Warren, M. F. | Search bioRxiv

bioRxiv2024

Systems genetics approach uncovers associations between host amylase locus, gut microbiome and metabolic traits in hyperlipidemic mice

The molecular basis for how host genetic variation impacts gut microbial community and bacterial metabolic niches remain largely unknown. We leveraged 90 inbred hyperlipidemic mouse strains from the Hybrid Mouse Diversity Panel (HMDP), previously studied for a variety of cardio-metabolic traits. Metagenomic analysis of cecal DNA followed by genome-wide association analysis identified genomic loci that were associated with microbial enterotypes in the gut. Among these we detected a genetic locus surrounding multiple amylase genes that was associated with abundances of Firmicutes (Lachnospiraceae family) and Bacteroidetes (Muribaculaceae family) taxa encoding distinct starch and sugar metabolism functions. We also found that lower amylase gene number in the mouse genome was associated with higher gut Muribaculaceae levels. Previous work suggests that modulation of host amylase activity impacts the availability of carbohydrates to the host and potentially to gut bacteria. The genetic variants described above were associated with distinct gut microbial communities (enterotypes) with different predicted metabolic capacities for carbohydrate degradation. Mendelian randomization analysis revealed host phenotypes, including liver fibrosis and plasma HDL-cholesterol levels, that were associated with gut microbiome enterotypes. This work reveals novel relationships between host genetic variation, gut microbial enterotypes and host physiology/disease phenotypes in mice.

genetics↗

bioRxiv2021

Super-doses of dietary vitamin D3 intake in aged laying hens illustrates limitation of 24,25-dihydroxycholecalciferol conversion

ABSRACTO_ST_ABSBackgroundC_ST_ABSOlder humans who take high levels of vitamin D supplementation for a prolonged time may be at risk of vitamin D toxicity. It is unclear how dietary super-doses (10,000x greater than requirement) can affect vitamin D status in aged animals. Aged laying hens could be a model to compare vitamin D supplementation effects with women in peri-or postmenopausal stages of life. ObjectiveWe investigated dietary super-dose impacts of cholecalciferol (vitamin D3) on vitamin D status in aged laying hens in production. MethodsForty-eight 68 wk old Hy-Line Brown laying hens were individually housed in cages with eight hens per dietary treatment for eleven weeks. Hens were randomly assigned to one of six treatment groups of dietary vitamin D3 supplementation and fed ad libitum. Supplementation levels were 400, 800, 7,400, 14,000, 20,000, and 36,000 IU D3/kg of feed. At the end of the study, all hens were euthanized and tissue samples and feces were collected. Plasma and egg yolk vitamin D metabolites, calcium and phosphorus composition of multiple sites, and tissue gene expression levels were measured. ResultsWe observed that increasing dietary vitamin D3 increased plasma vitamin D3 and egg yolk vitamin D3 (p < 0.0001 for both sites). We also observed an increase in plasma 24,25-dihydroxycholecalciferol as dietary vitamin D3 levels increased (p < 0.0001). The plasma 25-hydroxycholecalciferol:24,25-dihydroxycholecalciferol ratio exhibited an asymptotic relationship starting at the 14,000 IU/kg D3 treatment. ConclusionsDietary super-doses of vitamin D3 led to greater plasma and egg yolk vitamin D levels to show that aged laying hens can deposit excess vitamin D in egg yolk. We suggest future research should explore how 24-hydroxylation mechanisms are affected by vitamin D supplementation. Further understanding of 24-hydroxylation can help ascertain ways to reduce risk of vitamin D toxicity.

physiology↗