Gut microbiota and fermentation-derived branched chain hydroxy acids mediate health benefits of yogurt consumption in obese mice.

Meta-analyses suggest that yogurt consumption reduces type 2 diabetes incidence in humans, but the molecular basis of these observations remains unknown. Here we show that dietary yogurt intake preserves whole-body glucose homeostasis and prevents hepatic insulin resistance and liver steatosis in a dietary mouse model of obesity-linked type 2 diabetes. Fecal microbiota transplantation studies reveal that these effects are partly linked to the gut microbiota. We further show that yogurt intake impacts the hepatic metabolome, notably maintaining the levels of branched chain hydroxy acids (BCHA) which correlate with improved metabolic parameters. These metabolites are generated upon milk fermentation and concentrated in yogurt. Remarkably, diet-induced obesity reduces plasma and tissue BCHA levels, and this is partly prevented by dietary yogurt intake. We further show that BCHA improve insulin action on glucose metabolism in liver and muscle cells, identifying BCHA as cell-autonomous metabolic regulators and potential mediators of yogurt's health effects.

A posteriori dietary patterns better explain variations of the gut microbiome than individual markers in the American Gut Project.

BACKGROUND: Individual diet components and specific dietary regimens have been shown to impact the gut microbiome. OBJECTIVES: Here, we explored the contribution of long-term diet by searching for dietary patterns that would best associate with the gut microbiome in a population-based cohort. METHODS: Using a priori and a posteriori approaches, we constructed dietary patterns from an FFQ completed by 1800 adults in the American Gut Project. Dietary patterns were defined as groups of participants or combinations of food variables (factors) driven by criteria ranging from individual nutrients to overall diet. We associated these patterns with 16S ribosomal RNA-based gut microbiome data for a subset of 744 participants. RESULTS: Compared to individual features (e.g., fiber and protein), or to factors representing a reduced number of dietary features, 5 a posteriori dietary patterns based on food groups were best associated with gut microbiome beta diversity (P ≤ 0.0002). Two patterns followed Prudent-like diets-Plant-Based and Flexitarian-and exhibited the highest Healthy Eating Index 2010 (HEI-2010) scores. Two other patterns presented Western-like diets with a gradient in HEI-2010 scores. A fifth pattern consisted mostly of participants following an Exclusion diet (e.g., low carbohydrate). Notably, gut microbiome alpha diversity was significantly lower in the most Western pattern compared to the Flexitarian pattern (P ≤ 0.009), and the Exclusion diet pattern was associated with low relative abundance of Bifidobacterium (P ≤ 1.2 × 10-7), which was better explained by diet than health status. CONCLUSIONS: We demonstrated that global-diet a posteriori patterns were more associated with gut microbiome variations than individual dietary features among adults in the United States. These results confirm that evaluating diet as a whole is important when studying the gut microbiome. It will also facilitate the design of more personalized dietary strategies in general populations.

In silico Comparison of Test-and-Cull Protocols for Bovine Tuberculosis Control in France.

Whole depopulation of cattle herds (WHD) confirmed infected by bovine tuberculosis (bTB) has led since the 1950s to a drop of herd incidence in France below 0.1% in 2000, justifying the current officially bTB free (OTF) status of the country. However, this protocol is expensive, ethically questionable, and difficult for breeders to accept because the number of confirmed animals in an infected herd is often very low. A test-and-cull protocol combining at least three screening sessions of the entire herd followed by the slaughter of all the non-negative animals has been used for some years. The aim of this work was to evaluate in silico the epidemiological effectiveness, the public costs and the acceptability to farmers of this test-and-cull protocol as well as of several ones. A stochastic compartmental model of within-herd bTB spread was used. Six test-and-cull protocols were compared: two versions of the official protocol and four alternatives with varying delays between screenings, and varying tests used. Protocols were simulated for an average French beef herd, and compared to WHD. Three key indicators were computed: the failure probability of the protocol (a failure being defined as an herd recovering its OTF status recovery while still infected, indicator of epidemiological effectiveness), its overall public cost and the percentage of farmers who would have dropped it to switch to WHD (indicator of acceptability to farmers). Failure probability ranged from 1.4 to 12.4% and was null (by definition) for WHD. The median cost varied between 2.7 and 78 K€ for the test-and-cull protocols, vs. 120 K€ for WHD. The percentage of dropout ranged from 7.8 to 22%. The optimal tradeoff between epidemiological effectiveness, public costs, and acceptability to farmers was obtained for protocols with an increased delay (6 months instead of 2 in the currently used protocol) between the last two screening sessions, with either 3 or 2 screening sessions. This study may help improving the official test-and-cull protocol applied in France under European Union regulation, by suggesting alternative protocols, very effective, cheaper, and more acceptable than WHD.

Meta-analysis of the parasitic phase traits of Haemonchus contortus infection in sheep.

BACKGROUND: The parasitic nematode Haemonchus contortus shows highly variable life history traits. This highlights the need to have an average estimate and a quantification of the variation around it to calibrate epidemiological models. METHODS: This paper aimed to quantify the main life history traits of H. contortus and to identify explanatory factors affecting these traits using a powerful method based on a systematic review and meta-analysis of current literature. The life history traits considered are: (i) the establishment rate of ingested larvae; (ii) the adult mortality rate; (iii) the fertility (i.e. the number of eggs laid/female/day); and (iv) fecundity of female worms (i.e. the number of eggs per gram of faeces). RESULTS: A total of 37 papers that report single experimental infection with H. contortus in sheep and published from 1960 to 2015, were reviewed and collated in this meta-analysis. This encompassed 115 experiments on 982 animals. Each trait was analysed using a linear model weighted by its inverse variance. The average (± SE) larval establishment rate was 0.24 ± 0.02, which decreased as a function of the infection dose and host age. An average adult mortality rate of 0.021 ± 0.002) was estimated from the literature. This trait varied as a function of animal age, breed and protective response due to prior exposure to the parasite. Average female fertility was 1295.9 ± 280.4 eggs/female/day and decreased in resistant breeds and previously infected hosts. Average faecal egg count at necropsy was 908.5 ± 487.1 eggs per gram of faeces and varied as a function of infection duration and host resistance. The average sex ratio of H. contortus was 0.51 ± 0.006. CONCLUSION: This work is the first systematic review to summarise the available information on the parasitic phase of H. contortus in sheep. The results of the meta-analysis provide robust estimates of life history traits for parametrization of epidemiological models, their expected variation according to experimental factors, and provides correlations between these.