Patients with spondyloarthritis (SpA) have increased intestinal permeability, regardless of their use of nonsteroidal anti-inflammatory drugs (NSAIDs), according to findings from a systematic review published in Seminars in Arthritis and Rheumatism. However, study data were inconclusive regarding intestinal permeability in patients with rheumatoid arthritis (RA).

Researchers of the analysis reviewed the Medline, Embase, and Cochrane Library databases for studies published between 1980 and 2020 that assessed intestinal permeability in patients with SpA and/or RA. From the studies, the researchers extracted the data including year of publication; inclusion criteria; cohort size; mean patient age; classification criteria for SpA and RA; methods used to measure intestinal permeability; disease activity; and use of NSAIDs. The Newcastle Ottawa quality assessment Scale was used to evaluate study quality and risk for bias.

Of 1791 reviewed studies, 23 were included in the final analysis. Sample size ranged from 6 to 206 patients; average patient age ranged from 36 to 52 years. A total of 10 studies examined the effect of NSAIDs on intestinal permeability. The most frequently used methods to measure intestinal permeability were the lactulose/mannitol, 51Cr-ethylenediamine tetra-acetic acid (EDTA) and polyethylene glycols (PEG) 400 tests. Two studies assessed permeability by measuring the concentration of circulating zonulin.

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Of the 23 studies, 12 evaluated permeability in SpA only, 11 in RA only, and 3 in both SpA and RA. Among patients with SpA, increased intestinal permeability independent of testing method was reported in 9 studies. In half of the studies which enrolled patients with RA, no significant correlation between disease status and intestinal permeability was observed. Findings from 3 studies indicated increased permeability in patients with RA compared with healthy control participants; 1 study found increased permeability among patients with active RA only. Regarding disease activity, no studies indicated that increased disease activity in SpA was associated with increased intestinal permeability. However, 2 studies suggested that patients with active RA may have increased permeability compared with those without active RA.

Of the 10 studies reporting NSAID use, few specified medication type or dose; the most common regimens involved indomethacin, naproxen and acetylsalicylic acid. In 2 studies of patients with ankylosing spondylitis (AS), increased permeability was observed after NSAID administration. However, in 2 other studies, NSAIDs were not observed to affect permeability in AS. In studies of patients with RA, NSAIDs were frequently associated with increased permeability. In a study, which reported environmental or genetic factors, fasting was found to reduce intestinal permeability and decrease disease activity in patients with RA. In another study, relatives of patients with SpA were found to have increased permeability compared with nonrelatives. However, data regarding other genetic and/or environmental factors were limited.

Data from the literature indicated that patients with SpA may experience increased intestinal permeability regardless of NSAID use. Data regarding intestinal permeability in RA were less conclusive. Further study is necessary to better assess the relationship between intestinal permeability and rheumatic disease.

“[Further research] might help to determine whether intestinal permeability is a new biomarker and/or new target for inflammatory chronic rheumatisms,” the researchers wrote.


Hecquet S, Totoson P, Martin H, et al. Intestinal permeability in spondyloarthritis and rheumatoid arthritis: a systematic review of the literature. Semin Arthritis Rheum. Published online May 6, 2021. doi:10.1016/j.semarthrit.2021.04.015