Patients with gut dysbiosis show worse axial SpA disease activity, physical function
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Gut dysbiosis is more frequent in patients with ankylosing spondylitis, compared with controls, and is associated with worse axial spondyloarthritis disease activity and physical function, according to data.
“The link between spondyloarthritis (SpA) and inflammatory bowel disease (IBD) is well recognized,” Jonas Sagard, of Lund University, in Sweden, and colleagues wrote. “IBD patients are at increased risk of developing SpA, and the reverse is likewise true, with prevalence estimates of diagnosed IBD in axial SpA (axSpA) cohorts between 5% and 10%. IBD is associated with an altered intestinal bacteria composition, a condition known as intestinal or gut dysbiosis.
“Recently, several studies have reported gut dysbiosis also in ankylosing spondylitis (AS), whereas little is known about gut microbiota in non-radiographic axSpA (nr-axSpA) patients,” they added. “Furthermore, previous studies have linked intestinal inflammation, assessed either histologically, or estimated via elevated fecal calprotectin (F-calprotectin) levels, to more active axSpA disease and worse prognosis. Yet, it remains largely unknown whether gut microbiota aberrations alone, independent of intestinal inflammation, is associated with more severe axSpA.”
To compare gut dysbiosis frequency between patients with AS and non-radiographic axial SpA, as well as health controls, and to examine whether it is associated with axial SpA disease activity, physical function, mobility and pain, Sagard and colleagues analyzed patients from the population-based SPARTAKUS cohort. According to the researchers, SPARTAKUS includes patients with axial SpA with at least one outpatient rheumatology visit to Skåne University Hospital, in Sweden, from 2011 to 2014.
For their own analysis, Sagard and colleagues assessed the feces of 44 patients with non-radiographic axial SpA and 88 with AS — all without IBD — as well as from 46 healthy control individuals without IBD or any rheumatic disease. Assessments were performed using 16SrRNA analysis. The researchers graded gut microbiome imbalances on a scale of 1 to 5 using the GA-map Dysbiosis Test, with a grade of 3 or greater denoting dysbiosis.
Sagard and colleagues compared proportions of individuals with gut dysbiosis between the groups. They also compared standard measures of axial SpA disease activity, physical function, mobility and pain between patients with AS or axial SpA, with and without dysbiosis, univariately and adjusted for relevant cofounders.
According to the researchers, 36% of patients with AS demonstrated gut dysbiosis, compared with 17% among healthy controls (P = .023). Meanwhile, the proportion of patients with non-radiographic axial SpA who had gut dysbiosis was 25% — not significantly different from either the AS or control groups, they wrote.
In the univariate analysis, most axial SpA measures were significantly worse among patients with gut dysbiosis, compared with those without. Between group differences were 0.6 (95% CI, 0.2-0.9) for ASDAS-CRP; 1.6 (95% CI, 0.8-2.4) for BASDAI; 0.3 (95% CI, 0.1-0.5) for evaluator’s global disease activity assessment, using a Likert scale of 0 to 4; 1.5 (95% CI, 0.6-2.4) for BASFI; and 1.3 (95% CI, 0.4-2.2) for VAS pain.
Differences remained significant after adjusting for demographics, lifestyle factors, treatment, gut inflammation and gut symptoms, save for VAS pain. Neither BASMI nor C-reactive protein were associated with gut dysbiosis.
“In the overall axSpA group (nr-axSpA and AS combined), the presence of gut dysbiosis was independently associated with worse disease activity and physical function, seemingly irrespective of both gut inflammation and ongoing treatments,” Sagard and colleagues wrote. “Further research is needed to assess the validity of these findings also in other axSpA cohorts, as well as to gain a deeper understanding of the connection between gut microbiota and axSpA, and examine whether a causal relationship exists.
“This would offer guidance as to whether targeting the intestine therapeutically, with regard to the luminal microbiota composition and/or mucosal inflammation, could be a relevant approach to try to interfere with axSpA development or mitigate the disease course,” they added. “Nonetheless, the current results add to the steadily growing body of evidence for an important, potentially pathobiological, link between disturbances in gastrointestinal homeostasis and axSpA.”
Perspective
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It has been a few decades since the recognition of the tantalizing link between Ankylosing Spondylitis — and in fact between the entire seronegative spondyloarthropathy group of disorders — and enterocolitis-like gut inflammation, which at times may be occult or minimally symptomatic. Sagard, Oloffson, Wallman et al., in their article “Gut dysbiosis associated with worse disease activity and physical function in axial spondyloarthritis,” confirm and further advance the concept, analyzing the microbiome in AS and non-radiographic axial SpA, and its relationship to disease characteristics.
Their method mines the Swedish SPARTAKUS population cohort, with patients hailing from southern Sweden, enrolling consecutive axial spondyloarthropathy patients, both non-radiographic and AS, and adding a control group. From these, they collected fecal and serum samples, and performed imaging and metrics to compare the degree of dysbiosis with a broad group of disease activity measures.
The authors’ findings include a positive association between a higher degree of dysbiosis and AS disease activity, which is also present in the non-radiographic axial Spa group, albeit not to a statistically significant degree. Oddly those with higher dysbiosis were less frequently HLA B27 positive. In all patients with axial SpA, greater dysbiosis correlated with worse ASDAS-CRP and BASDAI scores, MDGlobal and VAS pain scores — findings at the leading edge of this research effort. Yet much remains to be elucidated regarding specific compositions of patients’ bacterial flora and the implications for pathogenesis, immunologic aberrations, and clinical features.
Acknowledged weaknesses were minor, notably the cohort lacking some diversity and generalizability, and the absence of data on pre- and probiotic OTC use, a widespread phenomenon. Additionally, one has the suspicion that potential therapeutic designs stemming from microbiome investigations may be further down the road.
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David A. McLain, MD, MACR, FACP, FRCP
Dysbiosis is associated with many diseases, including irritable bowel syndrome, inflammatory bowel diseases, obesity and diabetes. Sagard, et al., have shown that the degree of dysbiosis is associated with worse disease activity in axial spondyloarthritis.
The diversity of the human microbiome was first observed by Antonie van Leewenhoek, a Dutch merchant. He noted a striking difference between microbes found in samples taken from the mouth vs. those in the feces in the early 1680s. It was not until the 19th century that Pasteur and Koch studied microbes and related them to disease.
Trillions of symbiotic microbial organisms live in and on the human body, and with the advent of DNA probes, they can be found throughout, including the oral, gastrointestinal, respiratory, urinary and vaginal tracts, as well as the nose, brain, ear, skin and bloodstream. Their genes are now thought to contribute more to human survival than the genes of the human. There is more bacterial DNA in the human body than human DNA (360:1).
Such genes, the human microbiome, are, for example, pivotal to digestion, aging, the immune system, the modulation of the central nervous system, mood and cognitive ability. This makes the human microbiome an essential organ in the human body. Without it, the human body cannot function. A novel dysbiosis test of fecal samples was developed and tested by Casén, et al., in 2015. The human microbiome and dysbiosis is a fascinating area of research and it is satisfying to see progress being made in this important area.
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