Impact of a Whey Protein Hydrolysate Treated by Electrodialysis with Ultrafiltration Membrane on the Development of Metabolic Syndrome and the Modulation of Gut Microbiota in Mice.

The development of Metabolic Syndrome (MetS) affects a large number of people around the world and represents a major issue in the field of health. Thus, it is important to implement new strategies to reduce its prevalence, and various approaches are currently under development. Recently, an eco-friendly technology named electrodialysis with ultrafiltration membrane (EDUF) was used successfully for the first time at a semi-industrial scale to produce three fractions concentrated in bioactive peptides (BPs) from an enzymatically hydrolyzed whey protein concentrate (WPC): the initial (F1), the final (F2) and the recovery fraction (F3), and it was demonstrated in vitro that F3 exhibited interesting DPP-IV inhibitory effects. Therefore, the present study aimed to evaluate the effect of each fraction on in vivo models of obesity. A daily dose of 312.5 mg/kg was administered to High Fat/High Sucrose diet (HFHS) induced C57BL6/J mice for eight weeks. The physiological parameters of each group and alterations of their gut microbiota by the fractions were assessed. Little effect of the different fractions was demonstrated on the physiological state of the mice, probably due to the digestion process of the BP content. However, there were changes in the gut microbiota composition and functions of mice treated with F3.

The Concentration of Organic Acids in Cranberry Juice Modulates the Gut Microbiota in Mice.

A daily consumption of cranberry juice (CJ) is linked to many beneficial health effects due to its richness in polyphenols but could also awake some intestinal discomforts due to its organic acid content and possibly lead to intestinal inflammation. Additionally, the impact of such a juice on the gut microbiota is still unknown. Thus, this study aimed to determine the impacts of a daily consumption of CJ and its successive deacidification on the intestinal inflammation and on the gut microbiota in mice. Four deacidified CJs (DCJs) (deacidification rates of 0, 40, 60, and 80%) were produced by electrodialysis with bipolar membrane (EDBM) and administered to C57BL/6J mice for four weeks, while the diet (CHOW) and the water were ad libitum. Different parameters were measured to determine intestinal inflammation when the gut microbiota was profiled. Treatment with a 0% DCJ did not induce intestinal inflammation but increased the gut microbiota diversity and induced a modulation of its functions in comparison with control (water). The effect of the removal of the organic acid content of CJ on the decrease of intestinal inflammation could not be observed. However, deacidification by EDBM of CJ induced an additional increase, in comparison with a 0% DCJ, in the Lachnospiraceae family which have beneficial effects and functions associated with protection of the intestine: the lower the organic acid content, the more bacteria of the Lachnospiraceae family and functions having a positive impact on the gut microbiota.

Evolution of cranberry juice compounds during in vitro digestion and identification of the organic acid responsible for the disruption of in vitro intestinal cell barrier integrity.

Cranberry juice is increasingly consumed for its richness in polyphenols having a positive impact on human health. Unfortunately, when regularly consumed, its high concentration in organic acids may cause some intestinal discomforts. In the present study, its organic acid content was reduced of 41% by electrodialysis with bipolar membrane (EDBM), and the resulted deacidified juice was divided in five different juices readjusted or not with different concentrations of citric and/or malic acid(s) corresponding to the concentration of this/these acid(s) recovered during EDBM or at the titratable acidity (TA) of the non-deacidified cranberry juice. The evolution of the cranberry juice main interesting compounds (organic acids and polyphenols), according to the concentration and nature of the organic acids present, was studied for the first time at each specific stages of the digestion. After digestion, Caco-2 cells were exposed to all digested juices to identify the organic acid(s) responsible for the loss of integrity of the epithelial barrier. It appeared that organic acid contents did not change during the different steps of the digestion while polyphenolic compounds decreased starting from the gastric phase. Whatever the organic acid concentration or nature, the concentration of PACs significantly decreased between the salivary and the gastric steps but was different according to their structure when the concentration of most of anthocyanins significantly decreased at the gastric step. Also, to the best of our knowledge, it was the first time that citric acid was demonstrated as the organic acid responsible for the loss of integrity of Caco-2 cell monolayers.

Caveolae-mediated effects of TNF-α on human skeletal muscle cells.

Chronic diseases are characterized by the production of pro-inflammatory cytokines such than TNF-α and are frequently correlated with muscle wasting conditions. Among the pleiotropic effects of TNF-α within the cell, its binding to TNFR1 receptor has been shown to activate sphingomyelinases leading to the production of ceramides. Sphingomyelinases and TNF receptor have been localized within caveolae which are specialized RAFT enriched in cholesterol and sphingolipids. Because of their inverted omega shape, maintained by the oligomerization of specialized proteins, caveolins and cavins, caveolae serve as membrane reservoir therefore providing mechanical protection to plasma membranes. Although sphingolipids metabolites, caveolins and TNF-α/TNFR1 have been shown to independently interfere with muscle physiology, no data have clearly demonstrated their concerted action on muscle cell regeneration. In this context, our study aimed at studying the molecular mechanisms induced by TNF-α at the level of caveolae in LHCN-M2 human muscle satellite cells. Here we showed that TNF-α-induced production of ROS and nSMase activation requires caveolin. More strikingly, we have demonstrated that TNF-α induces the formation of additional caveolae at the plasma membrane of myoblasts. Furthermore, TNF-α prevents myoblast fusion suggesting that inflammation could modulate caveolae organization/function and satellite cell function.