Treatment with camu camu (Myrciaria dubia) prevents obesity by altering the gut microbiota and increasing energy expenditure in diet-induced obese mice.

OBJECTIVE: The consumption of fruits is strongly associated with better health and higher bacterial diversity in the gut microbiota (GM). Camu camu (Myrciaria dubia) is an Amazonian fruit with a unique phytochemical profile, strong antioxidant potential and purported anti-inflammatory potential. DESIGN: By using metabolic tests coupled with 16S rRNA gene-based taxonomic profiling and faecal microbial transplantation (FMT), we have assessed the effect of a crude extract of camu camu (CC) on obesity and associated immunometabolic disorders in high fat/high sucrose (HFHS)-fed mice. RESULTS: Treatment of HFHS-fed mice with CC prevented weight gain, lowered fat accumulation and blunted metabolic inflammation and endotoxaemia. CC-treated mice displayed improved glucose tolerance and insulin sensitivity and were also fully protected against hepatic steatosis. These effects were linked to increased energy expenditure and upregulation of uncoupling protein 1 mRNA expression in the brown adipose tissue (BAT) of CC-treated mice, which strongly correlated with the mRNA expression of the membrane bile acid (BA) receptor TGR5. Moreover, CC-treated mice showed altered plasma BA pool size and composition and drastic changes in the GM (eg, bloom of Akkermansia muciniphila and a strong reduction of Lactobacillus). Germ-free (GF) mice reconstituted with the GM of CC-treated mice gained less weight and displayed higher energy expenditure than GF-mice colonised with the FM of HFHS controls. CONCLUSION: Our results show that CC prevents visceral and liver fat deposition through BAT activation and increased energy expenditure, a mechanism that is dependent on the GM and linked to major changes in the BA pool size and composition.

Impact of emulsifiers for the nanoencapsulation with maltodextrin of cannabis oil by spray drying on the physicochemical properties and bioaccessibility of cannabinoids.

Our study aimed to investigate the impact of various emulsifiers, namely whey protein isolate (WPI), soy protein isolate (SPI), and Tween 80 (Tw), on their ability to encapsulate cannabis oil with maltodextrin as the wall material. The physicochemical properties of the powder, the stability of the cannabinoids, and their bioaccessibility during static in vitro digestion were examined. The average diameter of fat globules in liquid nanoemulsions was 170, 259, and 95 nm for WPI, SPI, and Tw, respectively. The encapsulation efficiency was high for protein emulsifiers (>95%) compared to Tw (∼16%). Upon powder reconstitution in water, the emulsified fat droplets remained stable for WPI (176 nm); however, higher fat globule size (diameters of 346 nm and 210 nm) was observed for SPI and Tw powders, respectively. All oil powders had high solubility (>97%). The peroxide value (PV) showed nearly a fourfold increase for the oil extracted from the powder than the initial PV of bulk oil (5.2 mEq). However, UPLC-TUV analysis of the main cannabinoids (CBD, THC, and CBN) indicated that there is no significant difference between the various formulations and the bulk oil, except for lower Tw. The in vitro digestion model results showed higher bioaccessibility of the cannabinoids for Tw (∼53%) than for proteins (WPI ∼ 7% and SPI ∼ 10%). These findings suggest that the emulsifiers used for spray drying nanoencapsulation of cannabis oil have an impact on the encapsulation efficiency and cannabinoid bioaccessibility, highlighting the importance of choosing adequate emulsifiying agents for their optimal oral delivery.

UPEC Colonic-Virulence and Urovirulence Are Blunted by Proanthocyanidins-Rich Cranberry Extract Microbial Metabolites in a Gut Model and a 3D Tissue-Engineered Urothelium.

Uropathogenic Escherichia coli (UPEC) ecology-pathophysiology from the gut reservoir to its urothelium infection site is poorly understood, resulting in equivocal benefits in the use of cranberry as prophylaxis against urinary tract infections. To add further understanding from the previous findings on PAC antiadhesive properties against UPEC, we assessed in this study the effects of proanthocyanidins (PAC) rich cranberry extract microbial metabolites on UTI89 virulence and fitness in contrasting ecological UPEC's environments. For this purpose, we developed an original model combining a colonic fermentation system (SHIME) with a dialysis cassette device enclosing UPEC and a 3D tissue-engineered urothelium. Two healthy fecal donors inoculated the colons. Dialysis cassettes containing 7log10 CFU/mL UTI89 were immersed for 2h in the SHIME colons to assess the effect of untreated (7-day control diet)/treated (14-day PAC-rich extract) metabolomes on UPEC behavior. Engineered urothelium were then infected with dialysates containing UPEC for 6 h. This work demonstrated for the first time that in the control fecal microbiota condition without added PAC, the UPEC virulence genes were activated upstream the infection site, in the gut. However, PAC microbial-derived cranberry metabolites displayed a remarkable propensity to blunt activation of genes encoding toxin, adhesin/invasins in the gut and on the urothelium, in a donor-dependent manner. Variability in subjects' gut microbiota and ensuing contrasting cranberry PAC metabolism affects UPEC virulence and should be taken into consideration when designing cranberry efficacy clinical trials. IMPORTANCE Uropathogenic Escherichia coli (UPEC) are the primary cause of recurrent urinary tract infections (UTI). The poor understanding of UPEC ecology-pathophysiology from its reservoir-the gut, to its infection site-the urothelium, partly explains the inadequate and abusive use of antibiotics to treat UTI, which leads to a dramatic upsurge in antibiotic-resistance cases. In this context, we evaluated the effect of a cranberry proanthocyanidins (PAC)-rich extract on the UPEC survival and virulence in a bipartite model of a gut microbial environment and a 3D urothelium model. We demonstrated that PAC-rich cranberry extract microbial metabolites significantly blunt activation of UPEC virulence genes at an early stage in the gut reservoir. We also showed that altered virulence in the gut affects infectivity on the urothelium in a microbiota-dependent manner. Among the possible mechanisms, we surmise that specific microbial PAC metabolites may attenuate UPEC virulence, thereby explaining the preventative, yet contentious properties of cranberry against UTI.

Influence of diet on acute endocannabinoidome mediator levels post exercise in active women, a crossover randomized study.

The extended endocannabinoid system, also termed endocannabinoidome, participates in multiple metabolic functions in health and disease. Physical activity can both have an acute and chronic impact on endocannabinoid mediators, as does diet. In this crossover randomized controlled study, we investigated the influence of diet on the peripheral response to acute maximal aerobic exercise in a sample of active adult women (n = 7) with no underlying metabolic conditions. We compared the impact of 7-day standardized Mediterranean diet (MedDiet) and control diet inspired by Canadian macronutrient intake (CanDiet) on endocannabinoidome and short-chain fatty acid metabolites post maximal aerobic exercise. Overall, plasmatic endocannabinoids, their congeners and some polyunsaturated fatty acids increased significantly post maximal aerobic exercise upon cessation of exercise and recovered their initial values within 1 h after exercise. Most N-acylethanolamines and polyunsaturated fatty acids increased directly after exercise when the participants had consumed the MedDiet, but not when they had consumed the CanDiet. This impact was different for monoacylglycerol endocannabinoid congeners, which in most cases reacted similarly to acute exercise while on the MedDiet or the CanDiet. Fecal microbiota was only minimally affected by the diet in this cohort. This study demonstrates that endocannabinoidome mediators respond to acute maximal aerobic exercise in a way that is dependent on the diet consumed in the week prior to exercise.

Feeding diversified protein sources exacerbates hepatic insulin resistance via increased gut microbial branched-chain fatty acids and mTORC1 signaling in obese mice.

Animal models of human diseases are classically fed purified diets that contain casein as the unique protein source. We show that provision of a mixed protein source mirroring that found in the western diet exacerbates diet-induced obesity and insulin resistance by potentiating hepatic mTORC1/S6K1 signaling as compared to casein alone. These effects involve alterations in gut microbiota as shown by fecal microbiota transplantation studies. The detrimental impact of the mixed protein source is also linked with early changes in microbial production of branched-chain fatty acids (BCFA) and elevated plasma and hepatic acylcarnitines, indicative of aberrant mitochondrial fatty acid oxidation. We further show that the BCFA, isobutyric and isovaleric acid, increase glucose production and activate mTORC1/S6K1 in hepatocytes. Our findings demonstrate that alteration of dietary protein source exerts a rapid and robust impact on gut microbiota and BCFA with significant consequences for the development of obesity and insulin resistance.