Researchers of a recent study published in Metabolism of Nature investigated the relationship between milk consumption and type 2 diabetes (T2D) among non-lactase-intolerant individuals (LNP).
Record
Cow’s milk is part of the human diet. However, its relationship with T2D is debatable. The effects of milk and dairy products on T2D risk are unclear and vary by population. Recent research reveals a link between the lactase gene (LCT), milk consumption and gut microbiota, with a genome-wide association study (GWAS) linking the host LCT locus to oligosaccharide/lactose-absorbing Bifidobacterium species milk and can be used as probiotics to reduce inflammation.
About the study
In the present study, researchers investigated whether consuming more milk reduces the risk of T2D in LNPs but not LPs by altering gut microbiota composition and circulating metabolites, potentially affecting host metabolic health.
The team conducted a GWAS of daily milk intake among 12,653 participants in the Hispanic Community Study/Study of Latinos (HCHS/SOL), identifying single nucleotide polymorphisms (SNPs) associated with milk intake. They calculated dietary intake using the National Cancer Institute (NCI) technique and quantified dairy intake in daily servings, divided into categories of milk, cheese, and yogurt.
The group genotyped blood-derived deoxyribonucleic acid (DNA) and analyzed serum metabolomics in 3,972 randomized patients who provided reference samples. Correlation analyzes included 624 known metabolites from more than 80% of subjects at baseline. They performed metagenomic sequencing on stool DNA obtained from 3,035 HCHS/SOL participants during follow-up.
The team used linear mixed-effects regression models to analyze milk intake among 12,653 subjects, controlling for field center, age, sex, first five principal components of genetic variation and sample weight. They divided participants into LCT-rs4988235 GG (LNP group) and LCT-rs4988235 AA/AG (LP group). They used multivariate Poisson regression models to investigate the relationships between daily consumption of milk, cheese and yogurt and the occurrence of T2D, stratified by LCT gene.
In addition, the team prospectively evaluated associations between metabolites associated with LCT genotype and T2D risk and their potential mediating effects on the relationship between milk intake and risk. Furthermore, they replicated the LCT-milk consumption interaction on T2D risk and the associations between circulating metabolites and T2D risk in the UK Biobank (UKBB) and Atherosclerosis Risk in Communities (ARIC) studies.
Results
The study showed that increased milk intake was associated with a reduced risk of T2D in people with LNP [relative risk (RR), 0.7] but not in lactase persisters (RR,1.2), controlling for demographic, socioeconomic, and behavioral characteristics. There were no associations with LCT genotype for cheese or yogurt consumption in the UKBB. Meta-analysis in nonwhite groups yielded comparable results (RR, 0.8). In contrast, a meta-analysis of 18 studies including mostly non-Hispanic white subjects with a high incidence of lactose intolerance revealed a slight positive association between milk consumption and T2D risk (RR, 1.0).
The Alternative Health Diet Index 2010 (AHEI 2010), which assesses diet quality, showed minimal relationships between diet components and milk intake, with comparable patterns between lactose-intolerant and lactose-intolerant adults. Further changes in AHEI-2010 or dietary components did not affect LCT-milk interactions on T2D risk or associations between milk consumption and diabetes-related metabolic characteristics.
The Analysis of Microbiome Composition (ANCOM) II survey revealed six and 13 factors associated with milk consumption in LP and LNP subjects, respectively. Seven species of Bifidobacterium and B. fragilis showed positive associations with milk consumption among LNP subjects. In contrast, five bacterial species, including Roseburia faecis, Bilophila wadsworthia and Prevotella, were associated with lower milk consumption. The team found positive associations between species within a genus and inverse associations between the genera Bifidobacterium and Prevotella.
Species associated with milk among non-lactose-intolerant individuals were typically unassociated with those among lactose-intolerant individuals, with similar results observed when examining associations independent of LCT genotype groups. Using linear regressions controlling for the variables included in the ANCOM-II analysis showed that the relationships between identified bacterial species and milk consumption were LCT gene specific, with significant LCT-milk gene interactions detected for most identified species .
Among 624 metabolites, the study identified 62 and 79 metabolites associated with milk consumption in LNP and LP subjects, respectively. The milk-related metabolite score for GG was strongly associated with reduced risk of T2D and positively with profiles of several metabolic traits. However, Mendelian randomization (MR) estimates for the remaining nine metabolites were non-significant.
conclusion
Overall, the study findings indicated a protective association between milk consumption and T2D in Hispanic/Latino individuals, likely related to gut microbiota and blood metabolites. LCT genotype may influence this interaction, with a strong protective association observed exclusively among LNP subjects.
This study helps to better understand the impact of milk consumption on human metabolic health by examining host genetics, gut microbes and circulating metabolites. Additional studies, including experimental trials, may confirm these findings.
