THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14



Session will examine how modulating the microbiome can affect rheumatoid arthritis

Curtis Huttenhower, PhD
Curtis Huttenhower, PhD

The microbiome, unlike genetic biomarkers, presents a tremendous opportunity for understanding disease because it’s able to be manipulated once you find the right way, said Curtis Huttenhower, PhD, one of the Modulation of RA Disease Activity Through Dietary Restoration of the Microbiome session presenters; however, there’s still so much unknown about finding the right way to manipulate the microbiome.

The first viewing on this session, on Monday, Nov. 9, from 12 – 1 p.m. EST, will feature a live question-and-answer session. Registered attendees have on-demand access to watch a replay of the session through Wednesday, March 11.

Dr. Huttenhower, professor of computational biology and bioinformatics in the Department of Biostatistics, School of Public Health at Harvard University, and Monica Guma, MD, PhD, an assistant professor of medicine at the University of California-San Diego, will provide an overview on the current understanding of how gut microbial communities contribute to immune development and regulation, and how imbalances in the gut microbiota, termed dysbioses, are present in patients with seropositive rheumatoid arthritis.

“This session gives us an opportunity to see the latest work on predicting progression of disease, response to treatment, and potential therapies, be they direct modulation of the microbiome or indirect factors,” Dr. Huttenhower said. “These can include diet and pharmaceuticals that can improve disease responsiveness by not just directly targeting inflammation, but by also or instead modulating the microbiome.”

The session will highlight a series of studies from the Inflammatory Arthritis Microbiome Consortium (IAMC), a group based at the Oxford University Kennedy Institute of Rheumatology investigating different ways the microbiome contributes to adult and juvenile arthritis onset or progression. These studies include: What changes in the microbiome during arthritis? More longitudinally—does anything about the microbiome at arthritis onset determine its progression or response to treatment? How does that differ between juvenile and adult forms of arthritis? This is of particular interest since the microbiome, also unlike genetics, is quite temporally dependent on different periods of life, Dr. Huttenhower said.

“One of the things I’ve been surprised by working on arthritis and the microbiome, in addition to inflammatory diseases in the gut itself, is that there are unexpected similarities between gut microbial perturbations that arise in arthritis and those in IBD, or to a lesser degree, colorectal cancer,” he said. “We don’t have a great understanding of why, yet. There’s initial epidemiology around shared mechanism of microbes that can either cause or take advantage of immune disruptions, which then manifest either locally in the gut, or in some cases get transmitted systemically by the immune system or biochemical processes to cause joint inflammation.”

Two very actionable ways the microbiome can influence immune health are either by metabolically mediated mechanisms (diet) or chemically mediated mechanisms (pharmaceuticals). A few drug-derived microbial activities are best understood so far since drugs—by definition—have large, rapid chemical effects. There’s less known about making precision modifications to the microbiome over a short- or long-term period with typical diets than with pharmaceuticals, he said.

Current progress will be discussed in the interactions of the gut microbiome with chemicals, including both from diet and pharmaceuticals, to manage disease. In some cases, these can be preventative, by encouraging “anti-inflammatory” microbes; in others, they can facilitate response to treatment after disease onset, testing whether specific microbial configurations are associated with clinical disease activity. The session will also address patient engagement and self-management in regard to diet.

Dr. Huttenhower is thrilled to see the microbiome become more prevalent in rheumatology and is excited for all of the learning opportunities this session presents.

“It’s a convergence of many different fields,” he said. “As a primarily computational biologist, I want to learn more about how this kind of basic science and epidemiology can have an impact on clinical practice and vice versa. Likewise, I hope clinicians can come to have more confidence about the current state of biochemistry, microbiology, and immunology that can ultimately lead to more options for patients.”