Probiotic interventions promote metabolic health in high fat-fed hamsters in association with gut microbiota and endocannabinoidome alterations.

Probiotics represent a promising tool to improve metabolic health, including lipid profiles and cholesterol levels. Modulation of the gut microbiome and the endocannabinoidome - two interrelated systems involved in several metabolic processes influenced by probiotics - has been proposed as a potential mechanism of action. This study establishes the impact of probiotics on metabolic health, gut microbiota composition and endocannabinoidome mediators in an animal model of hypercholesterolaemia. Syrian hamsters were fed either a low-fat low-cholesterol or high-fat high-cholesterol (HFHC) diet to induce hypercholesterolaemia and gavaged for 6 weeks with either Lactobacillus acidophilus CL1285, Lactiplantibacillus plantarum CHOL-200 or a combination of the two. Globally, probiotic interventions ameliorated, at least partially, lipid metabolism in HFHC-fed hamsters. The interventions, especially those including L. acidophilus, modified the gut microbiota composition of the small intestine and caecum in ways suggesting reversal of HFHC-induced dysbiosis. Several associations were observed between changes in gut microbiota composition and endocannabinoidome mediators following probiotic interventions and both systems were also associated with improved metabolic health parameters. For instance, potential connexions between the Eubacteriaceae and Deferribacteraceae families, levels of 2­palmitoylglycerol, 2­oleoylglycerol, 2­linoleoylglycerol or 2­eicosapentaenoylglycerol and improved lipid profiles were found. Altogether, our results suggest a potential crosstalk between gut microbiota and the endocannabinoidome in driving metabolic benefits associated with probiotics, especially those including L. acidophilus, in an animal model of hypercholesterolaemia.

Endocannabinoids as endometrial inflammatory markers in lactating Holstein cows.

The objective of this study was to consider endocannabinoid system as inflammatory markers in bovine endometrium to better understand the role of this system in regulating many of the functions that are related to inflammatory condition. At day 26 post-partum, fourteen cows were divided into two groups depending on the inflammatory condition: 1- subclinical endometritis (n = 7, with purulent or mucopurulent uterine discharge detectable in the vagina) and 2- healthy (n = 7, No (muco)) purulent discharge. Blood samples were collected at 26 and 30 days relative to calving to determine plasma tumour necrosis factor (TNF) and lipopolysaccharide-binding protein (LBP) concentrations; moreover, uterine biopsy was carried out on day 26 post-partum to measure mRNA abundance of TNF, interleukin-1B (IL1B), interleukin-6 (IL-6), C-X-C motif chemokine ligand 8 (CXCL8), endocannabinoid receptor (CNR2), N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA) and monoglyceride lipase (MGLL) by real-time PCR. Results showed mean plasma concentrations of TNF and LBP were lower in healthy cows compared to subclinical endometritis cows (p < .05). Relative mRNA expression for NAAA and FAAH was decreased (p < .05), and relative mRNA expression for CNR2 and NAPEPLD increased in cows with subclinical endometritis compared to healthy cows. In conclusion, relative mRNA expression of TNF, IL1B and CXCL8 and plasma concentration of LBP increased during inflammatory condition along with decreased endocannabinoids hydrolyzing enzyme (NAAA and FAAH), increased enzymes that synthesize endocannabinoids (NAPEPLD) and relative gene expression of the endocannabinoid receptor; together, these contribute to increased endocannabinoids levels during inflammation. Overall, we provide evidence that endocannabinoid system is altered in endometrium tissue during inflammation through increased mRNA expression of CNR2 and synthesis enzyme and decreased mRNA expression of hydrolyzing enzymes interfere with pro-cytokine production and signalling, which may interfere with the onset and progression of inflammation.

Dietary conjugated linoleic acid supplementation alters the expression of genes involved in the endocannabinoid system in the bovine endometrium and increases plasma progesterone concentrations.

Endocannabinoids are derived from phospholipids and reduce fertility by interfering with implantation. Identification of changes in the expression of genes of the endocannabinoid system as a result of dietary inclusion of conjugated linoleic acid (CLA) is critical to the advancement of our understanding of the nutritional regulation of uterine function. An experiment was conducted on transition cows to evaluate the expression of key endocannabinoid genes in bovine endometrium in response to dietary supplementation with CLA. A total of 16 cows were randomly assigned to two treatments: (1) control (75 g/day palm oil) and (2) CLA (75 g/day CLA) from 21 days prepartum to Day 42 postpartum. Cows underwent uterine biopsy on days 21 and 42 postpartum. The abundance of mRNA encoding endocannabinoid receptor (CNR2), N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and monoglyceride lipase (MGLL) was measured by real-time PCR. Results reported that relative levels of mRNA encoding CNR2 and NAPEPLD were decreased (P < 0.05) compared with control cows between Days 21 and 42 postpartum. Relative levels of mRNA coding for NAAA and MGLL were not different (P > 0.05) in the same situation. Mean plasma progesterone concentrations were higher in CLA-fed cows compared with control cows at Day 42 postpartum (3.51 and 1.42 ng/mL, respectively, P < 0.05). In conclusion, we suggest that the beneficial effects of a diet enriched with CLA are the result of a decrease in relative gene expression of the endocannabinoid receptor (CNR2) and enzymes that synthesize fatty acid amides (NAPEPLD) and of an increase in the expression of PTGS2 that in turn can oxidate endocannabinoids and consequently resulted in increased plasma progesterone concentrations during early lactation.