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Inflammatory Arthritis Linked to Characteristic Gut Microbial Community Changes

NEW YORK – A team from the US and UK has teased out the microbiome shifts associated with a collection of conditions classified as inflammatory arthritis, including altered representation of microbial genes and pathways involved in metabolic and inflammatory processes.

"The signals we detected associated with this family of systemic inflammatory conditions largely paralleled those identified in diseases defined by gastrointestinal inflammation, such as [inflammatory bowel disease]," senior and corresponding author Curtis Huttenhower, a researcher affiliated with Harvard University, the Broad Institute's infectious disease and microbiome program, and the Harvard T.H. Chan School of Public Health, and his colleagues wrote in Science Translational Medicine on Wednesday.

As part of the Inflammatory Arthritis Microbiome Consortium, the researchers relied on shotgun metagenomic sequencing to profile the gut microbe community in stool samples from 440 individuals between the ages of 20 and 93 years, recruited at UK clinical sites in Oxford, Birmingham, and Newcastle.

The participants included 221 individuals with inflammatory arthritis conditions ranging from rheumatoid arthritis or psoriatic arthritis to ankylosing spondylitis, the team explained, along with 219 unaffected controls.

Based on gut microbial sequences identified, the researchers saw differences across some 2 percent of gut taxonomy in inflammatory arthritis-affected individuals, similar to patterns previously described in distinct inflammatory conditions such as inflammatory bowel disease or type 1 diabetes.

"In patients with inflammatory arthritis, the overall compositional and functional profiles of the gut microbiome were substantially altered," the authors reported. "We identified enrichment of typically oral, proinflammatory, and mucin-degrading microbes, with a corresponding decrease in several typical human gut-resident clades."

When the team dug into the specific microbial shifts in individuals with inflammatory arthritis, it flagged a set of microbes that tracked with rheumatoid arthritis, ankylosing spondylitis, or related symptoms such as anemia, inflammation, or altered levels of a C-reactive protein in the blood.

"Our results confirm and extend previous findings of increased carriage of typically oral and inflammatory taxa and decreased abundance and prevalence of typical gut clades, indicating that distal inflammatory conditions, as well as local conditions, correspond to alterations to the gut microbial composition," the authors explained.

In particular, the team flagged inflammatory arthritis-associated changes to the gut microbiome that are expected to alter processes such as iron sequestration and vitamin B salvage or synthesis, along with other biosynthetic pathway shifts.

Together, the authors noted, "findings of community level taxonomic and functional alterations in the gut microbiome implicate an interplay between host genetics, immune system, and gut microbiome over the course of initiation, progression, and severity of arthritis."

Even so, they advised that "[a]lthough these findings point to pathways and molecules of interest and will serve as an important resource for hypothesis generation, future work will be required to determine if these consistent functional changes occur causally, in response to inflammatory arthritis, or both."

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