Researcher gets $1.95 million grant to study how gut bacteria cause decline of aging immune system

ATLANTA–Dr. Leszek Ignatowicz, a professor in the Institute for Biomedical Sciences at Georgia State University, has received a five-year, $1.95 million federal grant to study how changes in the microorganisms in the gut, referred to as intestinal microbiota, cause the immune system to decline as organisms get older.

The intestinal microbiota contributes foreign substances that induce immune responses in the body, but it remains unclear how these substances influence the gradual deterioration of the immune system brought on by natural aging, known as immunosenescence, in older mice and humans.

Age-related imbalance in the microbiome is important to understand because it can lead to serious health issues such as digestive disturbances, immune dysfunction and intestinal inflammation.

This grant from the National Institutes of Health’s National Institute on Aging will fund research to develop new strategies to control intestinal inflammation in the elderly, based on therapies that strictly regulate gut microbiota, which will have wide-ranging benefits for health and lifespan. The project will test whether administering a newly developed mini-microbiome can help revitalize an aging immune system in old mice.

“There is a need to develop a standardized microbial flora that has a manageable size and resembles natural microbiome that when administered to old, frail individuals will rebalance their intestinal homeostasis and enhance the function of important immune cells,” Ignatowicz said. “We hypothesize that therapeutic administration of Akkermansia municiphila, a species of bacterium commonly found in the human gut, to old mice can improve tolerance to intestinal microbiota and reduce immunosenescence.”

Supplementing microbiota in elderly people has long been proposed as an anti-immunosenescence treatment. However, only a limited number of bacteria that “revitalize” the aging immune system have been identified, and the mechanisms of their actions remain unclear. A. municiphila has been found capable of rejuvenating the aging immune system by controlling gut integrity and microbiota diversity in mice and humans.

Ignatowicz and his team will investigate how intestinal microbiota, particularly A. municiphila, induces and expands CD4 T cells, which play an important role in the immune system, to produce immune tolerance in old mice. This work could be significant for developing new therapeutic strategies that identify bacteria capable of stimulating an immune response and reprogramming CD4 T cells to control microbial imbalance in elderly people.

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