The study, which links a species of intestinal bacteria known as Prevotella copri to the onset of rheumatoid arthritis, is the first demonstration in humans that the chronic inflammatory joint diseases such as rheumatoid arthritis may be mediated in part by bacteria that make up the intestinal microbiota.
Writing in the open-access journal eLife, the US-based researchers behind the study said their findings add to the growing evidence that the trillions of microbes in our body play an important role in regulating health.
"Studies in rodent models have clearly shown that the intestinal microbiota contribute significantly to the causation of systemic autoimmune diseases," said Professor Dan Littman of NYU School of Medicine.
"Our own results in mouse studies encouraged us to take a closer look at patients with rheumatoid arthritis, and we found this remarkable and surprising association," he confirmed. "At this stage, however, we cannot conclude that there is a causal link between the abundance of P. copri and the onset of rheumatoid arthritis."
"We are developing new tools that will hopefully allow us to ask if this is indeed the case."
The team used sophisticated DNA analysis to compare gut bacteria from faecal samples of patients with rheumatoid arthritis and healthy individuals - including 16S sequencing on 114 stool samples from rheumatoid arthritis patients and controls, and shotgun sequencing on a subset of 44 such samples.
Littman and his colleagues found that P. copri was more abundant in patients newly diagnosed with rheumatoid arthritis than in healthy individuals or patients with chronic, treated rheumatoid arthritis.
They reported that 75% of stool samples from patients newly diagnosed with rheumatoid arthritis carried P. copri compared to 21.4% of samples from healthy individuals; 11.5% from chronic, treated patients; and 37.5% from patients with psoriatic arthritis.
Moreover, the overgrowth of P. copri was associated with fewer beneficial gut bacteria belonging to the genera Bacteroides.
"Expansion of P. copri in the intestinal microbiota exacerbates colonic inflammation in mouse models and may offer insight into the systemic autoimmune response seen in rheumatoid arthritis," commented Dr Randy Longman, a co-author of the study. Although exactly how this expansion relates to disease remains unclear even in animal models, he said.
Why P. copri growth seems to take off in newly diagnosed patients with rheumatoid arthritis is also unclear, the team said - who noted that the P. copri extracted from stool samples of newly diagnosed patients appears genetically distinct from P. copri found in healthy individuals, thus adding to the mystery.
The team now plan to validate their results in regions beyond New York - since gut flora can vary across geographical regions - and also plan to investigate whether gut flora can be used as a biological marker to guide treatment.
Published online, open access, doi: 10.7554/eLife.01202
" Expansion of intestinalPrevotella copricorrelates with enhanced susceptibility to arthritis"
Authors: Jose U Scher, Andrew Sczesnak, Randy S Longman, et al