Biology subjects

Anhe, F. F.

Publications and source records attributed to Anhe, F. F..

3 recordsLinked to original sources

bioRxiv2021

Gut microbiota-based vaccination engages innate immunity to improve blood glucose control in obese mice

Obesity and diabetes increase circulating levels of microbial components derived from the gut microbiota. Individual bacterial factors (i.e., postbiotics) can have opposing effects on metabolic inflammation and blood glucose control. We tested the net effect of gut bacterial extracts on blood glucose using a microbiota-based vaccination strategy in mice. Male and female mice had improved insulin sensitivity and blood glucose control five weeks after a single subcutaneous injection of a specific dose of a bacterial extract obtained from the luminal contents of the proximal gut. Injection of mice with proximal gut extracts from germ-free mice revealed that bacteria were required for a microbiota-based vaccination to improve blood glucose control. Vaccination of Nod1-/-, Nod2-/-, and Ripk2-/- mice showed that each of these innate immune proteins was required for bacterial extract injection to improve blood glucose control. A microbiota-based vaccination promoted a proximal gut immunoglobulin-G (IgG) response directed against bacterial extract antigens, where subcutaneous injection of mice with the luminal contents of the ileum elicited a bacterial extract-specific IgG response that is compartmentalized to the ileum of vaccinated mice. A microbiota-based vaccination was associated with an altered the microbiota composition in the ileum and colon of mice. Lean mice required a single injection of proximal gut bacterial extracts, but high fat diet (HFD)-fed, obese mice required prime-boost bacterial extract injections for improvements in blood glucose control. These data show that, upon subversion of the gut barrier, vaccination with proximal gut bacterial extracts engages innate immunity to promote long-lasting improvements in blood glucose control in a dose-dependent manner.

physiology↗

bioRxiv2021

Metabolic endotoxemia is dictated by the type of lipopolysaccharide

Lipopolysaccharides (LPS) can promote metabolic endotoxemia, which is considered inflammatory and metabolically detrimental based on Toll-like receptor (TLR)4 agonists such as Escherichia coli-derived LPS. LPS from certain bacteria antagonize TLR4 yet contribute to endotoxemia measured by Endotoxin Units (EU). We found that E. coli LPS impaired gut barrier function and worsened glycemic control in mice, but equal doses of LPS from other bacteria did not. Matching the LPS dose from R. sphaeroides and E. coli by EU revealed that only E. coli LPS promoted dysglycemia, adipose inflammation, delayed intestinal glucose absorption, and augmented insulin and GLP-1 secretion. Metabolically beneficial endotoxemia promoted by R. sphaeroides LPS counteracted dysglycemia caused by an equal dose of E. coli LPS and promoted insulin sensitivity in obese mice. The concept of metabolic endotoxemia should be expanded beyond LPS load (EU) to include LPS characteristics, where the balance of deleterious and beneficial endotoxemia regulates host metabolism. HighlightsO_LIType of LPS dictates gut barrier function, inflammation, insulin, GLP-1, intestinal glucose absorption and blood glucose C_LIO_LIEndotoxin Units (EU) do not reflect how LPS influences blood glucose or hormones C_LIO_LILPS derived from certain types of bacteria are insulin sensitizers C_LIO_LIR. sphaeroides LPS promotes metabolically beneficial endotoxemia C_LIO_LILPS characteristics dictate metabolically beneficial versus deleterious endotoxemia C_LI

physiology↗

bioRxiv2020

Gut microbiota impairs insulin clearance during obesity

Hyperinsulinemia can be a cause and consequence of obesity and insulin resistance. Increased insulin secretion and reduced insulin clearance can contribute to hyperinsulinemia. The triggers for changes in insulin clearance during obesity are ill-defined. We found that oral antibiotics mitigated impaired insulin clearance in mice fed a high fat diet (HFD) for 12 weeks or longer. Short-term HFD feeding and aging did not alter insulin clearance in mice. Germ-free mice colonized with microbes from HFD-fed mice had impaired insulin clearance, but not C-peptide clearance, and only after mice were colonized for 6 weeks and then HFD-fed. Five bacterial taxa predicted >90% of the variance in insulin clearance. Our data indicate that gut microbes are an independent and transmissible factor that regulates obesity-induced changes in insulin clearance. A small cluster of microbes may be a target for mitigating defects in insulin clearance and the progression of obesity and Type 2 Diabetes. We propose that a small community in the gut microbiota can impair insulin clearance and increase insulin load and the risk of complications from hyperinsulinemia.

physiology↗