Background Intestinal microbiota and their metabolites (e.g. short-chain fatty acids (SCFAs)) may influence nonalcoholic fatty liver disease (NAFLD). Objective The objective of this article is to analyze gut bacterial diversity together with fecal SCFA concentrations and immunophenotyping of peripheral blood in histology-proven NAFLD patients. Methods Thirty-two NAFLD patients (14 nonalcoholic fatty liver (NAFL), 18 nonalcoholic steatohepatitis (NASH)) and 27 healthy controls (HCs)) were included in this study. Bacterial communities in feces were profiled by 16S ribosomal RNA gene sequencing of the V3–V4 region. Fecal SCFA levels were analyzed by high-performance liquid chromatography. Fluorescence-activated cell sorting analysis was performed of peripheral blood mononuclear cells. Results NASH patients were characterized by higher abundance of Fusobacteria and Fusobacteriaceae compared to NAFL and HCs. Conforming to our finding that NAFLD patients had higher fecal acetate and propionate levels, taxonomical differences of fecal bacteria were dominated by SCFA-producing bacteria. Higher fecal propionate and acetate levels were associated with lower resting regulatory T-cells (rTregs) (CD4+CD45RA+CD25++) as well as higher Th17/rTreg ratio in peripheral blood as immunological characteristics of NASH patients. Conclusions NASH patients are characterized by a different gut microbiome composition with higher fecal SCFA levels and higher abundance of SCFA-producing bacteria in NAFLD. These changes are associated with immunological features of disease progression. Our data suggest an important role of the intestinal microbiome and immunomodulatory bacterial metabolites in human NAFLD.
Background The novel coronavirus disease 2019 , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has escalated rapidly to a global pandemic stretching healthcare systems worldwide to their limits. Surgeons have had to immediately react to this unprecedented clinical challenge by systematically repurposing surgical wards. Purpose To provide a detailed set of guidelines developed in a surgical ward at University Hospital Wuerzburg to safely accommodate the exponentially rising cases of SARS-CoV-2 infected patients without compromising the care of emergency surgery and oncological patients or jeopardizing the well-being of hospital staff. Conclusions The dynamic prioritization of SARS-CoV-2 infected and surgical patient groups is key to preserving life while maintaining high surgical standards. Strictly segregating patient groups in emergency rooms, non-intensive care wards and operating areas prevents viral spread while adequately training and carefully selecting hospital staff allow them to confidently and successfully undertake their respective clinical duties.
Bariatric surgery remains the single most effective long-term treatment modality for morbid obesity, achieved mainly by lowering caloric intake through as yet ill-defined mechanisms. Here we show in rats that Roux-en-Y gastric bypass (RYGB)-like rerouting of ingested fat mobilizes lower small intestine production of the fat-satiety molecule oleoylethanolamide (OEA). This was associated with vagus nerve-driven increases in dorsal striatal dopamine release. We also demonstrate that RYGB upregulates striatal dopamine 1 receptor (D1R) expression specifically under high-fat diet feeding conditions. Mechanistically, interfering with local OEA, vagal, and dorsal striatal D1R signaling negated the beneficial effects of RYGB on fat intake and preferences. These findings delineate a molecular/systems pathway through which bariatric surgery improves feeding behavior and may aid in the development of novel weight loss strategies that similarly modify brain reward circuits compromised in obesity.
Roux-en-Y gastric bypass (RYGB) and duodenal jejunal bypass (DJB), two different forms of bariatric surgery, are associated with improved glucose tolerance, but it is not clear whether the gut microbiota contributes to this effect. Here we used fa/fa rats as a model of impaired glucose tolerance to investigate whether (i) the microbiota varies between fa/fa and nondiabetic fa/+ rats; (ii) the microbiota of fa/fa rats is affected by RYGB and/or DJB; and (iii) surgically induced microbiota alterations contribute to glucose metabolism. We observed a profound expansion of Firmicutes (specifically, Lactobacillus animalis and Lactobacillus reuteri) in the small intestine of diabetic fa/fa compared with nondiabetic fa/+ rats. RYGB-, but not DJB-, treated fa/fa rats exhibited greater microbiota diversity in the ileum and lower L. animalis and L. reuteri abundance compared with sham-operated fa/fa rats in all intestinal segments, and their microbiota composition resembled that of unoperated fa/+ rats. To investigate the functional role of RYGB-associated microbiota alterations, we transferred microbiota from sham- and RYGB-treated fa/fa rats to germ-free mice. The metabolic phenotype of RYGB-treated rats was not transferred by the transplant of ileal microbiota. In contrast, postprandial peak glucose levels were lower in mice that received cecal microbiota from RYGB- versus sham-operated rats. Thus, diabetes-associated microbiota alterations in fa/fa rats can be modified by RYGB, and modifications in the cecal microbiota may partially contribute to improved glucose tolerance after RYGB.
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