Characterization of the Gut Microbiota in Individuals with Overweight or Obesity during a Real-World Weight Loss Dietary Program: A Focus on the Bacteroides 2 Enterotype

Background: Dietary intervention is a cornerstone of weight loss therapies. In obesity, a dysbiotic gut microbiota (GM) is characterized by high levels of Bacteroides lineages and low diversity. We examined the GM composition changes, including the Bacteroides 2 enterotype (Bact2), in a real-world weight loss study in subjects following a high-protein hypocaloric diet with or without a live microorganisms (LMP) supplement. Method: 263 volunteers were part of this real-world weight loss program. The first phase was a high-protein low-carbohydrate calorie restriction diet with or without LMP supplements. Fecal samples were obtained at baseline and after 10% weight loss for 163 subjects. Metagenomic profiling was obtained by shotgun sequencing. Results: At baseline, the Bact2 enterotype was more prevalent in subjects with aggravated obesity and metabolic alterations. After weight loss, diversity increased and Bact2 prevalence decreased in subjects with lower GM diversity at baseline, notably in LMP consumers. Significant increases in Akkermansia muciniphila and Parabacteroides distasonis and significant decreases of Eubacterium rectale, Streptococcus thermophilus and Bifidobacterial lineages were observed after weight loss. Conclusion: Baseline microbiome composition is associated with differential changes in GM diversity and Bact2 enterotype prevalence after weight loss. Examining these signatures could drive future personalized nutrition efforts towards more favorable microbiome compositions.

Hydrogen sulfide, microbiota, and sulfur amino acid restriction diet

Eukaryotes and microbiota produce H2S, using the same substrates and enzymes which constitute the reverse-trans-sulfuration and transsulfuration pathways. The homeostasis of gut microbiota impacts on the structural and functional integrity of gut epithelial barrier. Microbiota also serve as signalling sources to inform the host of the metabolism and functional changes. Microbiota dysbiosis negatively affect human health, contributing to diseases like obesity, diabetes, inflammatory bowel diseases, and asthma. Not by coincidence, these pathological conditions are also closely related to the abnormal metabolism and function of H2S signalling.H2S serves as a bacterial signal to the host and the host-produced H2S impacts on the population and size of microbiota. These bi-directional interactions become especially important for the digestion and utilization of sulfur amino acid in diet. Dietary restriction of sulfur amino acid increases the endogenous production of H2S by the host and consequently offers many health benefits. It, on the other hand, decreases the nutritional supply to the microbiota, which could be remedied by the co-application of prebiotics and probiotics. It is strategically sound to target the expression of H2S-producing enzymes in different organs to slow aging processes in our body and promote better health.

Flexible vs. rigid dieting in resistance-trained individuals seeking to optimize their physiques: A randomized controlled trial

Background The purpose of this study was to compare a flexible vs. rigid diet on weight loss and subsequent weight regain in resistance-trained (RT) participants in a randomized, parallel group design. Methods Twenty-three males and females (25.6 ± 6.1 yrs; 170 ± 8.1 cm; 75.4 ± 10.3 kg) completed the 20-week intervention (consisting of a 10-week diet phase and a 10-week post-diet phase). Participants were randomized to a flexible diet (FLEX) comprised of non-specific foods or a rigid diet (RIGID) comprised of specific foods. Participants adhered to an ~20%kcal reduction during the first 10-weeks of the intervention and were instructed to eat ad libitum for the final 10-weeks. Body composition and resting metabolic rate were assessed 5 times: (baseline, 5, 10 [end of diet phase], 16, and 20 weeks). Results During the 10-week diet phase, both groups significantly reduced bodyweight (FLEX: baseline = 76.1 ± 8.4kg, post-diet = 73.5 ± 8.8 kg, ▲2.6 kg; RIGID: baseline = 74.9 ± 12.2 kg, post-diet = 71.9 ± 11.7 kg, ▲3.0 kg, p < 0.001); fat mass (FLEX: baseline = 14.8 ± 5.7 kg, post-diet = 12.5 ± 5.0 kg, ▲2.3 kg; RIGID: baseline = 18.1 ± 6.2 kg, post-diet = 14.9 ± 6.5 kg, ▲3.2 kg p < 0.001) and body fat% (FLEX: baseline = 19.4 ± 8.5%, post-diet = 17.0 ± 7.1%, ▲2.4%; RIGID: baseline = 24.0 ± 6.2%, post-diet = 20.7 ± 7.1%, ▲3.3%; p < 0.001). There were no significant differences between the two groups for any variable during the diet phase. During the post-diet phase, a significant diet x time interaction (p < 0.001) was observed for FFM with the FLEX group gaining a greater amount of FFM (+1.7 kg) in comparison with the RIGID group (−0.7 kg). Conclusions A flexible or rigid diet strategy is equally effective for weight loss during a caloric restriction diet in free-living, RT individuals. While post-diet FFM gains were greater in the FLEX group, there were no significant differences in the amount of time spent in resistance and aerobic exercise modes nor were there any significant differences in protein and total caloric intakes between the two diet groups. In the absence of a clear physiological rationale for increases in FFM, in addition to the lack of a standardized diet during the post-diet phase, we refrain from attributing the increases in FFM in the FLEX group to their diet assignment during the diet phase of the investigation. We recommend future research investigate additional physiological and psychological effects of flexible diets and weight regain in lean individuals.

Effects of Calorie Restriction on Health Span and Insulin Resistance: Classic Calorie Restriction Diet vs. Ketosis-Inducing Diet

As the incidence of Chronic Non-Communicable Diseases (CNCDs) increases, preventive approaches become more crucial. In this review, calorie restriction (CR) effects on human beings were evaluated, comparing the benefits and risks of different CR diets: classic CR vs. ketosis-inducing diets, including intermittent fasting (IF), classic ketogenic diet (CKD), fasting mimicking diet (FMD), very-low-calorie ketogenic Diet (VLCKD) and Spanish ketogenic Mediterranean diet (SKMD). Special emphasis on insulin resistance (IR) was placed, as it mediates metabolic syndrome (MS), a known risk factor for CNCD, and is predictive of MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.

Effects of Calorie Restriction on Health Span and Insulin Resistance: Classic Calorie Restriction Diet vs Ketosis-Inducing Diet

As Chronic Non-Communicable Diseases (CNCD) increase, preventive approaches become more crucial. In this review, Calorie Restriction (CR) effects on human beings were evaluated, comparing benefits and risks of different CR diets: classic CR vs ketosis-inducing diets, including Intermittent Fasting (IF), Classic Ketogenic Diet (CKD), Fasting Mimicking Diet (FMD), Very-Low-Calorie Ketogenic Diet (VLCKD) and Spanish Ketogenic Mediterranean Diet (SKMD). Special emphasis on Insulin Resistance (IR) was placed, as it mediates Metabolic Syndrome (MS), a risk factor for CNCD, and predicts MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.

Time makes histone H3 modifications drift

To disclose the epigenetic drift of time passing, we determined the genome-wide distributions of mono- and tri-methylated lysine 4 and acetylated and tri-methylated lysine 27 of histone H3 in the livers of healthy 3, 6 and 12 months old C57BL/6 mice. The comparison of different age profiles of histone H3 marks revealed global redistribution of histone H3 modifications with time, in particular in intergenic regions and near transcription start sites, as well as altered correlation between the profiles of different histone modifications. Moreover, feeding mice with caloric restriction diet, a treatment known to retard aging, preserved younger state of histone H3 in these genomic regions.

Early-life undernutrition induces enhancer RNA remodeling in mice liver

Background Maternal protein restriction diet (PRD) increases the risk of metabolic dysfunction in adulthood, the mechanisms during the early life of offspring are still poorly understood. Apart from genetic factors, epigenetic mechanisms are crucial to offer phenotypic plasticity in response to environmental situations and transmission. Enhancer-associated noncoding RNAs (eRNAs) transcription serves as a robust indicator of enhancer activation, and have potential roles in mediating enhancer functions and gene transcription. Results Using global run-on sequencing (GRO-seq) of nascent RNA including eRNA and total RNA sequencing data, we show that early-life undernutrition causes remodeling of enhancer activity in mouse liver. Differentially expressed nascent active genes were enriched in metabolic pathways. Besides, our work detected a large number of high confidence enhancers based on eRNA transcription at the ages of 4 weeks and 7 weeks, respectively. Importantly, except for ~ 1000 remodeling enhancers, the early-life undernutrition induced instability of enhancer activity which decreased in 4 weeks and increased in adulthood. eRNA transcription mainly contributes to the regulation of some important metabolic enzymes, suggesting a link between metabolic dysfunction and enhancer transcriptional control. We discovered a novel eRNA that is positively correlated to the expression of circadian gene Cry1 with increased binding of epigenetic cofactor p300. Conclusions Our study reveals novel insights into mechanisms of metabolic dysfunction. Enhancer activity in early life acts on metabolism-associated genes, leading to the increased susceptibility of metabolic disorders.

Comparative Effects of Calorie Restriction on Health Span and Insulin Resistance: Classic Calorie Restriction Diet vs Ketosis-Inducing Diet

As Chronic Non-Communicable Diseases (CNCD) increase, preventive approaches become more crucial. In this review, Calorie Restriction (CR) effects on human beings were evaluated, comparing benefits and risks of different CR diets: classic CR vs ketosis-inducing diets, including Intermittent Fasting (IF), Classic Ketogenic Diet (CKD), Fasting Mimicking Diet (FMD), Very-Low-Calorie Ketogenic Diet (VLCKD) and Spanish Ketogenic Mediterranean Diet (SKMD). Special emphasis on Insulin Resistance (IR) was placed, as it mediates Metabolic Syndrome (MS), a risk factor for CNCD, and predicts MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.