SC Connecticut News

Li Wen, MD, PhD, professor of medicine (endocrinology) at Yale School of Medicine, is investigating how changes in gut composition influenced by innate immunity affect health. Through her research using preclinical models, she discovered that gut microbiota plays a significant role in type 1 diabetes. Recently, she found that the loss of a specific innate immunity receptor in B cells leads to changes in gut bacteria linked to the development of obesity.

More than two in five U.S. adults have obesity, which increases their risk for other serious diseases, according to the U.S. Centers for Disease Control and Prevention. Wen notes that some health issues associated with obesity include type 2 diabetes, cardiovascular diseases, and certain cancers. Obesity is also linked with increased medical costs and lower quality of life.

In a Q&A session, Wen discusses how gut bacteria become “good” or “bad,” the connection between gut composition and obesity, and the use of gut microbiota to address this growing health challenge.

What is gut microbiota?

"Microorganisms live in our guts. Most of these microorganisms are bacteria, but there are also viruses and fungi. So gut microbiota includes bacteria, viruses, and fungi."

How does gut microbiota become “good” or “bad”?

"Our guts are a complex ecosystem with trillions of bacteria, and these bacteria have both symbiotic and competitive relationships. Some depend on each other. For example, one type of bacteria might produce something necessary for another’s survival. Other types of bacteria kill each other to grow.

The system is usually relatively balanced. However, many factors can affect this balance, including a person’s lifestyle, diet, medication, and immune system."

How can gut bacteria influence the development of obesity and type 2 diabetes?

"Harmful bacteria have a common feature: they stick to epithelial cells that line the gut wall and loosen the way these cells stick to each other. When this happens, many things that are meant to be contained in the gut leak into the bloodstream including lipopolysaccharides—a major type of endotoxin that can cause inflammation. Inflammation in the body can cause changes in metabolism and gut microbiota leading to obesity and type 2 diabetes. Individuals with obesity or type 2 diabetes often have elevated levels of this endotoxin in their bloodstream.

Changes in gut composition affect the immune system. The intestine is protected by many different types of immune cells including B lymphocytes. B lymphocytes express the innate immune receptor TLR9 which recognizes bacterial DNA. In a recent study when we removed TLR9 in B cells in preclinical models we observed altered gut bacteria that worsened obesity. Interestingly we found that gut bacteria alone could transfer obesity from one preclinical model to another. Our study adds new evidence about the importance of the immune system in regulating gut bacteria and metabolism."

How can we use gut microbiota to prevent or treat obesity?

"The most common way to prevent obesity through gut bacteria is to add more fiber probiotics and prebiotics to the diet through food or supplements to increase good bacteria.

Research shows that exercise can also positively change gut microbiota.

Studies are ongoing on treating obesity with fecal microbiota transplantation where bacteria from healthy stool are used to restore microbiota balance in patients with dysbiosis.

There isn’t one silver bullet that will correct or cure this complex issue; Gut microbiota is one approach among others such as dietary interventions exercise pharmacotherapy and bariatric surgery; The best way to manage obesity is using complementary strategies."

Yale School of Medicine’s Section of Endocrinology & Metabolism works towards improving health outcomes for individuals with endocrine & metabolic diseases by advancing scientific knowledge applying new information into patient care & training future physicians & scientists as leaders within their field.