Citation: Kable, M.E., Chin, E., Huang, L., Stephensen, C.B., Lemay, D.G. 2023. Association of estimated daily lactose consumption, lactase persistence genotype (rs4988235), and gut microbiota in healthy U.S. adults. Journal of Nutrition. https://doi.org/10.1016/j.tjnut.2023.06.025.
DOI: https://doi.org/10.1016/j.tjnut.2023.06.025

Interpretive Summary: We examined the gut bacteria and amount of lactose consumed in a healthy multiethnic U.S. adult cohort. Individuals who were genetically lactose intolerant (lacking the enzyme lactase) tended to consume less lactose per day than individuals who were not genetically lactose intolerant. However, lactose intolerant individuals who consumed more than 12.4 g/d of lactose per day, had significantly more gut bacteria from family Lactobacillaceae (full cohort) or Lachnospiraceae (Caucasian and Hispanic only). Many bacteria in these families are capable of metabolizing lactose. These data suggest that the gut bacteria of lactose intolerant individuals who consume high amounts of lactose, may be altered to accommodate increased lactose in the gut.

Technical Abstract: Objectives: Lactase persistence (LP) is a heritable trait in which lactose can be digested throughout adulthood. Lactase non-persisters (LNP) who consume lactose may experience microbial adaptations in response to the undigested lactose. The objective of the study was to estimate lactose from foods reported in the Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24) and to determine the interaction between lactose consumption, LP genotype and gut microbiome in an observational cross-sectional study of healthy U.S. adults. Methods: Average daily lactose consumption was estimated for N = 279 healthy U.S. adults, genotyped for the lactase gene -13910G>A polymorphism (SNP ID: rs4988235), by matching ASA24-reported foods to foods in the Nutrition Coordinating Center Food and Nutrient Database. Analysis of covariance was used to identify whether the A genotype (LP) influenced lactose and total dairy consumption with total energy intake and weight as covariates. The 16S rRNA V4/V5 region, amplified from bacterial DNA extracted from each frozen stool sample, was sequenced using Illumina MiSeq (300 bp PE) and analyzed using Qiime 2 (v 2019.10). Differential abundances of bacterial taxa were analyzed using DESeq2 likelihood ratio tests. Results: Across a diverse set of ethnicities, LP subjects consumed more lactose than LNP subjects. When stratifying by sex, there were no significant differences in intake among women. However, LP men consumed more lactose than LNP men. The abundance of family Lactobacillaceae was significantly associated with the interaction between LP genotype and lactose intake when accounting for sex. Lactobacillaceae abundance was highest in LNP subjects who consumed more than 12.46g/d (upper tercile). Within Caucasians and Hispanics, family Lachnospiraceae was significantly enriched in the gut microbiota of LNP individuals consuming the upper tercile of lactose across both sexes. Conclusions: Maximal lactose intake by lactase non-persisters exceeding 12.4 g/day suggests alternate routes of lactose catabolism. Increased abundance of family Lactobacillaceae and Lachnospriaceae, taxa that contain multiple genera capable of utilizing lactose, in LNP individuals consuming >12.4 g lactose/day suggests that several genera within this taxon may metabolize lactose in LNP adults.