Article
Elevated zonulin and calprotectin levels in patients with rheumatoid arthritis indicate subclinical bowel inflammation
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Published: | August 31, 2022 |
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Introduction: The pathophysiology of rheumatoid arthritis (RA) is still poorly understood. Increasingly, research is focusing on the intestine as the largest immunological organ and the “gut-joint-axis”. Microbial dysbiosis as well as a leaky gut and resulting subclinical inflammation as possible trigger mechanisms of arthritis point to the importance of a “healthy” diet for the prevention/treatment of RA.
Methods: In this clinical study, the dietary behaviour of 42 patients with RA (median age 60.5 years, female proportion 62%, median BMI 27.2 kg/m2) and a median disease duration of 3.5 years was analyzed using a dietary protocol for at least 3 days each (PRODI nutrition software). Among other things, the intake of dietary fiber was examined. Zonulin, calprotectin and the short-chain fatty acids butyrate, acetate and propionate were determined in parallel in the stool.
Results: Mean dietary fiber intake was 16.0 gr/d (min. 4.2 g/d – max. 28.7 g/d). Men (15.9 g/d) and women (16.1 g/d) did not differ in dietary fiber intake. Intake of water-soluble dietary fiber that are degradable by symbionts was very low with 5.2 gr/d. Zonulin was significantly elevated at 343.81 ng/g (<61 ng/g) ranging from 45.4 ng/g to 625.4 ng/g. Zonulin levels did not correlate with age, sex and disease activity or therapy. Calprotectin was also elevated with a mean value of 79.65 µg/g (<50 µg/g) (Min. 3.1 µg/g – Max 706 µg/g). Mean values for butyrate, acetate and propionate were 7.8 µmol/g, 35.2 µmol/g and 9.0 µmol/g, respectively, with a considerable spread.
Conclusion: 41/42 patients had significantly elevated fecal zonulin levels. Zonulin increases intestinal permeability by decreasing tight junction proteins and induces T-cell mediated mucosal inflammation. Calprotectin as a marker of intestinal inflammation was also increased in 23/42 patients. Dietary fiber intake of RA patients was significantly below current DGE recommendations (>30g/day). It is postulated that an increase in dietary fiber intake could have positive effects on zonulin and calprotectin by reducing subclinical intestinal inflammation.