Abstract P459: Milk Intake, Host LCT Genotype and Gut Bifidobacteria in Relation to Obesity: Results From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Background: Previous studies in Europeans found that gut Bifidobacterium genus was elevated in lactose intolerant individuals. However, the interrelationship between milk intake, host lactase ( LCT ) genotypes and different Bifidobacteria species, and their implications for human diseases have not been well-studied. Methods: This study included 2141 participants aged 23-83 years with microbiome, genetics and 24 hour dietary recall data from the HCHS/SOL, a population-based cohort of US Hispanics/Latinos. Stool samples were analyzed by shotgun metagenomics sequencing. Results: A GWAS on Bifidobacterium genus confirmed the genome-wide significant LCT locus (rs4988235, P =3.7х10 –21 ) ( Fig A ), and 3 major Bifidobacteria species were also significantly associated with LCT ( B. longum P = 4.4х10 –17 , B. adolescentis P=2.9х10 –13 , B. bifidum P=3.1х10 –5 ). 779 adults with lactose tolerant genotype (GG) had higher milk intake but lower Bifidobacteria compared to 1372 lactose intolerant adults (AA/AG). There was a significant interaction between milk intake and LCT variant on Bifidobacterium (P int =0.0003), with a positive association between milk intake and Bifidobacterium only in lactose intolerant but not in tolerant people ( Fig B ). The association of Bifidobacterium with obesity was also modified by LCT genotype. In lactose intolerant people, higher Bifidobacterium was associated with lower BMI, waist circumference and fat mass index, whereas in tolerant people higher Bifidobacterium was associated with higher obesity measures ( Fig C ). Species-level analyses indicated that B. longum may account for the positive association with milk intake and inverse associations with obesity measures in lactose intolerant people, while other major species, B. adolescentis and B. bifidum , may contribute to the positive association with obesity measures in lactose tolerant people. Conclusion: Our data indicate that diet and LCT genotype may alter the Bifidobacterium composition in gut, with different associations with obesity.