Sarah Oddoux

Irritable bowel syndrome (IBS), a multifactorial intestinal disorder, is often associated with a disruption in intestinal permeability as well as an increased expression of pro-inflammatory markers. The aim of this study was to first test the impact of treatment with glutamine (Gln), a food supplement containing natural curcumin extracts and polyunsaturated n-3 fatty acids (Cur); bioactive peptides from a fish protein hydrolysate (Ga); and a probiotic mixture containing Bacillus coagulans, Lactobacillus acidophilus, Lactobacillus gasseri and Lactobacillus helveticus. These compounds were tested alone on a stress-based IBS model, the chronic-restraint stress model (CRS). The combination of Gln, Cur and Ga (GCG) was also tested. Eight-week-old C57Bl/6 male mice were exposed to restraint stress for two hours every day for four days and received different compounds every day one week before and during the CRS procedure. Plasma corticosterone levels were measured as a marker of stress, and colonic permeability was evaluated ex vivo in Ussing chambers. Changes in the gene expression of tight junction proteins (occludin, claudin-1 and ZO 1) and inflammatory cytokines (IL1β, TNFα, CXCL1 and IL10) were assessed using RT-qPCR. The CRS model led to an increase in plasma corticosterone and an increase in colonic permeability compared with unstressed animals. No change in plasma corticosterone concentrations was observed in response to CRS with the different treatments (Gln, Cur, Ga or GCG). Stressed animals treated with Gln, Cur and Ga alone and in combination showed a decrease in colonic permeability when compared to the CRS group, while the probiotic mixture resulted in an opposite response. The Ga treatment induced an increase in the expression of the anti-inflammatory cytokine IL-10, and the GCG treatment was able to decrease the expression of CXCL1, suggesting the synergistic effect of the combined mixture. In conclusion, this study demonstrated that a combined administration of glutamine, a food supplement containing curcumin and polyunsaturated n-3 fatty acids, and bioactive peptides from a fish hydrolysate was able to reduce colonic hyperpermeability and reduce the inflammatory marker CXCL1 in a stress-based model of IBS and could be of interest to patients suffering from IBS.

Anxiety is a high frequency disorder in the general population. It is usually treated with benzodiazepines, which cause side effects and a dependence that could make withdrawal difficult. Alternative treatments are therefore needed to reduce the use of anxiolytics, particularly for adjustment disorder with anxiety. An observational, multicentre, prospective, longitudinal study has been conducted by general practitioners and one gynaecologist to evaluate the efficacy of a dietary supplement on adjustment disorder with anxiety (Stress 2 study). Patients diagnosed as anxious with a score of ≥20 on the Hamilton Anxiety Rating Scale (Ham-A, first visit on Day 0 (V0)) were offered a 28-day treatment with a dietary supplement formulated with bioactive peptides from a fish protein hydrolysate (Gabolysat^®), magnesium and vitamin B6. At the second visit (V1), the Ham-A Rating Scale, the Patient Global Impression scale (PGI) and the Clinical Global Impressions scale (CGI) were administered. A 50% reduction in the Ham-A score, was achieved for 41.9% of the patients. The mean Ham-A score decreased by 12.1 ± 5.7 points (p < 0.001) between V0 (25.6 ± 3.8) and V1 (13.6 ± 6.0). Furthermore, according to the CGI scale, the anxiety of 75.3% of patients improved significantly and very significantly, with limited side effects and a negligible rebound effect. In conclusion, adjustment disorder with anxiety seems to be effectively managed by an alternative and safer solution than benzodiazepines.

Cartilage is a non-innervated and non-vascularized tissue. It is composed of one main cell type, the chondrocyte, which governs homeostasis within the cartilage tissue, but has low metabolic activity. Articular cartilage undergoes substantial stresses that lead to chondral defects, and inevitably osteoarthritis (OA) due to the low intrinsic repair capacity of cartilage. OA remains an incurable degenerative disease. In this context, several dietary supplements have shown promising results, notably in the relief of OA symptoms. In this study, we investigated the effects of collagen hydrolysates derived from fish skin (Promerim^®30 and Promerim^®60) and fish cartilage (Promerim^®40) on the phenotype and metabolism of human articular chondrocytes (HACs). First, we demonstrated the safety of Promerim^® hydrolysates on HACs cultured in monolayers. Then we showed that, Promerim^® hydrolysates can increase the HAC viability and proliferation, while decreasing HAC SA-β-galactosidase activity. To evaluate the effect of Promerim^® on a more relevant model of culture, HAC were cultured as organoids in the presence of Promerim^® hydrolysates with or without IL-1β to mimic an OA environment. In such conditions, Promerim^® hydrolysates led to a decrease in the transcript levels of some proteases that play a major role in the development of OA, such as Htra1 and metalloproteinase-1. Promerim^® hydrolysates downregulated HtrA1 protein expression. In contrast, the treatment of cartilage organoids with Promerim^® hydrolysates increased the neosynthesis of type I collagen (Promerim^®30, 40 and 60) and type II collagen isoforms (Promerim^®30 and 40), the latter being the major characteristic component of the cartilage extracellular matrix. Altogether, our results demonstrate that the use of Promerim^® hydrolysates hold promise as complementary dietary supplements in combination with the current classical treatments or as a preventive therapy to delay the occurrence of OA in humans.

A woman’s nutritional status during pregnancy and breastfeeding is not only critical for her health, but also for that of future generations. Nutritional requirements during pregnancy differ considerably from those of non-pregnant women. Thus, a personalized approach to nutritional advice is recommended. Currently, some countries recommend routine supplementation for all pregnant women, while others recommend supplements only when necessary. Maternal physiological adaptations, as well as nutritional requirements during pregnancy and lactation, will be reviewed in the literature examining the impacts of dietary changes. All of these data have been studied deeply to facilitate a discussion on dietary supplement use and the recommended doses of nutrients during pregnancy and lactation. The aim of this review is to evaluate the knowledge in the scientific literature on the current recommendations for the intake of the most common micronutrients and omega-3 fatty acids during pregnancy and lactation in the United States, Canada, and Europe. Taking into account these considerations, we examine minerals, vitamins, and omega-3 fatty acid requirements. Finally, we conclude by discussing the potential benefits of each form of supplementation.

Https://doi.org/10.18632/oncotarget.27892 Thomas Perez, Raphaël Bergès, Hélène Maccario, Sarah Oddoux, Stéphane Honoré

Articular cartilage experiences mechanical constraints leading to chondral defects that inevitably evolve into osteoarthritis (OA), because cartilage has poor intrinsic repair capacity. Although OA is an incurable degenerative disease, several dietary supplements may help improve OA outcomes. In this study, we investigated the effects of Dielen^® hydrolyzed fish collagens from skin (Promerim^®30 and Promerim^®60) and cartilage (Promerim^®40) to analyze the phenotype and metabolism of equine articular chondrocytes (eACs) cultured as organoids. Here, our findings demonstrated the absence of cytotoxicity and the beneficial effect of Promerim^® hydrolysates on eAC metabolic activity under physioxia; further, Promerim^®30 also delayed eAC senescence. To assess the effect of Promerim^® in a cartilage-like tissue, eACs were cultured as organoids under hypoxia with or without BMP-2 and/or IL-1β. In some instances, alone or in the presence of IL-1β, Promerim^®30 and Promerim^®40 increased protein synthesis of collagen types I and II, while decreasing transcript levels of proteases involved in OA pathogenesis, namely Htra1, and the metalloproteinases Mmp1-3, Adamts5, and Cox2. Both Promerim^® hydrolysates also decreased Htra1 protein amounts, particularly in inflammatory conditions. The effect of Promerim^® was enhanced under inflammatory conditions, possibly due to a decrease in the synthesis of inflammation-associated molecules. Finally, Promerim^® favored in vitro repair in a scratch wound assay through an increase in cell proliferation or migration. Altogether, these data show that Promerim^®30 and 40 hold promise as dietary supplements to relieve OA symptoms in patients and to delay OA progression.

Differentiated mammalian cells and tissues, such as skeletal muscle fibers, acquire an organization of Golgi complex and microtubules profoundly different from that in proliferating cells and still poorly understood. In adult rodent skeletal muscle, the multinucleated muscle fibers have hundreds of Golgi elements (GE), small stacks of cisternae that serve as microtubule-organizing centers. We are interested in the role of the GE in organizing a peculiar grid of microtubules located in the fiber cortex, against the sarcolemma. Modifications of this grid in the mdx mouse model of Duchenne muscular dystrophy have led to identifying dystrophin, the protein missing in both human disease and mouse model, as a microtubule guide. Compared to wild-type (WT), mdx microtubules are disordered and more dense and they have been linked to the dystrophic pathology. GE themselves are disordered in mdx. Here, to identify the causes of GE and microtubule alterations in the mdx muscle, we follow GFP-tagged microtubule markers in live mdx fibers and investigate the recovery of GE and microtubules after treatment with nocodazole. We find that mdx microtubules grow 10% faster but in 30% shorter bouts and that they begin to form a tangled network, rather than an orthogonal grid, right after nucleation from GE. Strikingly, a large fraction of microtubules in mdx muscle fibers seem to dissociate from GE after nucleation. Moreover, we report that mdx GE are mispositioned and increased in number and size. These results were replicated in WT fibers overexpressing the beta-tubulin tubb6, which is elevated in Duchenne muscular dystrophy, in mdx and in regenerating muscle. Finally, we examine the association of GE with ER exit sites and ER-to-Golgi intermediate compartment, which starts during muscle differentiation, and find it persisting in mdx and tubb6 overexpressing fibers. We conclude that GE are full, small, Golgi complexes anchored, and positioned through ER Exit Sites. We propose a model in which GE mispositioning, together with the absence of microtubule guidance due to the lack of dystrophin, determines the differences in GE and microtubule organization between WT and mdx muscle fibers.

Skeletal muscle microtubules (MTs) form a nonclassic grid-like network, which has so far been documented in static images only. We have now observed and analyzed dynamics of GFP constructs of MT and Golgi markers in single live fibers and in the whole mouse muscle in vivo. Using confocal, intravital, and superresolution microscopy, we find that muscle MTs are dynamic, growing at the typical speed of ∼9 µm/min, and forming small bundles that build a durable network. We also show that static Golgi elements, associated with the MT-organizing center proteins γ-tubulin and pericentrin, are major sites of muscle MT nucleation, in addition to the previously identified sites (i.e., nuclear membranes). These data give us a framework for understanding how muscle MTs organize and how they contribute to the pathology of muscle diseases such as Duchenne muscular dystrophy.

The terminal cisternae represent one of the functional domains of the skeletal muscle sarcoplasmic reticulum (SR). They are closely apposed to plasma membrane invaginations, the T-tubules, with which they form structures called triads. In triads, the physical interaction between the T-tubule-anchored voltage-sensing channel DHPR and the SR calcium channel RyR1 is essential because it allows the depolarization-induced calcium release that triggers muscle contraction. This interaction between DHPR and RyR1 is based on the peculiar membrane structures of both T-tubules and SR terminal cisternae. However, little is known about the molecular mechanisms governing the formation of SR terminal cisternae. We have previously shown that ablation of triadins, a family of SR transmembrane proteins interacting with RyR1, induced skeletal muscle weakness in KO mice as well as a modification of the shape of triads. Here we explore the intrinsic molecular properties of the longest triadin isoform, Trisk 95. We show that when ectopically expressed, Trisk 95 is able to modulate reticulum membrane morphology. The membrane deformations induced by Trisk 95 are accompanied by modifications of the microtubule network organization. We show that multimerization of Trisk 95 via disulfide bridges, together with interaction with microtubules, are responsible for the ability of Trisk 95 to structure reticulum membrane. When domains responsible for these molecular properties are deleted, anchoring of Trisk 95 to the triads in muscle cells is strongly decreased, suggesting that oligomers of Trisk 95 and microtubules contribute to the organization of the SR terminal cisternae in a triad.