Scientist gets $2 million grant to study how inflammation, gut microbiota promote metabolic syndrome

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Credit: Georgia State University

ATLANTA–Dr. Andrew Gewirtz, a professor in the Institute for Biomedical Sciences at Georgia State University, has received a four-year federal grant just over $2 million to study how inflammation and altered gut microbiota, the microorganisms living in the intestine, influence the development of a group of diseases referred to as metabolic syndrome.

Between 50 to 80 million Americans suffer from metabolic syndrome, an epidemic of interrelated obesity-associated disorders including insulin resistance, hyperglycemia (high blood sugar), hyperlipidemia (high cholesterol) and hepatic steatosis (fatty liver). Many of these individuals will develop serious, costly diseases such as type 2 diabetes, cardiovascular disease and liver failure.

The grant from the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases will be used to understand the mechanisms that drive metabolic syndrome and pave the way to developing novel means to combat this public health emergency.

Metabolic syndrome is associated with chronic, low-grade inflammation that interferes with an array of metabolic signaling pathways, including those for insulin and leptin (a hormone released from fat cells that helps regulate energy balance and reduce hunger). Chronic low-grade inflammation promotes metabolic syndrome.

“Better understanding of the underlying causes of low-grade inflammation is germane to managing the metabolic syndrome epidemic,” Gewirtz said.

In previous work, Gewirtz and his team found that low-grade inflammation can originate from poor management of gut microbiota. They hypothesized that alterations in microbiota promote low-grade inflammation and metabolic syndrome, which is applicable to understanding how diet, particularly industrialization of the food supply, might be altering the microbiota-host relationship and promoting these health issues.

They’ve found that a central feature of metabolic syndrome in mice and humans is bacteria infiltrating the normally near-sterile inner mucus layer of the intestine. This microbiota encroachment can activate pro-inflammatory signaling of the intestine and result in bacteria and their products moving into liver and adipose (fat) tissue, driving low-grade inflammation in these organs. In studies, obese humans who lacked microbiota encroachment also didn’t have metabolic syndrome.

“Together, these results underscore our central hypothesis that microbiota encroachment is a pivotal event in driving low-grade inflammation and subsequently metabolic syndrome,” Gewirtz said. “This hypothesis holds that preventing or reversing microbiota encroachment will ameliorate metabolic syndrome.”

In collaboration with Dr. Shanthi Srinivasan of Emory University, this study proposes to identify encroaching bacteria. The project will also define how encroaching bacteria drive low-grade inflammation and affect metabolism, as well as develop a means to train the immune system to reduce microbiota encroachment and improve metabolic syndrome.

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For more information about the grant, visit https://projectreporter.nih.gov/project_info_description.cfm?aid=10151289&icde=53915102.

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Original Source

https://news.gsu.edu/2021/03/17/biomedical-sciences-researcher-receives-2-million-federal-grant-to-study-how-inflammation-altered-gut-microbiota-promote-metabolic-syndrome/

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