Heart Attack, Stroke, Diabetes Could Be Avoided Through a Healthy Gut Microbiome

Heart Attack, Stroke, Diabetes Could Be Avoided Through a Healthy Gut Microbiome

A new study entitled “Intestinal Epithelial Cell Toll-like Receptor 5 Regulates the Intestinal Microbiota to Prevent Low-Grade Inflammation and Metabolic Syndrome in Mice,” suggests that maintaining a healthy gut microbiome, the population of microorganisms that populate the intestine, can prevent metabolic syndrome, thus reducing the risk of developing metabolic-associated syndromes, such as heart attacks, stroke, and diabetes. The study was published in the journal Gastroenterology.

Metabolic syndrome is a condition where there is an imbalance of energy that is stored versus its utilization and is diagnosed in those who exhibit three out of the following five factors: abdominal obesity, high blood pressure, elevated fasting plasma glucose, high blood triglycerides, and low high-density cholesterol (HDL) levels.

Here, the authors generated mice who lacked a key protein of the innate immune system – Toll-like receptor (TLR) 5 (TLR5) – but only in the intestinal epithelium and in a population of dendritic cells (CD11c+ cells). TLR5 is a receptor that recognizes a key component of bacteria, flagellin, and triggers an innate immune response. The authors asked whether the loss of a specific gene of the innate immune response, the Tlr5 gene, results in altered microbiome composition, and leads to the development of chronic inflammatory diseases.

The team of researchers led by Dr. Andrew Gewirtz, a professor at the Institute for Biomedical Sciences at Georgia State, Dr. Benoit Chassaing, a post-doctoral fellow at Georgia State, and Dr. Ruth Ley of the departments of Microbiology and Molecular Biology at Cornell showed that TLR5 expressed by intestinal epithelium cells is capable of regulating the microbiome composition and localization within the gut, and is important in preventing enteric inflammation.

Dr. Andrew Gewirtz noted, “These results suggest that developing a means to promote a healthier microbiota can treat or prevent metabolic disease. They confirm the concept that altered microbiota can promote low-grade inflammation and metabolic syndrome and advance the underlying mechanism. We showed that the altered bacterial population is more aggressive in infiltrating the host and producing substances, namely flagellin and lipopolysaccharide, that further promote inflammation. We’ve filled in a lot of the details about how it works. It’s the loss of TLR5 on the epithelium, the cells that line the surface of the intestine and their ability to respond quickly to bacteria. That ability goes away and results in a more aggressive bacterial population that gets closer in and produces substances that drive inflammation.”

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