National Institutes of Health Fund NYU School of Dentistry’s Investigation Into Inflammation

It seems like every day new discoveries are being made regarding the cause and effect of inflammation. This is pertinent to dentistry at least in part in because chronic systemic inflammation is known to play a role in the development of periodontal diseases. Likewise, periodontal diseases have been shown to contribute to chronic inflammation by triggering a systemic inflammatory response.

To help solve this puzzle, the National Institute on Aging, part of the National Institutes of Health, recently awarded researchers at New York University College of Dentistry (NYU Dentistry) a 5-year grant of $2.4 million. The funds will be used to investigate the relationship between low-grade inflammation and aging, otherwise known as “inflammaging.”

INFLAMMAGING AND THE GUT

Inflammaging, which simmers in the background, turning up the heat as a person ages, is said to play an important role in not only aging but age-related conditions such as diabetes and heart disease. In fact, it is reported to interfere with tissue repair and foster degeneration.

This type of inflammation is thought to result from a skewed relationship between the immune system and an imbalanced gut microbiome. Microbiota in the gut play a central role in inflammaging due in part to their ability to release inflammatory substances.¹

According to principal investigator Xin Li, PhD, associate professor of molecular pathology at NYU Dentistry, the study aims to enhance understanding of how the aging microbiome relates to causes and pathophysiology of age-related chronic inflammation. In fact, the NYU researchers recently discovered a link between aging and an elevation in a signaling metabolite called succinate.²

THE ROLE OF SUCCINATE

Succinate, a salt or ester of succinic acid, plays a vital role in regulating intestinal inflammation, energy metabolism, and relaying messaging throughout the body. The research team will explore the impact of succinate elevation on the gut microbiome in animal models, noting changes and how these changes regulate signaling to promote inflammation.

Elevated levels of succinate alter the gut microbiome by increasing the abundance of disease-causing organisms. It also activates the succinate receptor to increase inflammation and the production of myeloid lineage in the bone marrow. Preliminary data from Li’s team shows that the interplay among gut microbes, altered metabolites, and the activation of succinate receptor contributes to inflammaging.²

RESET FOR THE GUT

The hope is to “reprogram” the gut’s microbiome by using antibiotics and fecal transplants to see if this alters the inflammation. Fecal transplants, though involving a kind of “ick” factor, has been used to successfully treat Clostridium difficile infection, which causes conditions such as diarrhea and colitis. It reportedly shows promise for treating other conditions throughout the body.

Through a transfer of a processed mix of stool from a healthy donor to a patient’s intestines, the aim is to introduce beneficial bacteria so that a healthy bacterial balance in the gut can be restored to help fight infection.

The research team also plans to study the role of bone marrow in succinate-stimulated inflammation and the myeloid lineage shift. According to Li, they hope to enhance understanding of the relationship between the aging microbiome and age-related chronic inflammation. Says Li, “If we find that targeting the gut microbiome and succinate receptor activation can alleviate inflammaging, this could provide us with novel targets for treating age-related inflammation.”²

References

1. Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nature Reviews Endocrinology. 2018;14:576–590.
2. New York University (NYU). NYU Dentistry Receives $2.4 Million Grant to Study Low-Grade Inflammation in Aging. Click here to read.