Sex-dependent effects of a high fat diet on metabolic disorders, intestinal barrier function and gut microbiota in mouse.

Obesity is often associated with sex-dependent metabolic complications, in which altered intestinal barrier function and gut microbiota contribute. We aimed to characterize in mice the sex-dependent effects of a high fat diet on these parameters. Male and female C57BL/6 mice received a standard (SD) or high fat diet (HFD; 60% kcal from fat) during 14 weeks (W14). Body composition, glucose tolerance, insulin sensitivity, intestinal permeability, colonic expression of 44 genes encoding factors involved in inflammatory response and gut barrier function, cecal microbiota, plasma adipokines and white adipose tissue response have been assessed. Both male and female HFD mice exhibited an increase of body weight and fat mass gain and glucose intolerance compared to SD mice. However, only male HFD mice tended to develop insulin resistance associated to increased Tnfα and Ccl2 mRNA expression in perigonadal adipose tissue. By contrast, only female HFD mice showed significant intestinal hyperpermeability that was associated with more markedly altered colonic inflammatory response. Cecal microbiota richness was markedly reduced in both sexes (Observed species) with sex-dependent modifications at the phyla or family level, e.g. decreased relative abundance of Bacillota and Lachnospiraceae in females, increased of Bacteroidaceae in males. Interestingly, some of these microbiota alterations were correlated with peripheral metabolic and inflammatory markers. In conclusions, male and female mice exhibit different responses to a high fat diet with specific changes of gut microbiota, intestinal barrier function, colonic and white adipose tissue inflammation, metabolic markers and body weight gain. The underlying mechanisms should be deciphered in further investigations.

Effects of repetitive transcranial magnetic stimulation of the right inferior parietal lobe on the body image perception in anorexia nervosa: A pilot randomized controlled study.

INTRODUCTION: Restrictive anorexia nervosa (AN) is associated with distorted perception of body shape, previously linked to hypoactivity and reduced excitability of the right inferior parietal lobe (rIPL). Here, we investigated the impact of high-frequency repetitive transcranial magnetic stimulation (HF rTMS) of the rIPL on body shape perception in patients with AN. METHODS: Seventeen patients with AN (median [Q1_Q3] age, 35 [27_39] years; disease duration, 12 [6_18] years) were randomly assigned to receive real or sham HF (10 Hz) rTMS of the rIPL over a period of 2 weeks, comprising 10 sessions. The primary outcome measure was the Body Shape Questionnaire (BSQ). Secondary outcomes included eating disorder symptoms, body mass index, mood, anxiety, and safety. Data collection were done at baseline, post-rTMS, and at 2 weeks and 3 months post-rTMS. RESULTS: Following both real and sham rTMS of the rIPL, no significant differences were observed in body shape perception or other parameters. Both real and sham rTMS interventions were deemed safe and well tolerated. Notably, serious adverse events were associated with the underlying eating and mood disorders, resulting in hospitalization for undernutrition (five patients) or suicidal attempts (two patients). CONCLUSION: This pilot study does not support the use of rTMS of the rIPL as an effective method for improving body shape perception in individuals with the restrictive form of AN. Further research is warranted to comprehensively explore both the clinical and neurophysiological effects of HF rTMS in this population.

Does so-called "healthy" content on instagram display balanced recipes? A pilot study in relation to the risk of unhealthy eating patterns in social network users.

OBJECTIVE: social networks (SN) including Instagram have increased in popularity. However, SN-mediated content may influence eating behaviors in a negative way. This study analyzed whether Instagram content claimed as "healthy" complies with nutritional guidelines. METHODS: recipes posted in French on Instagram with the caption #healthy or similar ones were analyzed, once from February to May 2023 and again in April 2024. Health authorities' guidelines and food pyramid inclusion criteria were used for the quantitative and qualitative analysis, respectively. Recipes were then classified as balanced, partially unbalanced or unbalanced, with the two subgroups "restrictive" and "excessive", and according to the main protein source. RESULTS: we coded a total of 114 courses (2 datasets of 57 courses each). Among these, 3 were classified as balanced main courses, 45 as partially unbalanced main courses and 66 as unbalanced main courses (21 were deemed as restrictive, 21 as excessive and 24 were otherwise inadequate), with a majority of hypocaloric courses. Approximately half of the recipes were vegetarian or vegan. DISCUSSION: these results suggest that food recipes published on Instagram as #healthy may, at times, be far from nutritional guidelines and could rather promote unbalanced eating patterns. This suggest that food-related content on SN might be insufficiently moderated and that recipes referenced as #healthy should perhaps be accompanied by warnings and preventive measures. This observation, in addition to other detrimental behaviors displayed on SN (e.g. extreme physical activity or body image pressure) may contribute to the increased incidence of eating disorders (ED) associated with problematic SN use. Alerts on this risk and accessible tools for the prevention and early detection of ED risk in SN users are urgently needed.

Analysis of feeding and eating disorders in 191 children according to psychiatric or gastroenterological recruitment: The PEDIAFED cohort study.

OBJECTIVE: The DSM-5 classification introduced new Feeding and Eating Disorders (FED) diagnostic categories, notably Avoidant and Restrictive Food Intake Disorder (ARFID), which, like other FED, can present psychiatric and gastrointestinal symptoms. However, paediatric clinical research that focuses on children below the age of 12 years remains scarce. The aim of this study was first to investigate the clinical features of FED in a cohort of children, second to compare them according to their recruitment (gastroenterology or psychiatry unit). METHOD: This non-interventional retrospective cohort study analysed 191 patients in a French paediatric tertiary care centre (gastroenterology n = 100, psychiatry n = 91). The main outcome variables were clinical data (type of FED, BMI, nutritional support, chronic diseases, psychiatric comorbidities, sensory, sleep, language disorders, gastrointestinal complaints, adverse life events, family history). The outcome was defined by a Clinical Global Impression of Change-score. RESULTS: FED diagnoses were ARFID (n = 100), Unspecified FED (UFED, n = 57), anorexia nervosa (AN, n = 33) and one pica/rumination. Mean follow-up was 3.28 years (SD 1.91). ARFID was associated with selective and sensory disorders (p < 0.001); they had more anxiety disorders than patients with UFED (p < 0.001). Patients with UFED had more chewing difficulties, language disorder (p < 0.001), and more FED related to chronic disease (p < 0.05) than patients with ARFID and AN. Patients with AN were female, underweight, referred exclusively to the psychiatrist, and had more depression than patients with ARFID and UFED (p < 0.001). The gastroenterology cohort included more UFED, while the psychiatry cohort included more psychiatric comorbidities (p < 0.001). A worse clinical outcome was associated with ARFID, a younger age at onset (p < 0.001), selective/sensory disorders and nutritional support (p < 0.05). CONCLUSION: ARFID and UFED children were diagnosed either by gastroenterologists or psychiatrists. Due to frequently associated somatic and psychiatric comorbidities, children with FED should benefit from a multidisciplinary assessment and care.

Novel dietary strategies to manage sarcopenia.

PURPOSE OF REVIEW: Sarcopenia is a wasting disease, mostly age-related in which muscle strength and mass decline, such as physical performance. With aging, both lower dietary protein intake and anabolic resistance lead to sarcopenia. Moreover, aging and sarcopenia display low-grade inflammation, which also worsen muscle condition. In this review, we focused on these two main targets to study dietary strategies. RECENT FINDINGS: The better understanding in mechanisms involved in sarcopenia helps building combined dietary approaches including physical activity that would slow the disease progression. New approaches include better understanding in the choice of quality proteins, their amount and schedule and the association with antioxidative nutrients. SUMMARY: First, anabolic resistance can be countered by increasing significantly protein intake. If increasing amount remains insufficient, the evenly delivery protein schedule provides interesting results on muscle strength. Quality of protein is also to consider for decreasing risk for sarcopenia, because varying sources of proteins appears relevant with increasing plant-based proteins ratio. Although new techniques have been developed, as plant-based proteins display a lower availability, we need to ensure an adapted overall amount of proteins. Finally, specific enrichment with leucine from whey protein remains the dietary combined approach most studied and studies on citrulline provide interesting results. As cofactor at the edge between anabolic and antioxidative properties, vitamin D supplementation is to recommend. Antioxidative dietary strategies include both fibers, vitamins, micronutrients and polyphenols from various sources for positive effects on physical performance. The ω 3 -polyunsaturated fatty acids also display positive modifications on body composition. Gut microbiota modifiers, such as prebiotics, are promising pathways to improve muscle mass and function and body composition in sarcopenic patients. Nutritional interventions could be enhanced by combination with physical activity on sarcopenia. In healthy older adults, promoting change in lifestyle to get near a Mediterranean diet could be one of the best options. In sarcopenia adults in which lifestyle changes appears unprobable, specific enrichement potentialized with physical activity will help in the struggle against sarcopenia. Longitudinal data are lacking, which makes it hard to draw strong conclusions. However, the effects of a physical activity combined with a set of nutrition interventions on sarcopenia seems promising.

Sex-dependent circadian alterations of both central and peripheral clock genes expression and gut-microbiota composition during activity-based anorexia in mice.

RATIONALE: Patients with anorexia nervosa (AN) often present sleep disorders and circadian hormonal dysregulation. The role of the microbiota-gut-brain axis in the regulation of feeding behavior has emerged during the last decades but its relationships with the circadian rhythm remains poorly documented. Thus, we aimed to characterize the circadian clock genes expression in peripheral and central tissues in the activity-based anorexia mouse model (ABA), as well as the dynamics of the gut-microbiota composition. METHODS: From day 1 to day 17, male and female C57Bl/6 mice were submitted or not to the ABA protocol (ABA and control (CT) groups), which combines a progressive limited access to food and a free access to a running wheel. At day 17, fasted CT and ABA mice were euthanized after either resting (EoR) or activity (EoA) phase (n = 10-12 per group). Circadian clock genes expression was assessed by RT-qPCR on peripheral (liver, colon and ileum) and central (hypothalamic suprachiasmatic nucleus or SCN) tissues. Cecal bacterial taxa abundances were evaluated by qPCR. Data were compared by two-way ANOVA followed by post-tests. RESULTS: ABA mice exhibited a lower food intake, a body weight loss and an increase of diurnal physical activity that differ according with the sex. Interestingly, in the SCN, only ABA female mice exhibited altered circadian clock genes expression (Bmal1, Per1, Per2, Cry1, Cry2). In the intestinal tract, modification of clock genes expression was also more marked in females compared to males. For instance, in the ileum, female mice showed alteration of Bmal1, Clock, Per1, Per2, Cry1, Cry2 and Rev-erbα mRNA levels, while only Per2 and Cry1 mRNAs were affected by ABA model in males. By contrast, in the liver, clock genes expression was more markedly affected in males compared to females in response to ABA. Finally, circadian variations of gut-bacteria abundances were observed in both male and female mice and sex-dependent alteration were observed in response to the ABA model. CONCLUSIONS: This study shows that alteration of circadian clock genes expression at both peripheral and central levels occurs in response to the ABA model. In addition, our data underline that circadian variations of the gut-microbiota composition are sex-dependent.

Anorexia nervosa is an eating disorder with a female predominance. However, the underlying pathophysiological mechanisms are still incompletely understood. Patients with anorexia nervosa often show alterations in circadian rhythm, including sleep disorders and modifications in hormone circadian rhythm. The circadian rhythm is controlled in the central nervous system, particularly in the suprachiasmatic nucleus, but clocks have also been described in peripheral tissues. To better understand the putative role of circadian rhythm in the pathophysiology of anorexia nervosa, we have conducted an experimental study in a rodent model of anorexia nervosa called "activity-based anorexia" on both males and females. Interestingly, we observed that the expression of genes involved in the circadian rhythm is affected by the activity-based anorexia model in both the suprachiasmatic nucleus and peripheral tissues, such as the small intestine and liver. In addition, gut­microbiota also shows circadian variation. Interestingly, the anorexia-induced alterations of circadian variations (clock genes expression and gut­microbiota composition) are sex- and tissue-dependent. For instance, female mice exhibited more marked alterations in the ileum, whereas, in males, modifications were more pronounced in the liver. This study highlights sex-dependent alterations of circadian clock genes expression and of gut­microbiota in response to the anorexia rodent model. Further experiments should be performed to investigate the contribution of these mechanisms in the etiology of anorexia nervosa and the higher prevalence in females.

Single-Donor and Pooling Strategies for Fecal Microbiota Transfer Product Preparation in Ulcerative Colitis: A Systematic Review and Meta-analysis.

INTRODUCTION: Patients with ulcerative colitis (UC) have a less diverse microbiome than healthy subjects. Multiple studies have evaluated fecal microbiota transfer (FMT) in these patients using different methods of product preparation, doses, and routes of administration. A systematic review and meta-analysis was performed to compare the efficacy of single-donor (SDN) and multidonor (MDN) strategies for product preparation. METHODS: Systematic searches were performed in Web of Science, Scopus, PubMed, and Orbit Intelligence for studies comparing FMT products manufactured using SDN or MDN strategies to placebo in patients with UC. Fourteen controlled studies were selected for meta-analysis (10 randomized and 4 nonrandomized). The treatment response was assessed by using fixed- and random-effects models, and the significance of the indirect difference between the interventions was assessed using a network approach. RESULTS: Considering all 14 studies, MDN and SDN were superior to placebo in terms of treatment response (risk ratios [RRs]: 4.41 and 1.57, respectively [P ≤ 0.001 for both]), and MDN was superior to SDN (RR: 2.81, P = 0.005). Meta-analysis of the 10 studies with high quality of evidence showed that MDN was superior to SDN in terms of treatment response (RR: 2.31, P = 0.042). Results were identical for both models. DISCUSSION: There was a significant clinical benefit (remission) for patients with UC who received FMT with products manufactured by MDN strategies. Reduction of donor effect may lead to a gain in microbial diversity that could improve response to treatment. These results may have implications in the treatment approach of other diseases amenable to microbiome manipulation.JOURNAL/cltg/04.03/01720094-202305000-00002/2FFU1/v/2023-05-23T220055Z/r/image-tiff.

Effects of Glutamine, Curcumin and Fish Bioactive Peptides Alone or in Combination on Intestinal Permeability in a Chronic-Restraint Stress Model.

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 (IL1ß, 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.

The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice.

Anorexia nervosa (AN) is an eating disorder with a high mortality. About 95% of cases are women and it has a population prevalence of about 1%, but evidence-based treatment is lacking. The pathogenesis of AN probably involves genetics and various environmental factors, and an altered gut microbiota has been observed in individuals with AN using amplicon sequencing and relatively small cohorts. Here we investigated whether a disrupted gut microbiota contributes to AN pathogenesis. Shotgun metagenomics and metabolomics were performed on faecal and serum samples, respectively, from a cohort of 77 females with AN and 70 healthy females. Multiple bacterial taxa (for example, Clostridium species) were altered in AN and correlated with estimates of eating behaviour and mental health. The gut virome was also altered in AN including a reduction in viral-bacterial interactions. Bacterial functional modules associated with the degradation of neurotransmitters were enriched in AN and various structural variants in bacteria were linked to metabolic features of AN. Serum metabolomics revealed an increase in metabolites associated with reduced food intake (for example, indole-3-propionic acid). Causal inference analyses implied that serum bacterial metabolites are potentially mediating the impact of an altered gut microbiota on AN behaviour. Further, we performed faecal microbiota transplantation from AN cases to germ-free mice under energy-restricted feeding to mirror AN eating behaviour. We found that the reduced weight gain and induced hypothalamic and adipose tissue gene expression were related to aberrant energy metabolism and eating behaviour. Our 'omics' and mechanistic studies imply that a disruptive gut microbiome may contribute to AN pathogenesis.

Mental health and health behaviours among patients with eating disorders: a case-control study in France.

BACKGROUND: Eating disorders (ED) are a public health concern due to their increasing prevalence and severe associated comorbidities. The aim of this study was to identify mental health and health behaviours associated with each form of EDs. METHODS: A case-control study was performed: cases were patients with EDs managed for the first time in a specialized nutrition department and controls without EDs were matched on age and gender with cases. Participants of this study filled self-administered paper questionnaire (EDs group) or online questionnaire (non-ED group). Collected data explored socio-demographics, mental health including anxiety and depression, body image, life satisfaction, substances and internet use and presence of IBS (Irritable Bowel Syndrome). RESULTS: 248 ED patients (broad categories: 66 Restrictive, 22 Bulimic and 160 Compulsive) and 208 non-ED subjects were included in this study. Mean age was 36.0 (SD 13.0) and 34.8 (SD 11.6) in ED and non-ED groups, respectively. Among patients and non-ED subjects, 86.7% and 83.6% were female, respectively. Body Shape Questionnaire mean score was between 103.8 (SD 46.1) and 125.0 (SD 36.2) for EDs and non-ED group, respectively (p < 0.0001). ED patients had a higher risk of unsatisfactory friendly life, anxiety, depression and IBS than non-ED s (all p < 0.0001) Higher risk of anxiety, depression and IBS was found for the three categories of EDs. Higher risk of smoking was associated only with restrictive ED, while or assault history and alcohol abuse problems were associated only with bulimic ED. The risk of binge drinking was lower in all EDs categories than in non-ED. CONCLUSION: This study highlights the common comorbidities shared by all EDs patients and also identifies some specific features related to ED categories. These results should contribute to the conception of future screening and prevention programs in at risk young population as well as holistic care pathways for ED patients. This case-control study evaluated mental health and health behaviours associated with the main categories of Eating Disorders (EDs). Cases were patients with EDs initiating care in a specialized nutrition department and controls without ED were matched on age and gender with cases. Self-administered paper questionnaires were filled by ED 248 patients (66 Restrictive, 22 Bulimic and 160 Compulsive) and online questionnaire by 241 non-ED controls. Body image satisfaction was significantly worse in ED patients than in controls. (p < 0.0001). Dissatisfactory life, anxiety, depression and irritable bowel syndrome were more found in patients with all EDs categories than in non-ED (p < 0.0001). Smoking risk was increased only in restrictive patients while and assault history and alcohol abuse was increased only in bulimic patients. These results highlight the global burden of ED and related comorbidities and provide useful information for future screening, prevention and care programs.

Effect of the COVID-19 Pandemic on Healthy Components of Diet and Factors Associated with Unfavorable Changes among University Students in France.

INTRODUCTION: The COVID-19 pandemic and the lockdowns have affected many aspects of university students' daily lives, including their dietary habits. This study aimed to evaluate the change of diet quality of university students before and during the COVID-19 period, and the factors associated with unfavorable changes in diet quality. METHODS: An online cross-sectional study was performed in May 2021 among Rouen (France) university students. Socio-demographic characteristics, body mass index, depression, academic stress, risk of eating disorders and food security were collected. The French "Programme National Nutrition Santé-Guidelines Score 2" (PNNS-GS2) was used to access diet quality. RESULTS: A total of 3508 students were included, 74.4% were female, the mean age was 20.7 (SD = 2.3), and 7.0% were in a situation of food insecurity. The PNNS-GS2 score decreased between the pre- and the COVID-19 pandemic period for 33.1% of university students. The associated factors with the decrease in the PNNS-GS2 score were food insecurity, financial insecurity, not living with parents, depression, academic stress, eating disorders, being in the two first years of study and having been infected by COVID-19. CONCLUSIONS: Diets with healthy components decreased for one-third of university students since the COVID-19 pandemic, and this was shown to be associated with food insecurity, poor mental health and eating disorder. This study provides important information to help public health authorities and universities give better support to student health feeding programs during pandemics and lockdowns.

Intestinal Epithelial Toll-like Receptor 4 Deficiency Modifies the Response to the Activity-Based Anorexia Model in a Sex-Dependent Manner: A Preliminary Study.

The role of microbiota in eating disorders has recently emerged. Previous data reported that lipopolysaccharides induce anorexia and a decrease of body weight through the activation of toll-like receptor 4 (TLR4). In the activity-based anorexia (ABA) mouse model, an increase of TLR4 expression in intestinal epithelial cells (IEC) has been described. We thus aimed to characterize the role of TLR4 in IEC in the ABA model in male and female mice. For this purpose, Vill-CreERT2-TLR4 LoxP, which are depleted for TLR4 in IEC in response to 4-OH tamoxifen, were submitted (ABA) or not (CT) to the ABA procedure that combined free access to a running wheel and progressive time-limited access to food. We thus compared CT and ABA TLR4IEC-/- mice to CT and ABA TLR4IEC+/+ mice. In response to the ABA model, TLR4IEC+/+ male and female mice exhibited a body weight loss associated to a decrease of lean mass. In TLR4IEC-/- male mice, body weight loss was delayed and less pronounced compared to TLR4IEC+/+ male mice. We did not observe a difference of body weight loss in female mice. The body composition remained unchanged between TLR4IEC-/- and TLR4IEC+/+ mice in both sexes. In both sexes, ABA TLR4IEC+/+ mice exhibited an increase of food-anticipatory activity, as well as an increase of immobility time during the open field test. However, female TLR4IEC-/- mice showed a decrease of the time spent at the centre and an increase of the time spent at the periphery of the open field area, whereas we did not observe differences in the male mice. In conclusion, the invalidation of TLR4 in IEC modified the response to the ABA model in a sex-dependent manner. Further studies should decipher the underlying mechanisms.

Evaluation of a Supervised Adapted Physical Activity Program Associated or Not with Oral Supplementation with Arginine and Leucine in Subjects with Obesity and Metabolic Syndrome: A Randomized Controlled Trial.

Background: In patients with obesity and metabolic syndrome (MetS), lifestyle interventions combining diet, in particular, and physical exercise are recommended as the first line treatment. Previous studies have suggested that leucine or arginine supplementation may have beneficial effects on the body composition or insulin sensitivity and endothelial function, respectively. We thus conducted a randomized controlled study to evaluate the effects of a supervised adapted physical activity program associated or not with oral supplementation with leucine and arginine in MetS-complicated patients with obesity. Methods: Seventy-nine patients with obesity and MetS were randomized in four groups: patients receiving arginine and leucine supplementation (ALs group, n = 20), patients on a supervised adapted physical activity program (APA group, n = 20), patients combining ALs and APA (ALs+APA group, n = 20), and a control group (n = 19). After the baseline evaluation (m0), patients received ALs and/or followed the APA program for 6 months (m6). Body composition, MetS parameters, lipid and glucose metabolism markers, inflammatory markers, and a cardiopulmonary exercise test (CPET) were assessed at m0, m6, and after a 3-month wash-out period (m9). Results: After 6 months of intervention, we did not observe variable changes in body weight, body composition, lipid and glucose metabolism markers, inflammatory parameters, or quality of life scores between the four groups. However, during the CPET, the maximal power (Pmax and Ppeak), power, and O2 consumption at the ventilatory threshold (P(VT) and O2(VT)) were improved in the APA and ALs+APA groups (p < 0.05), as well as the forced vital capacity (FVC). Between m6 and m9, a gain in fat mass was only observed in patients in the APA and ALs+APA groups. Conclusion: In our randomized controlled trial, arginine and leucine supplementation failed to improve MetS in patients with obesity, as did the supervised adapted physical activity program and the combination of both. Only the cardiorespiratory parameters were improved by exercise training.

Fatty acids produced by the gut microbiota dampen host inflammatory responses by modulating intestinal SUMOylation.

The gut microbiota produces a wide variety of metabolites, which interact with intestinal cells and contribute to host physiology. The effect of gut commensal bacteria on host protein SUMOylation, an essential ubiquitin-like modification involved in various intestinal functions, remains, however, unknown. Here, we show that short chain fatty acids (SCFAs) and branched chain fatty acids (BCFAs) produced by the gut microbiota increase protein SUMOylation in intestinal cells in a pH-dependent manner. We demonstrate that these metabolites inactivate intestinal deSUMOylases and promote the hyperSUMOylation of nuclear matrix-associated proteins. We further show that BCFAs inhibit the NF-κB pathway, decrease pro-inflammatory cytokine expression, and promote intestinal epithelial integrity. Together, our results reveal that fatty acids produced by gut commensal bacteria regulate intestinal physiology by modulating SUMOylation and illustrate a new mechanism of dampening of host inflammatory responses triggered by the gut microbiota.

Accuracy of bioimpedance equations for measuring body composition in a cohort of 2134 patients with obesity.

INTRODUCTION: Measuring body composition is an important issue to phenotype patients with obesity and to follow the nutritional care efficiency. Bioelectrical Impedance Analysis (BIA) is a simple and rapid technique. However, validity of BIA in patients with obesity remains controversial. Thus, we aimed to evaluate the validity of several BIA equations to assess body composition in a large cohort of patients with obesity by using dual X ray absorptiometry (DXA) as reference. METHODS: Seven BIA equations have been retrospectively applied on electrical data measured by BIA in patients with obesity with BMI equal or higher than 30 kg/m2 and results were compared to DXA-derived fat mass (FM) and fat-free mass (FFM). BIA and DXA were done the same day after an overnight fasting. Results were compared with Bland-Altman method and Pearson correlation. We also calculated the accuracy defined as the percentage of patients with DXA-BIA difference within ± 10% of DXA measures for FFM and FM. RESULTS: Data from 2134 patients with class I and II obesity (ob1/2, n = 1452, 47.4 ± 14.2 y; 35.0 ± 2.7 kg.m-2) and class III obesity (ob3, n = 682, 48.2 ± 13.9 y; 44.1 ± 3.5 kg.m-2) were analyzed. The best results to evaluate FFM both in ob1/2 and ob3 groups were obtained with Roubenoff's equation: Bland Altman bias at -1.96 and -0.82 kg, Pearson correlation r at 0.93 and 0.87, accuracy at 75.7% and 83.3%, respectively. However, limits of agreements at 95% were high: [-9.42; 5.49 kg] and [-8.16; 6.52 kg]. For FM evaluation, Roubenoff's equation also showed best results for ob1/2 group (bias at -1.17 kg; correlation r at 0.89 and accuracy at 79.1%) but not for ob3 group. In this latter group, Deurenberg's equation exhibited the best results (bias at 2.09 kg; correlation r at 0.81 and accuracy at 76.8%). However, limits of agreements remained high. CONCLUSION: In patients with obesity, Roubenoff BIA equation should be recommended to assess fat free mass, even if limits of agreements remain high.

Intestinal permeability and appetite regulating peptides-reactive immunoglobulins in severely malnourished women with anorexia nervosa.

BACKGROUND & AIMS: In the last decades, the role of microbiota-gut-brain axis has emerged in the regulation of eating behavior and in the pathophysiology of anorexia nervosa (AN) that remains poorly understood. Particularly, a gut-derived dysregulation of immune response has been proposed leading to immunoglobulins directed against appetite-regulating peptides. However, intestinal permeability in patients with anorexia nervosa has been poorly documented. METHODS: In the present prospective case-control study, we thus compared intestinal permeability, appetite-regulating peptides and their reactive immunoglobulins measured in severely malnourished women with AN (n = 17; 28 [21-35] y; 14.9 [14.1-15.2] kg/m2) to healthy volunteers (HV, n = 34; 26 [23-35] y; 22.3 [20.6-23.6] kg/m2). RESULTS: Patients with AN exhibited an increased urinary lactulose/mannitol ratio, both in 0-5 h (0.033 [0.013-0.116]) and 5-24 h samples (0.115 [0.029-0.582]), when compared to HV (0.02 [0.008-0.045], p = 0.0074 and 0.083 [0.019-0.290], p = 0.0174, respectively), suggesting an increased intestinal permeability. Urinary excretion of sucralose and plasma zonulin were not different. The levels of plasma total ghrelin and desacyl-ghrelin were increased in patients with AN compared to HV, whereas plasma leptin concentration was decreased. In addition, αMSH remained unchanged compared to HV. Finally, we did not observe any modification of the levels of total or free αMSH, leptin or ghrelin-reactive immunoglobulin G and M, as well as for their affinity properties. Only, a weak decrease of the dissociation constant (kd) for acyl-ghrelin-reactive IgG was observed in patients with AN (p = 0.0411). CONCLUSIONS: In conclusion, severely malnourished patients with AN show a higher intestinal permeability than HV without evidence of an effect on appetite regulating peptides-reactive immunoglobulins.

Dysbiotic Gut Bacteria in Obesity: An Overview of the Metabolic Mechanisms and Therapeutic Perspectives of Next-Generation Probiotics.

Obesity, a worldwide health concern with a constantly rising prevalence, is a multifactorial chronic disease associated with a wide range of physiological disruptions, including energy imbalance, central appetite and food reward dysregulation, and hormonal alterations and gut dysbiosis. The gut microbiome is a well-recognized factor in the pathophysiology of obesity, and its influence on host physiology has been extensively investigated over the last decade. This review highlights the mechanisms by which gut dysbiosis can contribute to the pathophysiology of obesity. In particular, we discuss gut microbiota's contribution to host energy homeostatic changes, low-grade inflammation, and regulation of fat deposition and bile acid metabolism via bacterial metabolites, such as short-chain fatty acids, and bacterial components, such as lipopolysaccharides, among others. Finally, therapeutic strategies based on next-generation probiotics aiming to re-shape the intestinal microbiota and reverse metabolic alterations associated with obesity are described.

Delayed avoidant restrictive food intake disorder diagnosis leading to Ogilvie's syndrome in an adolescent.

PURPOSE: Avoidant restrictive food intake disorder (ARFID) was recently characterized, according to the DSM-5 classification, as a feeding and eating disorder (FED). However, ARFID remains poorly known by most pediatricians, but also by psychiatrists and primary care professionals. Despite the fact that patients with ARFID generally have a higher BMI than patients with anorexia nervosa, our purpose was to highlight the fact that they may present severe nutritional deficiencies and major somatic complications when the diagnosis is delayed. METHOD: We describe here a case of a 16-year-old boy who presented with severe undernutrition (BMI = 11.5) leading to Ogilvie's syndrome, which resolved with enteral refeeding. Because of undernutrition, very bad dental condition, and encopresis, some physicians wrongly suspected child neglect, but retrospective analysis of his personal history revealed a long-term FED and sensory specificities that led to the final diagnosis of an ARFID-autism spectrum disorder (ASD) association. A literature review was conducted on the ARFID somatic complications. CONCLUSION: The training of health professionals in the clinical forms of pediatric FED, including ARFID, is necessary, to promote early diagnosis and prevent poor nutritional outcomes. In this case the association of ARFID-ASD and the delay in access to specialized care favored by the disadvantaged social environment led to severe gastrointestinal complications. LEVEL OF EVIDENCE: V, descriptive study.

Eater profile and associated factors in pediatric patients of the PEDIANUT cohort.

Appetite traits have multifactorial origins. In association with environmental and genetic factors, they could become problematic and lead to Feeding or Eating Disorders (FED). As the DSM-5 classification is not suitable for pediatric FED, another way to describe eating behavior is to distinguish the clinical profiles of "small eater" and "big eater". The aim of this study was to identify socio-demographic and medical factors associated with these profiles, and to compare problematic and non-problematic profiles. From the Pedianut study, we analyzed socio-demographic, medical and family history data among 401 children according to 4 age groups (<1 year n = 101, 1-6 years n = 99, 6-12 years n = 100, 12-18 years n = 101). The information collected on eating behavior made it possible to define small eater profile (SEP) and big eater profile (BEP) using predefined grids. BEP was more frequent in adolescents (35.6%), and SEP was more frequent in children aged 1-6 years (34.3%). BEP was associated with having separated parents, being male and the oldest sibling (p < 0.05). Problematic BEP was associated with eating while watching television, being a girl, and having sensory disorders (p < 0.05). SEP was associated, whatever age, with non-breastfeeding, chronic illness, psychological history, sensory disorders, language delays (in the 1-6 year age group), and family history of FED (in the adolescent group) (p < 0.05). This analysis of factors associated with eater profile opens new perspectives for research on risk factors associated with eating traits, which warrants further study in larger populations to delineate transition from healthy to problematic eating.

Role of microbiota-gut-brain axis dysfunctions induced by infections in the onset of anorexia nervosa.

Anorexia nervosa (AN) is an eating disorder characterized by low food intake, severe body weight loss, intense fear of gaining weight, and dysmorphophobia. This chronic disease is associated with both psychiatric and somatic comorbidities. Over the years, clinical studies have accumulated evidence that viral or bacterial infections may promote the onset of eating disorders such as AN. This review aims to describe how infections and the subsequent immune responses affect food intake regulation in the short term and also how these processes may lead to long-term intestinal disorders, including gut barrier disruption and gut microbiota dysbiosis, even after the clearance of the pathogens. We discuss in particular how infection-mediated intestinal dysbiosis may promote the onset of several AN symptoms and comorbidities, including appetite dysregulation, functional gastrointestinal disorders, and mood disorders.