Global branches and local states of the human gut microbiome define associations with environmental and intrinsic factors.

The gut microbiome is important for human health, yet modulation requires more insight into inter-individual variation. Here, we explored latent structures of the human gut microbiome across the human lifespan, applying partitioning, pseudotime, and ordination approaches to >35,000 samples. Specifically, three major gut microbiome branches were identified, within which multiple partitions were observed in adulthood, with differential abundances of species along branches.

Gut microbiota and fermentation-derived branched chain hydroxy acids mediate health benefits of yogurt consumption in obese mice.

Meta-analyses suggest that yogurt consumption reduces type 2 diabetes incidence in humans, but the molecular basis of these observations remains unknown. Here we show that dietary yogurt intake preserves whole-body glucose homeostasis and prevents hepatic insulin resistance and liver steatosis in a dietary mouse model of obesity-linked type 2 diabetes. Fecal microbiota transplantation studies reveal that these effects are partly linked to the gut microbiota.

A Fermented Milk Product Containing CNCM I-2494 Improves the Tolerance of a Plant-Based Diet in Patients with Disorders of Gut-Brain Interactions.

Healthy, plant-based diets, rich in fermentable residues, may induce gas-related symptoms. The aim of this exploratory study was to assess the effects of a fermented milk product, containing probiotics, on the tolerance of a healthy diet in patients with disorders of gut-brain interactions (DGBI), complaining of excessive flatulence. In an open design, a 3-day healthy, mostly plant-based diet was administered to patients with DGBI (52 included, 43 completed) before and at the end of 28 days of consumption of a fermented milk product (FMP) containing subsp.

A posteriori dietary patterns better explain variations of the gut microbiome than individual markers in the American Gut Project.

Background: Individual diet components and specific dietary regimens have been shown to impact the gut microbiome.

Objectives: Here, we explored the contribution of long-term diet by searching for dietary patterns that would best associate with the gut microbiome in a population-based cohort.

Methods: Using a priori and a posteriori approaches, we constructed dietary patterns from an FFQ completed by 1800 adults in the American Gut Project.

Diet and gut microbiome interactions of relevance for symptoms in irritable bowel syndrome.

Background: While several studies have documented associations between dietary habits and microbiota composition and function in healthy individuals, no study explored these associations in patients with irritable bowel syndrome (IBS), and especially with symptoms.

Methods: Here, we used a novel approach that combined data from a 4-day food diary, integrated into a food tree, together with gut microbiota (shotgun metagenomic) for individuals with IBS (N = 149) and healthy controls (N = 52). Paired microbiota and food-based trees allowed us to detect new associations between subspecies and diet.

A Fermented Milk Product with CNCM I-2494 and Lactic Acid Bacteria Improves Gastrointestinal Comfort in Response to a Challenge Diet Rich in Fermentable Residues in Healthy Subjects.

Background: Healthy plant-based diets rich in fermentable residues may induce gas-related symptoms. Our aim was to determine the potential of a fermented milk product with probiotics in improving digestive comfort with such diets.

Methods: In an open design, a 3-day high-residue diet was administered to healthy subjects ( = 74 included, = 63 completed) before and following 28 days consumption of a fermented milk product (FMP) containing subsp.

The potential probiotic Lactobacillus rhamnosus CNCM I-3690 strain protects the intestinal barrier by stimulating both mucus production and cytoprotective response.

The gut barrier plays an important role in human health. When barrier function is impaired, altered permeability and barrier dysfunction can occur, leading to inflammatory bowel diseases, irritable bowel syndrome or obesity. Several bacteria, including pathogens and commensals, have been found to directly or indirectly modulate intestinal barrier function.

Droplet digital PCR improves absolute quantification of viable lactic acid bacteria in faecal samples.

Analysing correlations between the observed health effects of ingested probiotics and their survival in digestive tract allows adapting their preparations for food. Tracking ingested probiotic in faecal samples requires accurate and specific tools to quantify live vs dead cells at strain level. Traditional culture-based methods are simpler to use but they do not allow quantifying viable but non-cultivable (VBNC) cells and they are poorly discriminant below the species level.

Basophils from allergic patients are neither hyperresponsive to activation signals nor hyporesponsive to inhibition signals.

Background: Basophil activation contributes to inflammatory reactions, especially in allergy. It is controlled, both positively and negatively, by several mechanisms. High-affinity IgE receptors (FcεRI) generate a mixture of activation and inhibition signals when aggregated, the ratio of which depends on the concentration of allergen recognized by receptor-bound IgE.

Individual strains of Lactobacillus paracasei differentially inhibit human basophil and mouse mast cell activation.

Introduction: The microbiota controls a variety of biological functions, including immunity, and alterations of the microbiota in early life are associated with a higher risk of developing allergies later in life. Several probiotic bacteria, and particularly lactic acid bacteria, were described to reduce both the induction of allergic responses and allergic manifestations. Although specific probiotic strains were used in these studies, their protective effects on allergic responses also might be common for all lactobacilli.

A Dietary Supplement Containing Cinnamon, Chromium and Carnosine Decreases Fasting Plasma Glucose and Increases Lean Mass in Overweight or Obese Pre-Diabetic Subjects: A Randomized, Placebo-Controlled Trial.

Background: Preventing or slowing the progression of prediabetes to diabetes is a major therapeutic issue.

Objectives: Our aim was to evaluate the effects of 4-month treatment with a dietary supplement containing cinnamon, chromium and carnosine in moderately obese or overweight pre-diabetic subjects, the primary outcome being change in fasting plasma glucose (FPG) level. Other parameters of plasma glucose homeostasis, lipid profile, adiposity and inflammatory markers were also assessed.

Jejunal T Cell Inflammation in Human Obesity Correlates with Decreased Enterocyte Insulin Signaling.

In obesity, insulin resistance is linked to inflammation in several tissues. Although the gut is a very large lymphoid tissue, inflammation in the absorptive small intestine, the jejunum, where insulin regulates lipid and sugar absorption is unknown. We analyzed jejunal samples of 185 obese subjects stratified in three metabolic groups: without comorbidity, suffering from obesity-related comorbidity, and diabetic, versus 33 lean controls.

Type 2 Diabetes Remission After Gastric Bypass: What Is the Best Prediction Tool for Clinicians?

Background: Statistical models and scores have been recently suggested to predict remission of type 2 diabetes after bypass surgery, but their relevance in routine clinical practice still needs evaluation. Our objective was to assess these methods on a French cohort and to compare them with other easy-to-use models.

Methods: We investigated a cohort of 84 diabetic obese subjects who underwent Roux-en-Y gastric bypass surgery.

Dietary patterns differently associate with inflammation and gut microbiota in overweight and obese subjects.

Background: Associations between dietary patterns, metabolic and inflammatory markers and gut microbiota are yet to be elucidated.

Objectives: We aimed to characterize dietary patterns in overweight and obese subjects and evaluate the different dietary patterns in relation to metabolic and inflammatory variables as well as gut microbiota.

Design: Dietary patterns, plasma and adipose tissue markers, and gut microbiota were evaluated in a group of 45 overweight and obese subjects (6 men and 39 women).

Adipocyte size threshold matters: link with risk of type 2 diabetes and improved insulin resistance after gastric bypass.

Context: Adipocyte volume has been associated with insulin resistance and type 2 diabetes.

Objective: Our purpose was to identify an adipocyte volume threshold linked with increased insulin resistance risk, and to examine its association with insulin resistance improvement after bariatric surgery.

Setting And Design: We investigated two cohorts of Caucasian women, candidates for bariatric surgery, from two institutional centers in France (age 42.

Dietary intervention impact on gut microbial gene richness.

Complex gene-environment interactions are considered important in the development of obesity. The composition of the gut microbiota can determine the efficacy of energy harvest from food and changes in dietary composition have been associated with changes in the composition of gut microbial populations. The capacity to explore microbiota composition was markedly improved by the development of metagenomic approaches, which have already allowed production of the first human gut microbial gene catalogue and stratifying individuals by their gut genomic profile into different enterotypes, but the analyses were carried out mainly in non-intervention settings.

Human epicardial adipose tissue induces fibrosis of the atrial myocardium through the secretion of adipo-fibrokines.

Aims: Recent studies have reported a relationship between the abundance of epicardial adipose tissue (EAT) and the risk of cardiovascular diseases including atrial fibrillation (AF). However, the underlying mechanisms are unknown. The aim of this study was to examine the effects of the secretome of human EAT on the histological properties of the myocardium.

Roles of chemokine ligand-2 (CXCL2) and neutrophils in influencing endothelial cell function and inflammation of human adipose tissue.

The hypertrophied white adipose tissue (WAT) during human obesity produces inflammatory mediators, including cytokines (IL-6 and TNFα) and chemokines ([C-C motif] chemokine ligand 2 and IL-8). These inflammatory factors are preferentially produced by the nonadipose cells, particularly the adipose tissue infiltrating macrophages. We identified the chemokine (C-X-C motif) ligand 2 (CXCL2) by a transcriptomic approach.

Homozygous leptin receptor mutation due to uniparental disomy of chromosome 1: response to bariatric surgery.

Context: Severe early-onset obesity with major hyperphagia associated with hypogonadotropic hypogonadism is recognized as the main clinical presentation of leptin (LEP) or LEP receptor (LEPR) gene complete deficiency. In a few reported cases, homozygous mutations have been found in patients from consanguineous families. Care of LEPR-deficient patients is complicated because they cannot benefit from LEP treatment.

Differential effects of macronutrient content in 2 energy-restricted diets on cardiovascular risk factors and adipose tissue cell size in moderately obese individuals: a randomized controlled trial.

Background: The most effective and safe dietary approach for weight loss and its impact on the metabolic functions and morphology of adipose tissue remain unclear.

Objectives: We evaluated whether an energy-restricted high-protein diet with a low glycemic index and soluble fiber (LC-P-LGI) would be more effective than a low-calorie conventional diet (LC-CONV) on weight loss and related metabolic risk factors. We further determined factors that may influence adipocyte size during energy restriction.

GLUT2 accumulation in enterocyte apical and intracellular membranes: a study in morbidly obese human subjects and ob/ob and high fat-fed mice.

Objective: In healthy rodents, intestinal sugar absorption in response to sugar-rich meals and insulin is regulated by GLUT2 in enterocyte plasma membranes. Loss of insulin action maintains apical GLUT2 location. In human enterocytes, apical GLUT2 location has not been reported but may be revealed under conditions of insulin resistance.

HMM-Kalign: a tool for generating sub-optimal HMM alignments.

Recent development of strategies using multiple sequence alignments (MSA) or profiles to detect remote homologies between proteins has led to a significant increase in the number of proteins whose structures can be generated by comparative modeling methods. However, prediction of the optimal alignment between these highly divergent homologous proteins remains a difficult issue. We present a tool based on a generalized Viterbi algorithm that generates optimal and sub-optimal alignments between a sequence and a Hidden Markov Model.