Does Gum Disease Indicate Future Joint Problems?

Bacteria Responsible for Gum Disease Facilitates Rheumatoid Arthritis

Does gum disease indicate future joint problems? Although researchers and clinicians have long known about an association between two prevalent chronic inflammatory diseases -- periodontal disease and rheumatoid arthritis (RA) -- the microbiological mechanisms have remained unclear.

In an article published in PLoS Pathogens, University of Louisville School of Dentistry Oral Health and Systemic Diseases group researcher Jan Potempa, PhD, DSc, and an international team of scientists from the European Union's Gums and Joints project have uncovered how the bacterium responsible for periodontal disease, Porphyromonas gingivalisworsens RA by leading to earlier onset, faster progression and greater severity of the disease, including increased bone and cartilage destruction.

The scientists found that P. gingivalis produces a unique enzyme, peptidylarginine deiminanse (PAD) which then enhances collagen-induced arthritis (CIA), a form of arthritis similar to RA produced in the lab. PAD changes residues of certain proteins into citrulline, and the body recognizes citullinated proteins as intruders, leading to an immune attack. In RA patients, the subsequent result is chronic inflammation responsible for bone and cartilage destruction within the joints.

Potempa and his team studied another oral bacterium, Prevotella intermedia for the same affect, but learned it did not produce PAD, and did not affect CIA. 

“Taken together, our results suggest that bacterial PAD may constitute the mechanistic link between P. gingivalis periodontal infection and rheumatoid arthritis, but this ground-breaking conclusion will need to be verified with further research," he said.  Potempa said he is hopeful these findings will shed new light on the treatment and prevention of RA.”

Studies indicate that compared to the general population, people with periodontal disease have an increased prevalence of RA and, periodontal disease is at least two times more prevalent in RA patients. Other research has shown that a P. gingivalis infection in the mouth will precede RA, and the bacterium is the likely culprit for onset and continuation of the autoimmune inflammatory responses that occur in the disease.

sciencedaily.com

Healthy Diet Discourages Obesity Microbes in Gut

When you dine, you are never alone. Trillions of microbial guests, resident in your gut, eat with you. They help digest your food and convert it into energy and fat. Now, new research suggests changing the mix of gut microbes can prevent obesity, but only if combined with a healthy diet.

This was the conclusion of a study from researchers at Washington University School of Medicine in St. Louis, as reported in the journal Science on September 6th, 2013. The study reveals another clue about the intimate ties between gut bacteria and diet in the development of obesity.

'Lean' gut microbes and healthy diet

The researchers bred mice in a sterile environment so they had no gut microbes of their own. Then, they took gut microbes from human twins - where one twin was lean and the other obese - and transplanted them to the mice. Mice receiving the obesity-related gut microbes gained weight and fat, and developed obesity-related metabolic problems, while the mice that received the leanness-related gut microbes did not. Researchers then paired up the mice so that the ones with microbes from the lean human twin were put in the same cages as mice with gut microbes from the obese twin. Mice naturally eat each other's feces, so the researchers wondered if they would transfer gut microbes to each other, and if so, which set would end up dominating the gut: the leanness ones or the obesity ones?

The study suggests that eating a diet high in fruits and vegetables encourages leanness-related microbes to populate the gut, leading to better weight control.

They found the answer depended on the type of diet.

If the mice were on a healthy diet - one low in saturated fat and high in fruits and vegetables - then the leanness-associated microbes invaded the gut of the mice with the obesity-associated microbes, stopping them putting on weight and developing metabolic problems tied to insulin resistance.

In humans, significant weight gain can be linked to insulin resistance, which is the first sign of metabolic disorder that can lead to type 2 diabetes.

Senior author Professor Jeffrey I. Gordon, director of the Center for Genome Sciences & Systems Biology at Washington University, says:

"Eating a healthy diet encourages microbes associated with leanness to quickly become incorporated into the gut. But a diet high in saturated fat and low in fruits and vegetables thwarts the invasion of microbes associated with leanness."

He adds that the finding is important for the development of next-generation probiotics as a treatment for obesity.

Ties between gut microbe mix, diet and obesity

Prof. Gordon has been working on the link between gut microbes and obesity for a while. In 2006, he and his team reported two studies that found gut microbes influence how much energy is extracted from food and stored as fat.  They found the clue lies in the relative abundance of two major families of intestinal bacteria: Firmicutes and Bacteroidetes. In this latest study, they found weight gain, accumulation of fat and development of metabolic symptoms were prevented in mice carrying the obesity-related gut microbes when they followed the healthy diet. This is because their guts were invaded by Bacteroidetes bacteria from the mice carrying the leanness-related gut microbes. Bacteroidetes are efficient at harvesting calories and nutrients from food. In 2009, the team reported how a westernized diet leads to obesity via gut microbes. In that study, they transplanted human gut microbes into germ-free mice, then switched their diet from a low-fat plant-based one to a more westernized diet high in fat and sugars.  Within one day, obesity-associated microbes were thriving in the animals' guts, and the animals eventually became obese.

This latest study adds another clue to that finding: not only does following a westernized diet seem to encourage gut colonization by more obesity-related microbes, but it also appears to discourage colonization of microbes associated with leanness, leading to weight gain and development of metabolic problems.

Gut microbe mix in obese people is less diverse

The new study also confirms another finding from previous work: the mix of microbes in the guts of obese people is not as diverse as that of lean people, as Gordon explains:

"We think the lack of diversity leaves open niches - or jobs, if you will - that can be filled by microbes associated with leanness. Our results underscore the strong interactions between gut microbes and diet and help illustrate how unhealthy diets select against gut microbes associated with leanness."

Also, throughout the experiments in the new study, Gordon and colleagues found the results did not depend on whether the donor's gut microbes were first grown in the lab or came from a fecal sample: they still transmitted the body composition and metabolic characteristics of the donor.

This is good news for treatment developers: it should be easier to grow the human gut microbes in the lab (and presumably will make for a more palatable message to patients and consumers) than to keep harvesting them from feces samples.

medicalnewstoday.com