Gut bacterium Intestinimonas butyriciproducens improves host metabolic health: evidence from cohort and animal intervention studies.

Background: The human gut microbiome strongly influences host metabolism by fermenting dietary components into metabolites that signal to the host. Our previous work has shown that Intestinimonas butyriciproducens is a prevalent commensal bacterium with the unique ability to convert dietary fructoselysine to butyrate, a well-known signaling molecule with proven health benefits. Dietary fructoselysine is an abundant Amadori product formed in foods during thermal treatment and is part of foods rich in dietary advanced glycation end products which have been associated with cardiometabolic disease.

From Endoscopic Inspection to Gene-Expression: A Thorough Assessment of the Duodenal Mucosa After Resurfacing-A Prospective Study.

Aims: Duodenal Mucosal Resurfacing (DMR) is an endoscopic ablation technique aimed at improving glycemia in patients with type 2 diabetes mellitus (T2DM). Although the exact underlying mechanism is still unclear, it is postulated that the DMR-induced improvements are the result of changes in the duodenal mucosa. For this reason, we assessed macroscopic and microscopic changes in the duodenal mucosa induced by DMR + GLP-1RA.

Kinetics of imidazole propionate from orally delivered histidine in mice and humans.

Imidazole Propionate (ImP), a gut-derived metabolite from histidine, affects insulin signaling in mice and is elevated in type 2 diabetes (T2D). However, the source of histidine and the role of the gut microbiota remain unclear. We conducted an intervention study in mice and humans, comparing ImP kinetics in mice on a high-fat diet with varying histidine levels and antibiotics, and assessed ImP levels in healthy and T2D subjects with histidine supplementation.

Bacteriophages from treatment-naïve type 2 diabetes individuals drive an inflammatory response in human co-cultures of dendritic cells and T cells.

Individuals with type 2 diabetes (T2D) show signs of low-grade inflammation, which is related to the development of insulin resistance and beta-cell dysfunction. However, the underlying triggers remain unknown. The gut microbiota is a plausible source as it comprises pro-inflammatory bacteria, bacterial metabolites and viruses, including (bacterio)phages.

Effects of Oral Butyrate on Blood Pressure in Patients With Hypertension: A Randomized, Placebo-Controlled Trial.

Background: The microbiota-derived short chain fatty acid butyrate has been shown to lower blood pressure (BP) in rodent studies. Nonetheless, the net effect of butyrate on hypertension in humans remains uncovered. In this study, for the first time, we aimed to determine the effect of oral butyrate on BP in patients with hypertension.

Higher fibre and lower carbohydrate intake are associated with favourable CGM metrics in a cross-sectional cohort of 470 individuals with type 1 diabetes.

Aims/hypothesis: The aim of this work was to investigate the association between macronutrient intakes and continuous glucose monitoring (CGM) metrics in individuals with type 1 diabetes.

Methods: In 470 individuals with type 1 diabetes of the GUTDM1 cohort (65% female, median age 40 [IQR 28-53] years, median diabetes duration 15 [IQR 6-29] years), we used logistic regression to establish associations between macronutrient intakes and the CGM metrics time in range (TIR, time spent between 3.9-10.

Associations between diabetes-related genetic risk scores and residual beta cell function in type 1 diabetes: the GUTDM1 study.

Aims/hypothesis: Use of genetic risk scores (GRS) may help to distinguish between type 1 diabetes and type 2 diabetes, but less is known about whether GRS are associated with disease severity or progression after diagnosis. Therefore, we tested whether GRS are associated with residual beta cell function and glycaemic control in individuals with type 1 diabetes.

Methods: Immunochip arrays and TOPMed were used to genotype a cross-sectional cohort (n=479, age 41.

Can fecal microbiota transplantations modulate autoimmune responses in type 1 diabetes?

Type 1 diabetes (T1D) is a chronic autoimmune disease targeting insulin-producing pancreatic beta cells. T1D is a multifactorial disease incorporating genetic and environmental factors. In recent years, the advances in high-throughput sequencing have allowed researchers to elucidate the changes in the gut microbiota taxonomy and functional capacity that accompany T1D development.

Prevalence and predictive features of metabolic dysfunction-associated steatotic liver disease in type 1 diabetes.

Aims/hypothesis: The prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in type 1 diabetes remain unclear. Therefore, we investigated the prevalence and severity of MASLD in type 1 diabetes and assessed which clinical features are most important in predicting MASLD severity.

Methods: A total of 453 individuals with type 1 diabetes (41.

Intestinal permeability is associated with aggravated inflammation and myofibroblast accumulation in Graves' orbitopathy: the MicroGO study.

Background: Graves' disease (GD) and Graves' orbitopathy (GO) result from ongoing stimulation of the TSH receptor due to autoantibodies acting as persistent agonists. Orbital pre-adipocytes and fibroblasts also express the TSH receptor, resulting in expanded retro-orbital tissue and causing exophthalmos and limited eye movement. Recent studies have shown that GD/GO patients have a disturbed gut microbiome composition, which has been associated with increased intestinal permeability.

Comparative Analysis of Taxonomic and Functional Gut Microbiota Profiles in Relation to Seroconversion of Thyroid Peroxidase Antibodies in Euthyroid Participants.

Previous studies have reported gut microbiome alterations in Hashimoto's autoimmune thyroiditis (HT) patients. Yet, it is unknown whether an aberrant microbiome is present before clinical disease onset in participants susceptible to HT or whether it reflects the effects of the disease itself. In this study, we report for the first time a comprehensive characterization of the taxonomic and functional profiles of the gut microbiota in euthyroid seropositive and seronegative participants.

Protocol for a double-blinded randomised controlled trial to assess the effect of faecal microbiota transplantations on thyroid reserve in patients with subclinical autoimmune hypothyroidism in the Netherlands: the IMITHOT trial.

Background: Hashimoto's thyroiditis (HT) is a common endocrine autoimmune disease affecting roughly 5% of the general population and involves life-long treatment with levothyroxine, as no curative treatment yet exists. Over the past decade, the crosstalk between gut microbiota and the host immune system has been well-recognised, identifying the gut microbiome as an important factor in host health and disease, including susceptibility to autoimmune diseases. Previous observational studies yielded a link between disruption of the gut microbiome composition and HT.

Residual β-Cell Function Is Associated With Longer Time in Range in Individuals With Type 1 Diabetes.

Objective: Little is known about the influence of residual islet function on glycemic control in type 1 diabetes (T1D). We investigated the associations between residual β-cell function and metrics of continuous glucose monitoring (CGM) in individuals with T1D.

Research Design And Methods: In this cross-sectional cohort comprising 489 individuals (64% female, age 41.

Sex differences in associations of plasma metabolites with blood pressure and heart rate variability: The HELIUS study.

Background And Aims: Since plasma metabolites can modulate blood pressure (BP) and vary between men and women, we examined sex differences in plasma metabolite profiles associated with BP and sympathicovagal balance. Our secondary aim was to investigate associations between gut microbiota composition and plasma metabolites predictive of BP and heart rate variability (HRV).

Methods: From the HELIUS cohort, we included 196 women and 173 men.

Gut microbiome in type 1 diabetes: the immunological perspective.

Introduction: Type 1 diabetes (T1D) is a prevalent, and yet uncurable, autoimmune disease targeting insulin-producing pancreatic β-cells. Despite a known genetic component in T1D onset, genetics alone cannot explain the alarming worldwide rise in T1D incidence, which is attributed to a growing impact of environmental factors, including perturbations of the gut microbiome.

Areas Covered: Intestinal commensal bacteria plays a crucial role in host physiology in health and disease by regulating endocrine and immune functions.

Microbial Tryptophan Metabolism Tunes Host Immunity, Metabolism, and Extraintestinal Disorders.

The trillions of commensal microorganisms comprising the gut microbiota have received growing attention owing to their impact on host physiology. Recent advances in our understandings of the host-microbiota crosstalk support a pivotal role of microbiota-derived metabolites in various physiological processes, as they serve as messengers in the complex dialogue between commensals and host immune and endocrine cells. In this review, we highlight the importance of tryptophan-derived metabolites in host physiology, and summarize the recent findings on the role of tryptophan catabolites in preserving intestinal homeostasis and fine-tuning immune and metabolic responses.

Microbial influencers: treating diabetes through the gut.

A recently published study by Bell et al. shows altered immunotolerance in people with type 1 diabetes by dietary supplementation of modified resistant starch fibre.

Levothyroxine use and the risk of colorectal cancer: a large population-based case-control study.

Objective: Whether an association between oral levothyroxine use, leading to supraphysiological exposure of the colon to thyroid hormones, and risk of colorectal cancer exists in humans is unclear. We therefore aimed to assess whether the use of levothyroxine is associated with a reduced risk of colorectal cancer in a linked cohort of pharmacy and cancer data.

Design: Population-based matched case-control study.

Impact of intracellular innate immune receptors on immunometabolism.

Immunometabolism, which is the metabolic reprogramming of anaerobic glycolysis, oxidative phosphorylation, and metabolite synthesis upon immune cell activation, has gained importance as a regulator of the homeostasis, activation, proliferation, and differentiation of innate and adaptive immune cell subsets that function as key factors in immunity. Metabolic changes in epithelial and other stromal cells in response to different stimulatory signals are also crucial in infection, inflammation, cancer, autoimmune diseases, and metabolic disorders. The crosstalk between the PI3K-AKT-mTOR and LKB1-AMPK signaling pathways is critical for modulating both immune and nonimmune cell metabolism.

Duodenal infusion stimulates GLP-1 production, ameliorates glycaemic control and beneficially shapes the duodenal transcriptome in metabolic syndrome subjects: a randomised double-blind placebo-controlled cross-over study.

Objective: Although gut dysbiosis is increasingly recognised as a pathophysiological component of metabolic syndrome (MetS), the role and mode of action of specific gut microbes in metabolic health remain elusive. Previously, we identified the commensal butyrogenic to be associated with improved insulin sensitivity in subjects with MetS. In this proof-of-concept study, we investigated the potential therapeutic effects of L2-7 on systemic metabolic responses and duodenal transcriptome profiles in individuals with MetS.

Effect of Fecal Microbiota Transplantation Combined With Mediterranean Diet on Insulin Sensitivity in Subjects With Metabolic Syndrome.

Background: Recent studies demonstrate that a Mediterranean diet has beneficial metabolic effects in metabolic syndrome subjects. Since we have shown that fecal microbiota transplantation (FMT) from lean donors exerts beneficial effects on insulin sensitivity, in the present trial, we investigated the potential synergistic effects on insulin sensitivity of combining a Mediterranean diet with donor FMT in subjects with metabolic syndrome.

Design: Twenty-four male subjects with metabolic syndrome were put on a Mediterranean diet and after a 2-week run-in phase, the subjects were randomized to either lean donor ( = 12) or autologous ( = 12) FMT.

Auto-immunity and the gut microbiome in type 1 diabetes: Lessons from rodent and human studies.

Type 1 diabetes (T1D) is an auto-immune disease that destructs insulin-producing pancreatic beta-cells within the islets of Langerhans. The incidence of T1D has tripled over the last decades, while the pathophysiology of the disease is still largely unknown. Currently, there is no cure for T1D.