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Cell Host & Microbe Dec 2023Exclusive enteral nutrition (EEN) with fiber-free diets is an effective steroid-sparing treatment to induce clinical remission in children with Crohn's disease (CD)....
Exclusive enteral nutrition (EEN) with fiber-free diets is an effective steroid-sparing treatment to induce clinical remission in children with Crohn's disease (CD). However, the mechanism underlying the beneficial effects of EEN remains obscure. Using a model of microbiota-dependent colitis with the hallmarks of CD, we find that the administration of a fiber-free diet prevents the development of colitis and inhibits intestinal inflammation in colitic animals. Remarkably, fiber-free diet alters the intestinal localization of Mucispirillum schaedleri, a mucus-dwelling pathobiont, which is required for triggering disease. Mechanistically, the absence of dietary fiber reduces nutrient availability and impairs the dissimilatory nitrate reduction to ammonia (DNRA) metabolic pathway of Mucispirillum, leading to its exclusion from the mucus layer and disease remission. Thus, appropriate localization of the specific pathobiont in the mucus layer is critical for disease development, which is disrupted by fiber exclusion. These results suggest strategies to treat CD by targeting the intestinal niche and metabolism of disease-causing microbes.
Topics: Humans; Child; Animals; Crohn Disease; Diet; Colitis; Treatment Outcome; Microbiota
PubMed: 37967555
DOI: 10.1016/j.chom.2023.10.016 -
Nutrition, Metabolism, and... Aug 2023To assess whether intermittent fasting (IF) diets are associated with improvement in weight loss, metabolic parameters, and subjective well-being, in people with obesity. (Meta-Analysis)
Meta-Analysis
AIM
To assess whether intermittent fasting (IF) diets are associated with improvement in weight loss, metabolic parameters, and subjective well-being, in people with obesity.
DATA SYNTHESIS
We performed a Meta-analysis of Randomized Controlled Trials longer than 2 months, retrieved through an extensive search on MedLine, Cochrane CENTRAL Library, and Embase online databases, comparing weight loss with IF diets and control diets in people with Body Mass index (BMI) > 30 kg/m. We retrieved 9 trials, enrolling 540 patients. IF was not associated with a significantly greater reduction of body weight or BMI at any time point with respect to controls or in respect to continuous restricted diets, with low-to moderate quality of evidence; no significant difference in efficacy between alternate day fasting and time restricted eating was found. Differences in fasting plasma glucose, total or high-density lipoprotein cholesterol or blood pressure at any time point were not statistically significant, whereas a reduction of low-density lipoprotein cholesterol (MD -8.39 [-15.96, -0.81] mg/dl, P = 0.03; I = 0%) was observed at 2-4 months, but not in the longer term. Data on psychological parameters and overall well-being were insufficient to perform a formal meta-analysis, whereas a qualitative synthesis did not show any difference between IF and controls.
CONCLUSIONS
IF is not associated with greater or lesser weight loss than non-intermittent fasting diets. Further data on psychological parameters and overall well-being are needed to properly assess the role of IF diets in the management of obesity.
Topics: Humans; Randomized Controlled Trials as Topic; Obesity; Weight Loss; Fasting; Cholesterol, HDL
PubMed: 37248144
DOI: 10.1016/j.numecd.2023.05.005 -
Nature Microbiology Feb 2024A strong correlation between gut microbes and host health has been observed in numerous gut metagenomic cohort studies. However, the underlying mechanisms governing...
A strong correlation between gut microbes and host health has been observed in numerous gut metagenomic cohort studies. However, the underlying mechanisms governing host-microbe interactions in the gut remain largely unknown. Here we report that the gut commensal Christensenella minuta modulates host metabolism by generating a previously undescribed class of secondary bile acids with 3-O-acylation substitution that inhibit the intestinal farnesoid X receptor. Administration of C. minuta alleviated features of metabolic disease in high fat diet-induced obese mice associated with a significant increase in these acylated bile acids, which we refer to as 3-O-acyl-cholic acids. Specific knockout of intestinal farnesoid X receptor in mice counteracted the beneficial effects observed in their wild-type counterparts. Finally, we showed that 3-O-acyl-CAs were prevalent in healthy humans but significantly depleted in patients with type 2 diabetes. Our findings indicate a role for C. minuta and acylated bile acids in metabolic diseases.
Topics: Humans; Animals; Mice; Bile Acids and Salts; Diabetes Mellitus, Type 2; Clostridiales; Diet, High-Fat
PubMed: 38233647
DOI: 10.1038/s41564-023-01570-0 -
Microbiome Nov 2023Diet-induced dyslipidemia is linked to the gut microbiota, but the causality of microbiota-host interaction affecting lipid metabolism remains controversial. Here, the...
BACKGROUND
Diet-induced dyslipidemia is linked to the gut microbiota, but the causality of microbiota-host interaction affecting lipid metabolism remains controversial. Here, the humanized dyslipidemia mice model was successfully built by using fecal microbiota transplantation from dyslipidemic donors (FMT-dd) to study the causal role of gut microbiota in diet-induced dyslipidemia.
RESULTS
We demonstrated that FMT-dd reshaped the gut microbiota of mice by increasing Faecalibaculum and Ruminococcaceae UCG-010, which then elevated serum cholicacid (CA), chenodeoxycholic acid (CDCA), and deoxycholic acid (DCA), reduced bile acid synthesis and increased cholesterol accumulation via the hepatic farnesoid X receptor-small heterodimer partner (FXR-SHP) axis. Nevertheless, high-fat diet led to decreased Muribaculum in the humanized dyslipidemia mice induced by FMT-dd, which resulted in reduced intestinal hyodeoxycholic acid (HDCA), raised bile acid synthesis and increased lipid absorption via the intestinal farnesoid X receptor-fibroblast growth factor 19 (FXR-FGF19) axis.
CONCLUSIONS
Our studies implicated that intestinal FXR is responsible for the regulation of lipid metabolism in diet-induced dyslipidemia mediated by gut microbiota-bile acid crosstalk. Video Abstract.
Topics: Animals; Mice; Bile Acids and Salts; Diet, High-Fat; Gastrointestinal Microbiome; Lipid Metabolism; Liver; Mice, Inbred C57BL
PubMed: 38001551
DOI: 10.1186/s40168-023-01709-5 -
The American Journal of Clinical... Mar 2024Weight loss is the most effective treatment for nonalcoholic fatty liver disease (NAFLD). There is evidence that the Mediterranean diets rich in unsaturated fatty acids... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Weight loss is the most effective treatment for nonalcoholic fatty liver disease (NAFLD). There is evidence that the Mediterranean diets rich in unsaturated fatty acids and fiber have beneficial effects on weight homeostasis and metabolic risk factors in individuals with NAFLD. Studies have also shown that higher circulating concentrations of pentadecanoic acid (C15:0) are associated with a lower risk for NAFLD.
OBJECTIVES
To examine the effects of a Mediterranean-like, culturally contextualized Asian diet rich in fiber and unsaturated fatty acids, with or without C15:0 supplementation, in Chinese females with NAFLD.
METHODS
In a double-blinded, parallel-design, randomized controlled trial, 88 Chinese females with NAFLD were randomly assigned to 1 of the 3 groups for 12 wk: diet with C15:0 supplementation (n = 31), diet without C15:0 supplementation (n = 28), or control (habitual diet and no C15:0 supplementation, n = 29). At baseline and after the intervention, body fat percentage, intrahepatic lipid content, muscle and abdominal fat, liver enzymes, cardiometabolic risk factors, and gut microbiome were assessed.
RESULTS
In the intention-to-treat analysis, weight reductions of 4.0 ± 0.5 kg (5.3%), 3.4 ± 0.5 kg (4.5%), and 1.5 ± 0.5 kg (2.1%) were achieved in the diet-with-C15:0, diet without-C15:0, and the control groups, respectively. The proton density fat fraction (PDFF) of the liver decreased by 33%, 30%, and 10%, respectively. Both diet groups achieved significantly greater reductions in body weight, liver PDFF, total cholesterol, gamma-glutamyl transferase, and triglyceride concentrations compared with the control group. C15:0 supplementation reduced LDL-cholesterol further, and increased the abundance of Bifidobacterium adolescentis. Fat mass, visceral adipose tissue, subcutaneous abdominal adipose tissue (deep and superficial), insulin, glycated hemoglobin, and blood pressure decreased significantly in all groups, in parallel with weight loss.
CONCLUSION
Mild weight loss induced by a Mediterranean-like diet adapted for Asians has multiple beneficial health effects in females with NAFLD. C15:0 supplementation lowers LDL-cholesterol and may cause beneficial shifts in the gut microbiome.
TRIAL REGISTRATION NUMBER
This trial was registered at the clinicaltrials.gov as NCT05259475.
Topics: Female; Humans; Non-alcoholic Fatty Liver Disease; Diet, Mediterranean; Liver; Weight Loss; Fatty Acids, Unsaturated; Cholesterol; Fatty Acids
PubMed: 38035997
DOI: 10.1016/j.ajcnut.2023.11.013 -
Microbial Biotechnology Oct 2023It has been reported that Akkermansia muciniphila improves host metabolism and reduces inflammation; however, its potential effects on bile acid metabolism and metabolic...
It has been reported that Akkermansia muciniphila improves host metabolism and reduces inflammation; however, its potential effects on bile acid metabolism and metabolic patterns in metabolic-associated fatty liver disease (MAFLD) are unknown. In this study, we have analysed C57BL/6 mice under three feeding conditions: (i) a low-fat diet group (LP), (ii) a high-fat diet group (HP) and (iii) a high-fat diet group supplemented with A. muciniphila (HA). The results found that A. muciniphila administration relieved weight gain, hepatic steatosis and liver injury induced by the high-fat diet. A. muciniphila altered the gut microbiota with a decrease in Alistipes, Lactobacilli, Tyzzerella, Butyricimonas and Blautia, and an enrichment of Ruminiclostridium, Osclibacter, Allobaculum, Anaeroplasma and Rikenella. The gut microbiota changes correlated significantly with bile acids. Meanwhile, A. muciniphila also improved glucose tolerance, gut barriers and adipokines dysbiosis. Akkermansia muciniphila regulated the intestinal FXR-FGF15 axis and reshaped the construction of bile acids, with reduced secondary bile acids in the caecum and liver, including DCA and LCA. These findings provide new insights into the relationships between probiotics, microflora and metabolic disorders, highlighting the potential role of A. muciniphila in the management of MAFLD.
Topics: Animals; Mice; Diet, High-Fat; Gastrointestinal Microbiome; Bile Acids and Salts; Mice, Inbred C57BL; Verrucomicrobia; Metabolic Diseases; Liver Diseases
PubMed: 37377410
DOI: 10.1111/1751-7915.14293 -
Obesity (Silver Spring, Md.) Sep 2023The aim of this study was to investigate the effectiveness of an intermittent low-carbohydrate diet (ILCD) versus calorie restriction (ICR) in young populations and... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The aim of this study was to investigate the effectiveness of an intermittent low-carbohydrate diet (ILCD) versus calorie restriction (ICR) in young populations and potential mechanisms.
METHODS
Thirty-four participants aged 9 to 30 years with cardiometabolic risk were randomized to receive a self-administered 2-week ILCD (carbohydrate intake ≤ 50 g/d on seven nonconsecutive days) or ICR (500-600 kcal/d for two consecutive days per week). Differences in changes in obesity measures, glycemic and lipid profiles, gut microbiota composition, and three serum biomarkers were compared.
RESULTS
The ILCD and ICR similarly reduced body weight, waist circumference, fasting glucose, insulin, postprandial glucose variation, monocyte chemoattractant protein-1, free fatty acid, and fibroblast growth factor 21, whereas ILCD produced significantly different alterations in the following outcomes compared with ICR: greater increases in low-density lipoprotein cholesterol and total cholesterol (-0.36 mmol/L, 95% CI: -0.68 to -0.04; -0.40 mmol/L, 95% CI: -0.73 to -0.06) and greater decrease in triglyceride (0.20 mmol/L, 95% CI: 0.04 to 0.37). Actinobacteria and Bifidobacterium reduced after ILCD but not ICR; and the reductions strongly correlated with changes in fasting glucose (both r = 0.84) and low-density lipoprotein cholesterol (r = -0.81 and -0.72).
CONCLUSIONS
This study found no evidence of differences in changes from baseline in obesity measures, glucose regulation, and inflammation between ILCD and ICR, despite trends in reduction in those parameters. However, there seemed to be some differences in responses in lipids and gut microbiota.
Topics: Humans; Caloric Restriction; Dietary Carbohydrates; Obesity; Cholesterol, LDL; Cardiovascular Diseases; Glucose; Blood Glucose
PubMed: 37545298
DOI: 10.1002/oby.23855 -
Nutrients Oct 2023Melanoma, a prevalent and lethal form of skin cancer, remains a formidable challenge in terms of prevention and treatment. While significant progress has been made in... (Review)
Review
Melanoma, a prevalent and lethal form of skin cancer, remains a formidable challenge in terms of prevention and treatment. While significant progress has been made in understanding its pathogenesis and treatment, the quest for effective prevention strategies and therapeutic approaches remains ongoing. Considering the increased advancements in understanding the dynamic interplay between nutrients and melanoma, we aim to offer a refreshed perspective on nutrient-based approaches for melanoma prevention and adjunctive therapy. In contrast to other studies, we have innovatively provided a detailed exposition of the nutrients' influences on melanoma prognosis and treatment. This review firstly examines various nutrients, including antioxidants (namely vitamins A, D, C, and E; selenium; and caffeine), polyunsaturated fatty acids, and flavonoids, for their effects and underlying mechanisms in reducing melanoma risk. Among these nutrients, caffeine shows the most promising potential, as it is supported by multiple cohort studies for its protective effect against melanoma. In contrast, there is a certain degree of inconsistency in the research of other nutrients, possibly due to inherent differences between animal studies and epidemiological research, as well as variations in the definition of nutrient intake. To comprehensively investigate the impact of nutrients on melanoma progression and therapeutic approaches, the following sections will explore how nutrients influence immune responses and other physiological processes. While there is robust support from cell and animal studies regarding the immunomodulatory attributes of vitamins D and zinc, the anti-angiogenic potential of polyphenols, and the cell growth-inhibitory effects of flavonoids, the limited availability of human-based research substantially constrains their practical relevance in clinical contexts. As for utilizing nutrients in adjuvant melanoma treatments, multiple approaches have garnered clinical research support, including the utilization of vitamin D to decrease the postoperative recurrence rates among melanoma patients and the adoption of a high-fiber diet to enhance the effectiveness of immunotherapy. In general, the effects of most nutrients on reducing the risk of melanoma are not entirely clear. However, several nutrients, including vitamin D and dietary fiber, have demonstrated their potential to improve the melanoma prognosis and enhance the treatment outcomes, making them particularly deserving of clinical attention. A personalized and interdisciplinary approach, involving dermatologists, oncologists, nutritionists, and researchers, holds the promise of optimizing melanoma treatment strategies.
Topics: Humans; Caffeine; Vitamins; Melanoma; Vitamin D; Vitamin A; Flavonoids; Diet
PubMed: 37892558
DOI: 10.3390/nu15204483 -
The Journal of Clinical Endocrinology... Nov 2023Childhood overweight has been linked to earlier development of adrenarche and puberty, but it remains unknown if lifestyle interventions influence sexual maturation in...
CONTEXT
Childhood overweight has been linked to earlier development of adrenarche and puberty, but it remains unknown if lifestyle interventions influence sexual maturation in general populations.
OBJECTIVE
To investigate if a 2-year lifestyle intervention influences circulating androgen concentrations and sexual maturation in a general population of children.
METHODS
We conducted a 2-year physical activity and dietary intervention study in which 421 prepubertal and mostly normal-weight 6- to 9-year-old children were allocated either to a lifestyle intervention group (119 girls, 132 boys) or a control group (84 girls, 86 boys). The main outcome measures were serum dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), and testosterone concentrations, and clinical adrenarchal and pubertal signs.
RESULTS
The intervention and control groups had no differences in body size and composition, clinical signs of androgen action, and serum androgens at baseline. The intervention attenuated the increase of DHEA (P = .032), DHEAS (P = .001), A4 (P = .003), and testosterone (P = .007) and delayed pubarche (P = .038) in boys but it only attenuated the increase of DHEA (P = .013) and DHEAS (P = .003) in girls. These effects of lifestyle intervention on androgens and the development of pubarche were independent of changes in body size and composition, but the effects of intervention on androgens were partly explained by changes in fasting serum insulin.
CONCLUSION
A combined physical activity and dietary intervention attenuates the increase of serum androgen concentrations and sexual maturation in a general population of prepubertal and mostly normal-weight children, independently of changes in body size and composition.
Topics: Child; Female; Humans; Male; Adrenarche; Androgens; Androstenedione; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Puberty; Testosterone; Exercise; Diet, Healthy
PubMed: 37329220
DOI: 10.1210/clinem/dgad367 -
Clinical Nutrition (Edinburgh, Scotland) Aug 2023Diet may play an essential role in the aetiology of bladder cancer (BC). Vitamin D is involved in various biological functions which have the potential to prevent BC... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Diet may play an essential role in the aetiology of bladder cancer (BC). Vitamin D is involved in various biological functions which have the potential to prevent BC development. Besides, vitamin D also influences the uptake of calcium and phosphorus, thereby possibly indirectly influencing the risk of BC. The aim of the present study was to investigate the relation between vitamin D intake and BC risk.
METHODS
Individual dietary data were pooled from ten cohort studies. Food item intake was converted to daily intakes of vitamin D, calcium and phosphorus. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs) were obtained using Cox-regression models. Analyses were adjusted for gender, age and smoking status (Model 1), and additionally for the food groups fruit, vegetables and meat (Model 2). Dose-response relationships (Model 1) were examined using a nonparametric test for trend.
RESULTS
In total, 1994 cases and 518,002 non-cases were included in the analyses. The present study showed no significant associations between individual nutrient intake and BC risk. A significant decreased BC risk was observed for high vitamin D intake with moderate calcium and low phosphorus intake (Model 2: HR: 0.77, 95% CI: 0.59-1.00). No significant dose-response analyses were observed.
CONCLUSION
The present study showed a decreased BC risk for high dietary vitamin D intake in combination with low calcium intake and moderate phosphorus intake. The study highlights the importance of examining the effect of a nutrient in combination with complementary nutrients for risk assessment. Future research should focus on nutrients in a wider context and in nutritional patterns.
Topics: Humans; Calcium; Prospective Studies; Phosphorus, Dietary; Diet; Vitamin D; Vitamins; Calcium, Dietary; Urinary Bladder Neoplasms; Cohort Studies; Phosphorus; Risk Factors
PubMed: 37321901
DOI: 10.1016/j.clnu.2023.05.010