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IntroductionThe reduction of nitrogen (N) and phosphorus (P) in ruminant feed is desirable due to costs and negative environmental impact. Ruminants are able to utilize N and P through endogenous recycling, particularly in times of scarcity. When N and/or P were reduced, changes in mineral homeostasis associated with modulation of renal calcitriol metabolism occurred. The aim of this study was to investigate the potential effects of dietary N- and/or P-reduction on the regulatory mechanisms of mineral transport in the kidney and its hormonal regulation in young goats.ResultsDuring N-reduction, calcium (Ca) and magnesium (Mg) concentrations in blood decreased, accompanied by a lower protein expression of cytochrome P450 family 27 subfamily B member 1 (CYP27B1) (p = 0.016). The P-reduced fed goats had low blood phosphate concentrations with simultaneously high Ca and Mg levels. The insulin-like growth factor 1 concentrations decreased significantly with P-reduction. Furthermore, gene expression of CYP27B1 (p

Abstract Background The gut microbiota has been suggested to play a significant role in the development of overweight and obesity. However, the effects of calorie restriction on gut microbiota of overweight and obese adults, especially over longer durations, are largely unexplored. Methods Here, we longitudinally analyzed the effects of intermittent calorie restriction (ICR) operationalized as the 5:2 diet versus continuous calorie restriction (CCR) on fecal microbiota of 147 overweight or obese adults in a 50-week parallel-arm randomized controlled trial, the HELENA Trial. The primary outcome of the trial was the differential effects of ICR versus CCR on gene expression in subcutaneous adipose tissue. Changes in the gut microbiome, which are the focus of this publication, were defined as exploratory endpoint of the trial. The trial comprised a 12-week intervention period, a 12-week maintenance period, and a final follow-up period of 26 weeks. Results Both diets resulted in ~5% weight loss. However, except for Lactobacillales being enriched after ICR, post-intervention microbiome composition did not significantly differ between groups. Overall weight loss was associated with significant metabolic improvements, but not with changes in the gut microbiome. Nonetheless, the abundance of the Dorea genus at baseline was moderately predictive of subsequent weight loss (AUROC of 0.74 for distinguishing the highest versus lowest weight loss quartiles). Despite the lack of consistent intervention effects on microbiome composition, significant study group-independent co-variation between gut bacterial families and metabolic biomarkers, anthropometric measures, and dietary composition was detectable. Our analysis in particular revealed associations between insulin sensitivity (HOMA-IR) and Akkermansiaceae, Christensenellaceae, and Tanerellaceae. It also suggests the possibility of a beneficial modulation of the latter two intestinal taxa by a diet high in vegetables and fiber, and low in processed meat. Conclusions Overall, our results suggest that the gut microbiome remains stable and highly individual-specific under dietary calorie restriction. Trial registration The trial, including the present microbiome component, was prospectively registered at ClinicalTrials.gov NCT02449148 on May 20, 2015.

Tachysterol2 (T2) is a photoisomer of the previtamin D2 found in UV-B-irradiated foods such as mushrooms or baker’s yeast. Due to its structural similarity to vitamin D, we hypothesized that T2 can affect vitamin D metabolism and in turn, fibroblast growth factor 23 (FGF23), a bone-derived phosphaturic hormone that is transcriptionally regulated by the vitamin D receptor (VDR). Initially, a mouse study was conducted to investigate the bioavailability of T2 and its impact on vitamin D metabolism and Fgf23 expression. UMR106 and IDG-SW3 bone cell lines were used to elucidate the effect of T2 on FGF23 synthesis and the corresponding mechanisms. LC-MS/MS analysis found high concentrations of T2 in tissues and plasma of mice fed 4 vs. 0 mg/kg T2 for 2 weeks, accompanied by a significant decrease in plasma 1,25(OH)2D and increased renal Cyp24a1 mRNA abundance. The Fgf23 mRNA abundance in bones of mice fed T2 was moderately higher than that in control mice. The expression of Fgf23 strongly increased in UMR106 cells treated with T2. After Vdr silencing, the T2 effect on Fgf23 diminished. This effect is presumably mediated by single-hydroxylated T2-derivatives, since siRNA-mediated silencing of Cyp27a1, but not Cyp27b1, resulted in a marked reduction in T2-induced Fgf23 gene expression. To conclude, T2 is a potent regulator of Fgf23 synthesis in bone and activates Vdr. This effect depends, at least in part, on the action of Cyp27a1. The potential of oral T2 to modulate vitamin D metabolism and FGF23 synthesis raises questions about the safety of UV-B-treated foods.