Tuesday, January 12, 2021

To understand periodontal disease, researchers examine the surprising behavior of T cells

FORSYTH INSTITUTE

In diseases characterized by bone loss -such as periodontitis, rheumatoid arthritis, and osteoporosis- there is a lot that scientists still don't understand. What is the role of the immune response in the process? What happens to the regulatory mechanisms that protect bone?

In a paper published recently in Scientific Reports, researchers from the Forsyth Institute and the Universidad de Chile describe a mechanism that unlocks a piece of the puzzle. Looking at periodontal disease in a mouse model, scientists found that a specific type of T cell, known as regulatory T cells, start behaving in unexpected ways. These cells lose their ability to regulate bone loss and instead begin promoting inflammation.

"That is important because, in many therapies analyzed in in-vivo models, researchers usually check if the number of regulatory T cells has increased. But they should check if these cells are indeed functioning," says Dr. Carla Alvarez, a postdoctoral researcher at Forsyth and lead author of the paper.

Regulatory T cells control the body's immune response. In periodontal disease, bone loss occurs because the body's immune system responds disproportionately to the microbial threat, causing inflammation and destroying healthy tissue. Normally, regulatory T cells help suppress that destruction, but they appear to lose their suppressive abilities during periodontal disease.

In scientific terms, this process is analyzed in the field of osteoimmunology, which explores the complex interactions between the immune system and bone metabolism.

"This is an interesting mechanism highlighting how the bone loss is taking place in periodontal disease," says Dr. Alpdogan Kantarci, Senior Member of Staff at Forsyth and co-author of the paper together with Dr. Rolando Vernal, Professor from the School of Dentistry at Universidad de Chile.

In the case of periodontal disease, a potential therapy targeting regulatory T cells could restore the T cells' normal functioning, not just increase their numbers.

"Unfortunately, this is not a linear process--that's the complicated part," Kantarci says.

Periodontal disease is initiated by microbes in the mouth, making it all the more complex.

"The relationship between immune response and bone is not so straightforward," says Alvarez. "There are multiple components. You have to imagine a complex network of signaling and cells that participate."

This cellular and microbial complexity is what makes the disease so difficult to study in humans. However, examining this mechanism in humans is the next step of the research, Alvarez says. The research team is planning a collaborative study to look at healthy and diseased patients, intending to observe similar mechanisms to what was seen in the animal model.

Tuesday, January 5, 2021

Dental experts discover biological imbalance is the link between gum and kidney disease

An imbalance of the body's oxygen producing free radicals and its antioxidant cells could be the reason why gum disease and chronic kidney disease affect each other, a new study led by the University of Birmingham has found.

Periodontitis - or gum disease - is a common, inflammatory disease which causes bleeding gums, wobbly or drifting teeth and can eventually result in tooth loss.

Previous studies have shown a link between the severe oral inflammation caused by gum disease and chronic kidney disease (CKD) which demonstrated that those with worse inflammation of the gums have worse kidney function.

Previous research also showed that patients with CKD and periodontitis experience a drop in survival rates, similar in magnitude to if they had diabetes instead of gum inflammation, suggesting that gum inflammation may casually affect kidney function.

In this latest study, led by researchers at the University of Birmingham, over 700 patients with chronic kidney disease were examined using detailed oral and full-body examinations including blood samples. The aim was to test the hypothesis that periodontal inflammation and kidney function affect each other and to establish the underlying mechanism that may facilitate this.

Results showed that just a 10% increase in gum inflammation reduces kidney function by 3%. In this group of patients, a 3% worsening in kidney function would translate to an increase in the risk of kidney failure over a 5 year period from 32%-34%. Results also showed that a 10% reduction in kidney function increases periodontal inflammation by 25%.

In contrast to current beliefs that inflammation is the link between periodontitis and other systemic diseases, researchers found for the first time, that in this group of patients, the effect was caused by a biological process called 'oxidative stress' - or, an imbalance between reactive oxygen species and the body's antioxidant capacity which damages tissues on a cellular level.

Lead author Dr Praveen Sharma, from the Periodontal Research Group at the University of Birmingham's School of Dentistry, said: "This is the first paper to quantify the casual effect of periodontitis on kidney function and vice-versa as well as the first to elucidate the pathways involved.

"It showed that even a modest reduction in gum inflammation can benefit renal function. Given the relative ease of achieving a 10% reduction in gum inflammation, through simple measures like correct brushing techniques and cleaning between the teeth, these results are very interesting.

"We hope that this research paves the way for further studies to see if improvements in kidney function, following periodontal care, translate to longer, healthier life for patients with chronic kidney disease. We would also hope that the hypothesis we have identified could be tested in other groups."

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The paper, 'Oxidative stress links periodontal inflammation and renal function', was published in the Journal of Clinical Periodontology.

Gum disease-causing bacteria borrow growth molecules from neighbors to thrive

UNIVERSITY AT BUFFALO

Research News

BUFFALO, N.Y. - The human body is filled with friendly bacteria. However, some of these microorganisms, such as Veillonella parvula, may be too nice. These peaceful bacteria engage in a one-sided relationship with pathogen Porphyromonas gingivalis, helping the germ multiply and cause gum disease, according to a new University at Buffalo-led study.

The research sought to understand how P. gingivalis colonizes the mouth. The pathogen is unable to produce its own growth molecules until it achieves a large population in the oral microbiome (the community of microorganisms that live on and inside the body).

The answer: It borrows growth molecules from V. parvula, a common yet harmless bacteria in the mouth whose growth is not population dependent.

In a healthy mouth, P. gingivalis makes up a miniscule amount of the bacteria in the oral microbiome and cannot replicate. But if dental plaque is allowed to grow unchecked due to poor oral hygiene, V. parvula will multiply and eventually produce enough growth molecules to also spur the reproduction of P. gingivalis.

More than 47% of adults 30 and older have some form of periodontitis (also known as gum disease), according to the Centers for Disease Control and Prevention. Understanding the relationship between P. gingivalis and V. parvula will help researchers create targeted therapies for periodontitis, says Patricia Diaz, DDS, PhD, lead investigator on the study and Professor of Empire Innovation in the UB School of Dental Medicine.

"Having worked with P. gingivalis for nearly two decades, we knew it needed a large population size to grow, but the specific processes that drive this phenomenon were not completely understood," says Diaz, also director of the UB Microbiome Center. "Successfully targeting the accessory pathogen V. parvula should prevent P. gingivalis from expanding within the oral microbial community to pathogenic levels."

The study, which was published on Dec. 28 in the ISME Journal, tested the effects of growth molecules exuded by microorganisms in the mouth on P. gingivalis, including molecules from five species of bacteria that are prevalent in gingivitis, a condition that precedes periodontitis.

Of the bacteria examined, only growth molecules secreted by V. parvula enabled the replication of P. gingivalis, regardless of the strain of either microbe. When V. parvula was removed from the microbiome, growth of P. gingivalis halted. However, the mere presence of any V. parvula was not enough to stimulate P. gingivalis, as the pathogen was only incited by a large population of V. parvula.

Data suggest that the relationship is one-directional as V. parvula received no obvious benefit from sharing its growth molecules, says Diaz.

"P. gingivalis and V. parvula interact at many levels, but the beneficiary is P. gingivalis," says Diaz, noting that V. parvula also produces heme, which is the preferred iron source for P. gingivalis.

"This relationship that allows growth of P. gingivalis was not only confirmed in a preclinical model of periodontitis, but also, in the presence of V. parvula, P. gingivalis could amplify periodontal bone loss, which is the hallmark of the disease," says George Hajishengallis, DDS, PhD, co-investigator on the study and Thomas W. Evans Centennial Professor in the University of Pennsylvania School of Dental Medicine.

"It is not clear whether the growth-promoting cues produced by P. gingivalis and V. parvula are chemically identical," says Diaz. "Far more work is needed to uncover the identity of these molecules."

Dental News Report