Duodenal Anaerobutyricum soehngenii 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 Anaerobutyricum soehngenii to be associated with improved insulin sensitivity in subjects with MetS. In this proof-of-concept study, we investigated the potential therapeutic effects of A. soehngenii L2-7 on systemic metabolic responses and duodenal transcriptome profiles in individuals with MetS. DESIGN: In this randomised double-blind placebo-controlled cross-over study, 12 male subjects with MetS received duodenal infusions of A. soehngenii/ placebo and underwent duodenal biopsies, mixed meal tests (6 hours postinfusion) and 24-hour continuous glucose monitoring. RESULTS: A. soehngenii treatment provoked a markedly increased postprandial excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) and an elevation of plasma secondary bile acids, which were positively associated with GLP-1 levels. Moreover, A. soehngenii treatment robustly shaped the duodenal expression of 73 genes, with the highest fold induction in the expression of regenerating islet-protein 1B (REG1B)-encoding gene. Strikingly, duodenal REG1B expression positively correlated with GLP-1 levels and negatively correlated with peripheral glucose variability, which was significantly diminished in the 24 hours following A. soehngenii intake. Mechanistically, Reg1B expression is induced upon sensing butyrate or bacterial peptidoglycan. Importantly, A. soehngenii duodenal administration was safe and well tolerated. CONCLUSIONS: A single dose of A. soehngenii improves peripheral glycaemic control within 24 hours; it specifically stimulates intestinal GLP-1 production and REG1B expression. Further studies are needed to delineate the specific pathways involved in REG1B induction and function in insulin sensitivity. TRIAL REGISTRATION NUMBER: NTR-NL6630.

Overweight and Obesity Are Associated With Acute Kidney Injury and Acute Respiratory Distress Syndrome, but Not With Increased Mortality in Hospitalized COVID-19 Patients: A Retrospective Cohort Study.

Objective: To evaluate the association between overweight and obesity on the clinical course and outcomes in patients hospitalized with COVID-19. Design: Retrospective, observational cohort study. Methods: We performed a multicenter, retrospective, observational cohort study of hospitalized COVID-19 patients to evaluate the associations between overweight and obesity on the clinical course and outcomes. Results: Out of 1634 hospitalized COVID-19 patients, 473 (28.9%) had normal weight, 669 (40.9%) were overweight, and 492 (30.1%) were obese. Patients who were overweight or had obesity were younger, and there were more women in the obese group. Normal-weight patients more often had pre-existing conditions such as malignancy, or were organ recipients. During admission, patients who were overweight or had obesity had an increased probability of acute respiratory distress syndrome [OR 1.70 (1.26-2.30) and 1.40 (1.01-1.96)], respectively and acute kidney failure [OR 2.29 (1.28-3.76) and 1.92 (1.06-3.48)], respectively. Length of hospital stay was similar between groups. The overall in-hospital mortality rate was 27.7%, and multivariate logistic regression analyses showed that overweight and obesity were not associated with increased mortality compared to normal-weight patients. Conclusion: In this study, overweight and obesity were associated with acute respiratory distress syndrome and acute kidney injury, but not with in-hospital mortality nor length of hospital stay.

Striatal Dopamine Transporter Availability Is Not Associated with Food Craving in Lean and Obese Humans; a Molecular Imaging Study.

Brain dopamine signaling is essential for the motivation to eat, and obesity is associated with altered dopaminergic signaling and increased food craving. We used molecular neuroimaging to explore whether striatal dopamine transporter (DAT) availability is associated with craving as measured with the General Food Craving Questionnaire-Trait (G-FCQ-T). We here show that humans with obesity (n = 34) experienced significantly more craving for food compared with lean subjects (n = 32), but food craving did not correlate significantly with striatal DAT availability as assessed with 123I-FP-CIT single-photon emission computed tomography. We conclude that food craving is increased in obesity, but the scores for food craving are not related to changes in striatal DAT availability.

Plasma Imidazole Propionate Is Positively Correlated with Blood Pressure in Overweight and Obese Humans.

BACKGROUND: The gut microbiota and its metabolites are essential for host health and dysbiosis has been involved in several pathologic conditions such as type 2 diabetes (T2D) and cardiovascular disease (CVD). Recent studies have identified that plasma imidazole propionate (ImP), a microbial-produced metabolite, is increased in patients with prediabetes and T2D. More recently, ImP was found to be significantly increased in patients with overt CVD. Here, we aimed to investigate the association between ImP and CVD risk factors: blood pressure, HDL-cholesterol, LDL-cholesterol and insulin-resistance in overweight and obese subjects without T2D or use of any metabolic diseases-related medication. METHODS: Plasma metabolites, including ImP, were determined in 107 male or post-menopausal women with overweight/obesity, but without T2D. Insulin-sensitivity was assessed with the gold standard method: the hyperinsulinemic-euglycemic clamp using the isotope [6,6-2H2] glucose and expressed as glucose rate of disposal (Rd) for peripheral insulin sensitivity and suppression of endogenous glucose production (EGP) for hepatic insulin sensitivity. RESULTS: Partial correlation analysis controlled for BMI and age showed a significant correlation between ImP and diastolic blood pressure (rs = 0.285, p = 0.004) and a borderline significance with systolic blood pressure (rs = 0.187, p = 0.060); however, systolic and diastolic blood pressure did not correlate with ImP precursor histidine (rs = 0.063, p = 0.526 and r = -0.038, p = 0.712, respectively). We did not find a correlation between ImP with LDL-cholesterol or HDL-cholesterol (rs = -0.181, p = 0.064 and rs = 0.060, p = 0.546, respectively). Furthermore, there was no association between plasma ImP concentrations and Rd and EGP suppression. CONCLUSION: In this cohort with overweight/obese subjects without T2D, plasma ImP concentrations were positively correlated with diastolic blood pressure but not with insulin-sensitivity.

The Role of the Gut Microbiota in the Gut-Brain Axis in Obesity: Mechanisms and Future Implications.

Interaction between the gut and the brain is essential for energy homeostasis. In obesity, this homeostasis is disrupted, leading to a positive energy balance and weight gain. Obesity is a global epidemic that affects individual health and strains the socioeconomic system. Microbial dysbiosis has long been reported in obesity and obesity-related disorders. More recent literature has focused on the interaction of the gut microbiota and its metabolites on human brain and behavior. Developing strategies that target the gut microbiota could be a future approach for the treatment of obesity. Here, we review the microbiota-gut-brain axis and possible therapeutic options.