Microbiome’s Role in Osteoarthritis

By Linda Rath | Dec. 7, 2023

Osteoarthritis (OA) was for decades mistakenly considered a wear-and-tear disease in which cartilage gradually broke down as a result of a lifetime of use. It’s now known that chronic, low-grade, systemic inflammation as well as inflammation of the synovium and other parts of the joint are responsible for much of the development, progression and pain of OA.

At the American College of Rheumatology’s annual conference in November 2023, Liubov Arbeeva, a biostatistician with the Thurston Arthritis Research Center at the University of North Carolina, and Matlock Jeffries, MD, director of the Arthritis Research Center at the University of Oklahoma, discussed the latest findings about the microbiome and OA.

Aging and obesity are considered the most significant risk factors for OA, although previous injuries also set the stage for it. Excess fat is a particular problem, not only because the weight puts extra pressure on joints, but it also is an active tissue that releases inflammatory proteins that settle in synovial fluid, damaging cartilage, even in non-weight bearing joints. Evidence also increasingly shows that one of the main drivers of inflammation in OA and most other chronic diseases is an off-kilter microbiome.

The basics

The microbiome is made up of trillions of mostly beneficial viruses, bacteria and fungi that live on and in your body. Just about every square inch has its own microbiome, but the gut microbiome is by far the largest and most important. In the last few decades, researchers have learned that these vast colonies of microorganisms have tremendous influence on physical and mental health. Reductions or an imbalance in the number and types of microbes, called dysbiosis, have been linked to many chronic diseases, including heart disease, diabetes, autoimmune conditions, including rheumatoid arthritis and lupus, and brain diseases like Alzheimer’s and Parkinson’s.

How dysbiosis triggers inflammation

A single layer of cells tightly interlocked with proteins acts as a gatekeeper between your gut and the rest of your body. This intestinal barrier allows water and nutrients in, while keeping harmful bacteria and toxins out. The barrier’s health is maintained by the microbiome, so even small alterations in its composition can cause the membrane to become more permeable, or “leaky.” You may have heard the term “leaky gut.” This occurs when endotoxins that should stay in the gut escape into the bloodstream. Your immune system sees them as foreign invaders and goes on the attack, causing body-wide inflammation as well as localized inflammation in some organs and joints.

Arbeeva points to one of the largest studies on the composition of the gut microbiome in people with OA. The researchers, who studied more than 1,400 overweight OA patients, found the microbiome played a “direct role” in OA knee pain and inflammation. The cause was an overabundance of a gut microbial species called Streptococcus. They were able to replicate these results in another large study, and like other experts, they suggest that modifying the microbiome might be key to preventing and treating OA.

Changing the microbiome

Some things that shape the gut microbiome can’t be changed, like your age and the way you were born or fed as an infant, Arbeeva points out. Babies pick up their first dose of healthy microorganisms in the birth canal, and breastmilk contains bacteria that help support growth and immunity. Although you can’t change your early life, you can control things that alter the microbiome for the worse as an adult, especially antibiotics and poor diet.

Antibiotics, which are ubiquitous in Western medicine, immediately alter the microbiome, reducing or eliminating many types of beneficial microbes and allowing pathogenic bacteria to take hold.

The typical American diet also causes big shifts in the microbiome. It’s often low in fiber from fruits and vegetables and high in sugar and saturated fat, which contribute to obesity and a breakdown of the gut barrier. Obesity alone is associated with a loss of beneficial gut bacteria, Arbeeva says, especially Lactobacillus and Bifidobacterium, and with an increase in pro-inflammatory species like Streptococcus that migrate into the joint lining.

Studies have shown that a diet high in fiber tamps down OA-related inflammation and may help rebuild the gut lining. Short-chain fatty acids are produced when beneficial bacteria break down fiber in the colon and are essential for mental and physical health. “People who have OA are low on fiber and short-chain fatty acids,” Arbeeva says. “Eating more fiber can help.”

Tracking bacterial DNA

Dr. Jeffries is on the leading edge of microbiome research. His lab studies obesity, aging and the microbiome — the main contributors to OA. Many key findings have emerged from his research, including:

• Bacterial DNA is found in different parts of the joint, including the cartilage, joint lining (synovium) and synovial fluid. These microbial signatures change as OA develops.
• The microbial DNA makeup of healthy human knee and hip cartilage differs significantly from OA cartilage. In a first-of-its-kind study, Dr. Matlock showed that healthy cartilage contained mainly Firmicutes, common and beneficial bacteria normally found in the gut. OA cartilage was populated by Actinobacteria and Proteobacteria, which also are common in the gut but in large numbers are associated with disease. The microbial populations in OA cartilage were less diverse than in healthy cartilage and hip OA cartilage was less diverse than OA knee cartilage. Dr. Matlock noted they are finding “more and more differences between knee and hip OA.”
• The microbiomes of OA-resistant mice closely resemble those of healthy humans, while the microbiomes of OA-susceptible mice resemble those of people with arthritis.
• Healthy mice who receive a microbiome transplant from OA mice develop arthritis, while a transplant from healthy mice into those with OA can reverse the disease.
• OA bacterial DNA is five times more inflammatory than healthy microbial DNA.
• As other research has shown, Lactobacillus bacteria are strongly resistant to OA and are reduced in OA patients.

Dr. Jeffries says his research underscores the role of the microbiome in inflammatory diseases, but that the microbiome is modifiable.

“If patients change their diet in certain ways, it certainly has an effect on the gut microbiome, and may also change microbial signatures in other locations like joints,” he says. “Cases of OA have been skyrocketing. Our genes haven’t changed, so we have to look at environmental factors [like poor diet and obesity].”