Microbiome Changes Linked to Childhood Spondyloarthritis

To the increasing hints that disturbances in the human-bacterial ecosystem may be at the root of rheumatic disease, add this: Children with spondyloarthritis (SpA) have the same low levels of a microbe called Faecalibacterium prausnitzii that occur in children with inflammatory bowel disease.

This brings a microbiome connection to two autoimmune disorders that also have "strong clinical and pathological links," observed Matthew Stoll MD, an assistant professor of rheumatology in the division of pediatric rheumatology at the University of Alabama-Birmingham. At the ACR pediatric rheumatology meeting in Orlando, Stoll described studies that used DNA sequening to characterize all species of enteric bacteria in 28 children with enthesitis-related arthritis and 13 controls who were either healthy or had non-inflammatory joint pain.

Levels of Faecalibacterium were significantly lower in the children with SpA than in controls. (Some subsets of SpA patients also had non-significantly higher levels of Bacterioides.)

F. prausnitzii  appears to have anti-inflammatory effects, Stoll told Rheumatology Network, although "it is not known yet exactly what the effect is." A next step will to be repeat the studies in a larger cohort of patients with other subtypes of juvenile arthritis.

"The number of diseases associated with changes in microbial diversity continues to grow by the day," said microbiologist David Artis PhD of the University of Pennsylvania Perelman School of Medicine at a separate session on the microbiome.

In germ-free mice, he added, it appears that permanent shifts in microbiota after antibiotic treatment can influence the development of the immune system, and influence pro-inflammatory or regulatory immune responses. He mentioned a study by Daniel Littman of the New York University School of Medicine and coworkers showing that a single species of bacterium introduced into the gut of germ-free mice could drive the development of autoimmune arthritis. A widely cited paper by the same team, published last November, linked the presence of the gut bacterium Prevotella copri to susceptibility to arthritis.

"This organism is difficult to work with and culture," said Artis, "so there has been no followup to date. But certainly the associations in this paper were very strong."

Growing attention to the "barrier cells" in skin and mucosa has revealed a unique set of innate immune cells that are neither T nor B cells, are not myeloid or granulocytic, and have no receptors for pathogens, but are increased in inflammatory conditions, he added. Apparently important regulators of barrier function, they are the only cells to express receptors for interleukin-22.

"We're just beginning to understand the role of these cells in innate immunity and infection," Artis said. The "real challenge," he added, is to identify the ligands responsible for these newfound immune phenomena, and to identify small molecules to control them.