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Association of Estimated Daily Lactose Consumption, Lactase Persistence Genotype (rs4988235), and Gut Microbiota in Healthy U.S. Adults

ABSTRACT: Abstract Objectives Lactase persistence (LP) is a heritable trait in which lactose can be digested into adulthood. Lactase non-persisters (LNP) who consume lactose may experience microbial adaptations in response to the undigested lactose. The objective of this study was to determine the interaction between lactose consumption, LP genotype and gut microbiota in an observational cross-sectional study of healthy U.S. adults. Methods ASA24 dietary data and stool samples were collected from healthy U.S. adults genotyped for the lactase persistence SNP ID: rs4988235 (n = 280). Lactose was estimated by matching ASA24-reported foods to foods in the Nutrition Coordinating Center Food and Nutrient Database. The 16S rRNA V4/V5 region, amplified from bacterial DNA extracted from each frozen stool sample, was sequenced using Illumina MiSeq (300bp PE) and analyzed using Qiime 2 (v 2019.10). Bacterial sequence counts present at greater than 0.1% of the total data set were analyzed using DESeq2 and LEfSe. Taxa that were differentially abundant by both analyses at the family or genus level are reported here. Results On average 246 ng/uL (3.9 – 646.5ng/uL) DNA was obtained from each sample, yielding 21,470 sequences (10,122 – 56,837). LP genotypes were unevenly distributed by ethnicity and Clostridium (family Lachnospiraceae) was significantly enriched in Asian ethnicities. Therefore, only Caucasian and Hispanic participants were grouped as LP (AA or AG genotype) or LNP (GG genotype) for further analysis. The abundance of Roseburia and family Lachnospriaceae was higher in the upper (>12.4g), relative to lower (< 5.78g), tertile of lactose consumption in LNP adults, but not in LP. Conclusions Increased abundance of Roseburia, a microbe capable of utilizing lactose, in LNP individuals consuming >12.4 g lactose/day suggests that this genus may metabolize lactose in LNP adults. Funding Sources The California Dairy Research Foundation and the United States Department of Agriculture, Agricultural Research Service.

SUBMITTER: Kable M

PROVIDER: S-EPMC7258441 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Project description:Abstract Objectives Lactase persistence (LP), a heritable trait in which lactose can be digested throughout adulthood, is often used to predict dairy intake. However, it is currently unknown how LP relates to daily lactose consumption in healthy US adults. 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 compare lactose and total dairy consumption in relation to LP genotypes. Methods ASA24 dietary data were collected from healthy Caucasians and Hispanics (n = 215) genotyped for the lactase persistence SNP ID: rs4988235. ASA24 outputs servings of dairy but not the nutrient lactose. Lactose was estimated by matching ASA24-reported foods to foods in the Nutrition Coordinating Center Food and Nutrient Database, which outputs lactose. Analysis of covariance was used to identify whether genotype influenced lactose and total dairy consumption with total energy intake and weight as covariates. Pairwise testing was conducted on the adjusted means using the Tukey adjustment to correct for multiple testing. Results Median lactose consumption for subjects with the AA genotype (homozygous LP) was 12.08 g (min: 0.91 g, max: 81.85 g), 10.05 g (min: 0.46 g, max: 45.82) for subjects with the AG genotype (heterozygous LP), and 8.97 g (min: 0.47, max: 38.96 g) for subjects with the GG genotype (homozygous lactase non-persistent). AA subjects consumed more lactose than GG subjects (P = 0.024). When stratifying by sex, there were no significant differences among genotypes in women, although GG women consumed the least amount of lactose compared to AA and AG women. AA men consumed more lactose than AG (P = 0.028) and GG men (P = 0.032). Subjects with the AA genotype consumed the most, and GG subjects the least amount of dairy. However, there were no significant differences in total dairy consumption among genotypes. Conclusions The median amount of lactose consumed daily by healthy adults is 9–12 g/day, with higher consumption by those with an LP genotype. Total dairy intake was not significantly influenced by genotype, highlighting the value in specifically estimating lactose consumption. Maximal lactose intake by lactase non-persisters exceeding 15 g/day suggests alternate routes of lactose catabolism. Funding Sources The California Dairy Research Foundation and the USDA-ARS.

Project description:Lactase persistence (LP) is a trait in which lactose can be digested throughout adulthood, while lactase non-persistence (LNP) can cause lactose intolerance and influence dairy consumption. One single nucleotide polymorphism (SNP ID: rs4988235) is often used as a predictor for dairy intake, since it is responsible for LP in people in European descent, and can occur in other ethnic groups. The objective of this study was to determine whether rs4988235 genotypes and ethnicity influence reported dairy consumption in the United States (U.S.). A food frequency questionnaire (FFQ) and multiple Automated Self-Administered 24-h recalls (ASA24®) were used to measure habitual and recent intake, respectively, of total dairy, cheese, cow's milk, plant-based alternative milk, and yogurt in a multi-ethnic U.S. cohort genotyped for rs4988235. Within Caucasian subjects, LP individuals reported consuming more recent total dairy and habitual total cow's milk intake. For subjects of all ethnicities, LP individuals consumed more cheese (FFQ p = 0.043, ASA24 p = 0.012) and recent total dairy (ASA24 p = 0.005). For both dietary assessments, Caucasians consumed more cheese than all non-Caucasians (FFQ p = 0.036, ASA24 p = 0.002) independent of genotype, as well as more recent intake of yogurt (ASA24 p = 0.042). LP subjects consumed more total cow's milk than LNP, but only when accounting for whether subjects were Caucasian or not (FFQ p = 0.015). Fluid milk and alternative plant-based milk consumption were not associated with genotypes or ethnicity. Our results show that both LP genotype and ethnicity influence the intake of some dairy products in a multi-ethnic U.S. cohort, but the ability of rs4988235 genotypes to predict intake may depend on ethnic background, the specific dairy product, and whether intake is reported on a habitual or recent basis. Therefore, ethnicity and the dietary assessment method should also be considered when determining the suitability of rs4988235 as a proxy for dairy intake.

Project description:BackgroundAdult lactase non-persistence (LNP) is due to low lactase expression, resulting in lactose malabsorption (LM). LNP is a genetic trait, but is typically determined by LM markers including breath H2, blood glucose, and urinary galactose after a lactose tolerance test. Known validity of these markers using milk is limited, despite being common practice. Compositional variation, such as ?-casein variants, in milk may impact diagnostic efficacy. This study aimed to evaluate the diagnostic accuracy to detect LNP using these commonly measured LM markers after both lactose and milk challenges.MethodsFourty healthy young women were challenged with 50?g lactose then randomized for separate cross-over visits to ingest 750?mL milk (37.5?g lactose) as conventional (both A1 and A2 ?-casein) and A1 ?-casein-free (a2 Milk™) milk. Blood, breath and urine were collected prior to and up to 3?h following each challenge. The presence of C/T13910 and G/A22018 polymorphisms, determined by restriction fragment length polymorphism, was used as the diagnostic reference for LNP.ResultsGenetic testing identified 14 out of 40 subjects as having LNP (C/C13910 and G/G22018). All three LM markers (breath H2, plasma glucose and urinary galactose/creatinine) discriminated between lactase persistence (LP) and LNP following lactose challenge with an area under the receiver operating characteristic (ROC) curve (AUC) of 1.00, 0.75 and 0.73, respectively. Plasma glucose and urinary galactose/creatinine were unreliable (AUC?<?0.70) after milk ingestion. The specificity of breath H2 remained high (100%) when milk was used, but sensitivity was reduced with conventional (92.9%) and a2 Milk™ (78.6%) compared to lactose (sensitivities adjusted for lactose content). The breath H2 optimal cut-off value was lower with a2 Milk™ (13?ppm) than conventional milk (21?ppm). Using existing literature cut-off values the sensitivity and specificity of breath H2 was greater than plasma glucose to detect LNP following lactose challenge whereas values obtained for urinary galactose/creatinine were lower than the existing literature cut-offs.ConclusionThis study showed accurate diagnosis of LNP by breath H2 irrespective of the substrate used, although the diagnostic threshold may vary depending on the lactose substrate or the composition of the milk.Trial registrationACTRN12616001694404 . Registered prospectively on December 9, 2016.

Dataset Information

Association of Estimated Daily Lactose Consumption, Lactase Persistence Genotype (rs4988235), and Gut Microbiota in Healthy U.S. Adults

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