Abbreviations: ALT, alanine aminotransferase; C/EBPα, CCAAT/enhancer binding protein alpha; CHOP, CCAAT-enhancer-binding protein homologous protein; CYP2E1, cytochrome P450 2E1; DAMPs, danger-associated molecular patterns; FABP1, fatty acid binding protein 1; FAS, fatty acid synthase; FAT/CD36, fatty acid translocase CD36; FFA, free fatty acid; FOXA1, forkhead box protein A1; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GRP78, 78 kDa glucose-regulated protein; HFD, high fat diet; HOMA-IR, homeostasis model assessment of insulin resistance; IAP, intestinal phosphatase alkaline; IL-6, interleukin 6; LPO, lipid peroxidation; LPS, lipopolysaccharide; LXRα, liver X receptor alpha; NAFLD, non-alcoholic fatty liver disease; NAS, NAFLD activity score; NASH, non-alcoholic steatohepatitis; NF-B , nuclear factor kappa B; NLRP3, NOD-like receptor family pyrin domain containing 3;PAMPs, pathogen-associated molecular patterns; PRRs, pattern recognition receptors; SCFAs, short-chain fatty acids; SREBP-1c, sterol regulatory element binding protein 1c; TG, triglycerides; TLR, Toll-like receptor; TNF-αtumor necrosis factor; UPR, unfolded protein response. AbstractGut microbiota is involved in obesity, metabolic syndrome and the progression of nonalcoholic fatty liver disease (NAFLD). It has been recently suggested that the flavonoid quercetin may have the ability to modulate the intestinal microbiota composition, suggesting a prebiotic capacity which highlights a great therapeutic potential in NAFLD. The present study aims to investigate benefits of experimental treatment with quercetin on gut microbial balance and related gut-liver axis activation in a nutritional animal model of NAFLD associated to obesity. C57BL/6J mice were challenged with high fat diet (HFD) supplemented or not with quercetin for 16 weeks.

Childhood obesity has reached epidemic levels, representing one of the most serious public health concerns associated with metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). There is limited clinical experience concerning pediatric NAFLD patients, and thus the therapeutic options are scarce. The aim of this study was to evaluate the benefits of exercise on gut microbiota composition and functionality balance, and consequent effects on early obesity and NAFLD onset in an in vivo model. Juvenile (21-day-old) male Wistar rats fed a control diet or a high-fat diet (HFD) were subjected to a combined aerobic and resistance training protocol. Fecal microbiota was sequenced by an Illumina MiSeq system, and parameters related to metabolic syndrome, fecal metabolome, intestinal barrier integrity, bile acid metabolism and transport, and alteration of the gut-liver axis were measured. Exercise decreased HFD-induced body weight gain, metabolic syndrome and hepatic steatosis, as a result of its lipid metabolism modulatory capacity. Gut microbiota composition and functionality were substantially modified as a consequence of diet, age and exercise intervention. In addition, the training protocol increased Parabacteroides , Bacteroides and Flavobacterium genera, correlating with a beneficial metabolomic profile, whereas Blautia , Dysgonomonas and Porphyromonas showed an opposite pattern. Exercise effectively counteracted HFD-induced microbial imbalance, leading to intestinal barrier preservation, which, in turn, prevented deregulation of the gut-liver axis and improved bile acid homeostasis, determining the clinical outcomes of NAFLD. In conclusion, we provide scientific evidence highlighting the benefits of gut microbiota composition and functionality modulation by physical exercise protocols in the management of early obesity and NAFLD development.

Childhood obesity has reached epidemic levels and is a serious health concern associated with metabolic syndrome, nonalcoholic fatty liver disease, and gut microbiota alterations. Physical exercise is known to counteract obesity progression and modulate the gut microbiota composition. This study aims to determine the effect of a 12-week strength and endurance combined training program on gut microbiota and inflammation in obese pediatric patients. Thirty-nine obese children were assigned randomly to the control or training group. Anthropometric and biochemical parameters, muscular strength, and inflammatory signaling pathways in mononuclear cells were evaluated. Bacterial composition and functionality were determined by massive sequencing and metabolomic analysis. Exercise reduced plasma glucose levels and increased dynamic strength in the upper and lower extremities compared with the obese control group. Metagenomic analysis revealed a bacterial composition associated with obesity, showing changes at the phylum, class, and genus levels. Exercise counteracted this profile, significantly reducing the Proteobacteria phylum and Gammaproteobacteria class. Moreover, physical activity tended to increase some genera, such as Blautia, Dialister, and Roseburia, leading to a microbiota profile similar to that of healthy children. Metabolomic analysis revealed changes in short-chain fatty acids, branched-chain amino acids, and several sugars in response to exercise, in correlation with a specific microbiota profile. Finally, the training protocol significantly inhibited the activation of the obesity-associated NLRP3 signaling pathway. Our data suggest the existence of an obesity-related deleterious microbiota profile that is positively modified by physical activity intervention. Exercise training could be considered an efficient nonpharmacological therapy, reducing inflammatory signaling pathways induced by obesity in children via microbiota modulation.

BackgroundPersonality influences an individual’s adaptation to a specific job or organization. Little is known about personality trait differences between medical career and specialty choices after graduating from medical school when actually practicing different medical specialties. Moreover, whether personality traits contribute to important career choices such as choosing to work in the private or public sector or with clinical patient contact, as well as change of specialty, have remained largely unexplored. In a nationally representative sample of Finnish physicians (N = 2837) we examined how personality traits are associated with medical career choices after graduating from medical school, in terms of employment sector, patient contact, medical specialty and change of specialty.MethodsPersonality was assessed using the shortened version of the Big Five Inventory (S-BFI). An analysis of covariance with posthoc tests for pairwise comparisons was conducted, adjusted for gender and age with confounders (employment sector, clinical patient contact and medical specialty).ResultsHigher openness was associated with working in the private sector, specializing in psychiatry, changing specialty and not practicing with patients. Lower openness was associated with a high amount of patient contact and specializing in general practice as well as ophthalmology and otorhinolaryngology. Higher conscientiousness was associated with a high amount of patient contact and specializing in surgery and other internal medicine specialties. Lower conscientiousness was associated with specializing in psychiatry and hospital service specialties. Higher agreeableness was associated with working in the private sector and specializing in general practice and occupational health. Lower agreeableness and neuroticism were associated with specializing in surgery. Higher extraversion was associated with specializing in pediatrics and change of specialty. Lower extraversion was associated with not practicing with patients.ConclusionsThe results showed distinctive personality traits to be associated with physicians’ career and specialty choices after medical school independent of known confounding factors. Openness was the most consistent personality trait associated with physicians’ career choices in terms of employment sector, amount of clinical patient contact, specialty choice and change of specialty. Personality-conscious medical career counseling and career guidance during and after medical education might enhance the person-job fit among physicians.

Obesity and associated comorbidities, including non-alcoholic fatty liver disease (NAFLD), are a major concern to public well-being worldwide due to their high prevalence among the population, and its tendency on the rise point to as important threats in the future. Therapeutic approaches for obesity-associated disorders have been circumscribed to lifestyle modifications and pharmacological therapies have demonstrated limited efficacy. Over the last few years, different studies have shown a significant role of intestinal microbiota (IM) on obesity establishment and NAFLD development. Therefore, modulation of IM emerges as a promising therapeutic strategy for obesity-associated diseases. Administration of prebiotic and probiotic compounds, fecal microbiota transplantation (FMT) and exercise protocols have shown a modulatory action over the IM. In this review we provide an overview of current approaches targeting IM which have shown their capacity to counteract NAFLD and metabolic syndrome features in human patients and animal models.