Human gut microbiota is an important determinant for health and disease, and recent studies emphasize the numerous factors shaping its diversity. Here we performed a genome-wide association study (GWAS) of the gut microbiota using two cohorts from northern Germany totaling 1,812 individuals. Comprehensively controlling for diet and non-genetic parameters, we identify genome-wide significant associations for overall microbial variation and individual taxa at multiple genetic loci, including the VDR gene (encoding vitamin D receptor). We observe significant shifts in the microbiota of Vdr−/− mice relative to control mice and correlations between the microbiota and serum measurements of selected bile and fatty acids in humans, including known ligands and downstream metabolites of VDR. Genome-wide significant (P < 5 × 10−8) associations at multiple additional loci identify other important points of host–microbe intersection, notably several disease susceptibility genes and sterol metabolism pathway components. Non-genetic and genetic factors each account for approximately 10% of the variation in gut microbiota, whereby individual effects are relatively small.

Our findings demonstrate that FO and KO are comparable dietary sources of n-3 PUFAs. However, when quantitatively similar doses of n-3 PUFAs are administered, KO seems to have a greater potential to promote lipid catabolism. The effect of dietary oils on the levels of inflammatory markers in hTNF-α transgenic mice fed a high-fat diet needs further investigations.

BackgroundMarine derived oils are rich in long-chain polyunsaturated omega-3 fatty acids, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have long been associated with health promoting effects such as reduced plasma lipid levels and anti-inflammatory effects. Krill oil (KO) is a novel marine oil on the market and is also rich in EPA and DHA, but the fatty acids are incorporated mainly into phospholipids (PLs) rather than triacylglycerols (TAG). This study compares the effects of fish oil (FO) and KO on gene regulation that influences plasma and liver lipids in a high fat diet mouse model.MethodsMale C57BL/6J mice were fed either a high-fat diet (HF) containing 24% (wt/wt) fat (21.3% lard and 2.3% soy oil), or the HF diet supplemented with FO (15.7% lard, 2.3% soy oil and 5.8% FO) or KO (15.6% lard, 2.3% soy oil and 5.7% KO) for 6 weeks. Total levels of cholesterol, TAG, PLs, and fatty acid composition were measured in plasma and liver. Gene regulation was investigated using quantitative PCR in liver and intestinal epithelium.ResultsPlasma cholesterol (esterified and unesterified), TAG and PLs were significantly decreased with FO. Analysis of the plasma lipoprotein particles indicated that the lipid lowering effect by FO is at least in part due to decreased very low density lipoprotein (VLDL) content in plasma with subsequent liver lipid accumulation. KO lowered plasma non-esterified fatty acids (NEFA) with a minor effect on fatty acid accumulation in the liver. In spite of a lower omega-3 fatty acid content in the KO supplemented diet, plasma and liver PLs omega-3 levels were similar in the two groups, indicating a higher bioavailability of omega-3 fatty acids from KO. KO more efficiently decreased arachidonic acid and its elongation/desaturation products in plasma and liver. FO mainly increased the expression of several genes involved in fatty acid metabolism, while KO specifically decreased the expression of genes involved in the early steps of isoprenoid/cholesterol and lipid synthesis.ConclusionsThe data show that both FO and KO promote lowering of plasma lipids and regulate lipid homeostasis, but with different efficiency and partially via different mechanisms.

KO showed protective potential against DSS colitis based on the preservation of colon length, reduction of oxidative markers and the consistent beneficial changes of HCS, cytokine, and (PG)E(3) levels, as well as PPAR-γ and Pparg1α expression compared with DSS alone. These findings indicate an anti-inflammatory and a protein antioxidant effect of KO.

Objective: To evaluate whether long-term exposure to heavy environmental pollution with polychlorinated biphenyls (PCBs) could result in impairment of thyroid status as evaluated by an epidemiological field survey. Methods: Thyroid volume (ThV) was measured by ultrasound in 238 employees of a factory (EMP) which previously produced PCBs and 454 adolescents from the surrounding area polluted by PCBs. Controls (C) were 572 adults and 965 adolescents from much less polluted areas. In the 238 EMP and various numbers (shown in parentheses) of adult C the levels of thyroid-stimulating hormone (TSH) (n ¼ 498), thyroxine (n ¼ 498), thyroglobulin (n ¼ 278) and thyroid antibodies (anti-peroxidase (TPO Ab), n ¼ 517; anti-thyroglobulin (Tg Ab), n ¼ 455; anti-TSH receptor (TSHR Ab), n ¼ 238) were estimated in serum, while only TSH and TPO Ab were measured in 269 and 171 adolescents from polluted and control areas respectively. In several subjects in whom thyroid disease was suspected, total tri-iodothyronine or free thyroxine and tri-iodothyronine were measured. In a total of 362 adults and adolescents the urinary iodine was estimated. Results: Using the Mann-Whitney test, ThV in EMP (mean Ϯ S.E. ¼ 18.85 Ϯ 0.69 ml, median ¼ 17.3 ml, upper quartile ¼ 22.9 ml, n ¼ 238) was significantly higher (P < 0.001) than that in C (13.47 Ϯ 0.48 ml, 11.5 ml, 15.3 ml, n ¼ 486 respectively). Similarly, ThV in adolescents from the polluted area (9.37 Ϯ 0.17 ml, 8.9 ml, 11.0 ml, n ¼ 454 respectively) was significantly higher (P < 0.001) than that in C (8.07 Ϯ 0.10 ml, 7.6 ml, 9.6 ml, n ¼ 965 respectively).In adults, a significantly increased prevalence of TPO Ab (P<0.05) was found (using the chi-square test) in EMP women of all ages (54/190) vs C women (70/282), in EMP women aged 31-50 years (40/117 vs 70/282 respectively) and those aged 41-50 years (28/77 vs 54/215 respectively). Compared with C, there was also a higher prevalence of Tg Ab in EMP women aged 31-60 years (36/169 vs 50/342 respectively) and of TSHR Ab (P < 0.001) in the group of EMP men and women (25/238) vs sex-and age-matched C (6/238).No difference between EMP and C was found in the level of thyroxine (mean Ϯ S.D. ¼ 116.1 Ϯ 31.2 nmol/l, n ¼ 238 vs 112.2 Ϯ 37.0 nmol/l, n ¼ 460 respectively), TSH in the range 0.1-4.5 mU/l (1.56 Ϯ 0.86 mU/l, n ¼ 219 vs 1.51 Ϯ 0.84 mU/l, n ¼ 460 respectively), prevalence of TSH >4.5 (14/238 vs 28/498 respectively) and <0.1 mU/l (5/238 vs 10/498 respectively). The prevalence of individuals without any defined clinical or laboratory signs of thyroid disorders among EMP who had worked in the factory for 21-35 years (43/128, 33.6%) was significantly lower than that in twice as many matched C (118/256, 46.1%, P < 0.025) or in EMP who had worked for only 11-20 years (36/73, 49.3%, P < 0.05).In adolescents, no difference was found in the prevalence of TPO Ab or TSH >4.5 mU/l between the polluted (17/269, 6.3% and 2/243, 0.8% respectively) and C areas (15/171, 8.5% and 4/140, 2.8% respectively). The median values of urinary iodine were in the op...