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International audience; Avocado peel, a byproduct from the avocado pulp industry, is a promising source of polyphenolic compounds. We evaluated the effect of a proanthocyanidin-rich avocado peel polyphenol extract (AvPPE) on the composition and metabolic activity of human fecal microbiota cultured for 24 h in a bioreactor in the presence of high protein (HP) amounts and the effect of the resulting culture supernatants (CSs) on HT-29Glc(-/+) and Caco-2 cells. AvPPE decreased the HP-induced production of ammonia, H2S, propionate, and isovalerate and increased that of indole and butyrate. Microbiota composition was marginally affected by HP, whileAvPPE increased the microorganisms/abundance of phylum Actinobacteria, families Coriobacteriaceae and Ruminococcaceae, and genus Faecalibacterium. AvPPE failed to prevent the HP-induced decrease of HT-29Glc(-/+) cell viability and energy efficiency but prevented the HP-induced alterations of barrier function in Caco-2 cells. Additionally, the genotoxic effect of the CSs upon HT-29Glc(-/+) was attenuated by AvPPE. Therefore, AvPPE may be considered as a promising product for improving colonic homeostasis.

Obesity is a worldwide epidemic, which is characterized by the excess accumulation of adipose tissue and to an extent that impairs both the physical and psychosocial health and well-being. There are several weight-loss strategies available, including dietary modification, pharmacotherapy, and bariatric surgery, but many are ineffective or not a long-term solution. Bioactive compounds present in medicinal plants and plant extracts, like polyphenols, constitute the oldest and most extensive form of alternative treatments for the prevention and management of obesity. Their consumption is currently increasing in the population due to the high cost, potential adverse effects, and limited benefits of the currently available pharmaceutical drugs. A great number of studies has explored how dietary polyphenols can interfere with the different mechanisms associated with obesity development. They suggest that these compounds can decrease energy and food intake, lipogenesis, and preadipocyte differentiation and proliferation, while increasing energy expenditure, lipolysis, and fat oxidation. Both quercetin, one of the most common dietary flavonols in the western diet, and epigallocatechin gallate (EGCG), the most abundant polyphenol in green tea, exhibit antiobesity effects in adipocyte cultures and animal models. However, the extrapolation of these potential benefits to obese humans remains unclear. Although quercetin supplementation does not seem to exert any beneficial effects on body weight, this polyphenol could prevent the obesity-associated mortality by reducing cardiovascular disease risk. An important consideration for the design of further trials is the occurrence of gene polymorphisms in key enzymes involved in flavanol metabolism, which determines a subject's sensitivity to catechins and seems, therefore, crucial for the success of the antiobesity intervention. Although the evidence supporting antiobesity effects is more consistent in EGCG than with quercetin studies, they could still be beneficial by reducing the cardiovascular risk of obese subjects, rather than inducing body weight loss.

International audience; The consumption of high-protein diets (HPDs) increases the flux of undigested proteins moving to the colon. These proteins are hydrolyzed by bacterial proteases and peptidases, releasing amino acids, which in turn are metabolized by the intestinal microbiota (IM) for protein synthesis and production of various metabolites that can exert positive or deleterious effects, depending on their concentrations, at the colonic or systemic level. On the other hand, proanthocyanidins are polymers of flavan-3-ols which cannot be absorbed at the intestinal level, accumulating in the colon where they are fermented by the IM producing metabolites that appear beneficial for colonocytes and also at the peripheral level. This study evaluated the effect of an avocado peel polyphenol extract (AvPPE) rich in proanthocyanidins on the production of cecal bacterial metabolites and microbiota composition in rats fed a HPD. Compared with the normal-protein (NP) group, HPD did not markedly affect the body weight gain of the animals, but increased the kidney weight. Additionally, the HPD induced a higher cecal concentration of ammonia (NH4+/NH3), hydrogen sulfide (H2S) and branched-chain fatty acids (BCFAs). The supplementation with AvPPE attenuated the production of H2S and increased the production of indole. On the other hand, the HPD affected the composition of the cecal microbiota, increasing the relative abundance of the genera Bacteroides and Lactobacillus, while decreasing Prevotella. The AvPPE counteracted the increase induced by the HPD on the genus Lactobacillus, and increased the relative abundance of [Prevotella]. Our results contribute towards explaining the health-promoting effects of proanthocyanidin-rich dietary foodstuffs including fruits and vegetables.

International audience; Hydrogen sulfide (H2S), a metabolic end product synthesized by the microbiota from l-cysteine, has been shown to act at low micromolar concentration as a mineral oxidative substrate in colonocytes while acting as an inhibitor of oxygen consumption at higher luminal concentrations (65 mu M and above). From the previous works showing that polyphenols can bind volatile sulfur compounds, we hypothesized that different dietary proanthocyanidin-containing polyphenol (PACs) plant extracts might modulate the inhibitory effect of H2S on colonocyte respiration. Using the model of human HT-29 Glc-/+ cell colonocytes, we show here that pre-incubation of 65 mu M of the H2S donor NaHS with the different polyphenol extracts markedly reduced the inhibitory effect of NaHS on colonocyte oxygen consumption. Our studies on HT-29 Glc-/+ cell respiration performed in the absence or the presence of PACs reveal rapid binding of H2S with the sulfide-oxidizing unit and slower binding of H2S to the cytochrome c oxidase (complex IV of the respiratory chain). Despite acute inhibition of colonocyte respiration, no measurable effect of NaHS on paracellular permeability was recorded after 24 h treatment using the Caco-2 colonocyte monolayer model. The results are discussed in the context of the binding of excessive bacterial metabolites by unabsorbed dietary compounds and of the capacity of colonocytes to adapt to changing luminal environment.

Proanthocyanidins (PACs) are polymers of flavan-3-ols abundant in many vegetable foods and beverages widely consumed in the human diet. There is increasing evidence supporting the beneficial impact of dietary PACs in the prevention and nutritional management of non-communicable chronic diseases. It is considered that PACs with a degree of polymerization > 3 remain unabsorbed in the gastrointestinal tract and accumulate in the colonic lumen. Accordingly, the gastrointestinal tract may be considered as a key organ for the healthy-promoting effects of dietary PACs. PACs form non-specific complexes with salivary proteins in mouth, originating the sensation of astringency, and with dietary proteins, pancreatic enzymes and nutrient transporters in the intestinal lumen, decreasing the digestion and absorption of carbohydrates, proteins and lipids. They also exert anti-microbial activities, interfering with cariogenic or ulcerogenic pathogens in the mouth (Streptococcus mutans) and stomach (Helicobacter pylori), respectively. Through their anti-oxidant and anti-inflammatory properties, PACs decrease inflammatory processes in animal model of gastric and colonic inflammation. Interestingly, they exert prebiotic activities, stimulating the growth of Lactobacillus spp. and Bifidobacterium spp. as well as some butyrate-producing bacteria in the colon. Finally, PACs are also metabolized by the gut microbiota, producing metabolites, mainly aromatic acids and valerolactones, which accumulate in the colon and/or are absorbed into the bloodstream. Accordingly, these compounds could display biological activities on the colonic epithelium or in extra-intestinal tissues and, therefore, contribute to part of the beneficial effects of dietary PACs.

WOS:000375969100012; International audience; The protective effect of proanthocyanidin-containing polyphenol extracts from apples, avocados, cranberries, grapes, or proanthocyanidin microbial metabolites was evaluated in colonic epithelial cells exposed to p-cresol, a deleterious compound produced by the colonic microbiota from L-tyrosine. In HT29 Glc(-/+) cells, p-cresol significantly increased LDH leakage and decreased ATP contents, whereas in Caco-2 cell monolayers, it significantly decreased the transepithelial electrical resistance and increased the paracellular transport of FITC-dextran. The alterations induced by p-cresol in HT29 Glc(-/+) cells were prevented by the extracts from cranberries and avocados, whereas they became worse by extracts from apples and grapes. The proanthocyanidin bacterial metabolites decreased LDH leakage, ameliorating cell viability without improving intracellular ATP. All of the polyphenol extracts and proanthocyanidin bacterial metabolites prevented the p-cresol-induced alterations of barrier function. These results suggest that proanthocyanidin-containing polyphenol extracts and proanthocyanidin metabolites likely contribute to the protection of the colonic mucosa against the deleterious effects of p-cresol.