Randomized double-blinded controlled trial on the effect of synbiotic supplementation on IL-17/IL-23 pathway and disease activity in patients with axial spondyloarthritis

Abstract

Background

Interleukin 17 (IL17)-expressing CD4⁺ T cells and IL-17/IL-23 pathway play a key role in the pathogenesis of axial spondyloarthritis (axSpA). Synbiotics have been suggested due to their immunomodulatory effects in the treatment of autoimmune diseases. This randomized double-blind, placebo-controlled trial was designed to assess the effects of synbiotic supplement on IL-17/IL-23 pathway and disease activity in patients with axSpA.

Methods

Forty-eight axSpA patients were randomly allocated to use one synbiotic capsule or placebo daily for 12 weeks. Disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and ASAS-endorsed disease activity score-C-reactive protein (ASDAS-CRP). The secondary outcome was proportion of IL17-expressing CD4+ T cells, IL-17 and IL-23 gene expression, and supernatant levels of IL-17 and IL-23, which were measured at the baseline and end of the trial.

Results

A total of 48 patients were randomized into the synbiotic and placebo groups. Thirty-eight patients completed the study. Synbiotic supplementation significantly reduced the proportion of IL17-expressing CD4⁺ T cells (4.88 ± 2.47 vs. 2.16 ± 1.25), gene expression of IL-17 (1.03 ± 0.24 vs. 0.65 ± 0.26) and IL-23 (1.01 ± 0.13 vs. 0.68 ± 0.24) and serum IL-17 (38.22 ± 14.40 vs. 24.38 ± 11.68) and IL-23 (51.77 ± 17.40 vs. 32.16 ± 12.46) compared with baseline. Significant differences between groups were noticed only in the proportion of IL17-expressing CD4⁺ T cells, and IL-17 and IL-23 gene expression. Synbiotic supplementation did not significantly alter BASDAI and ASDAS-CRP compared with baseline and placebo group at the end of trial.

Conclusion

Present study indicated beneficial effect of synbiotic supplement on IL-17/IL-23 pathway without improving disease activity in axSpApatients.

Highlights

• Synbiotic supplementation reduced IL17-expressing CD4⁺ T cells proportion in axSpA.

• Synbiotic supplementation decreased IL-17 and IL-23 gene expression in axSpA.

• Synbiotic supplementation did not change disease activity score in axSpA.

Keywords:

• Synbiotics
• IL-17/IL-23 pathway
• ankylosing spondylitis
• axial spondyloarthritis
• disease activity

Acknowledgements

The findings of this manuscript are derived from the MD (specialty degree in Internal Medicine) dissertation of Dr Masoud Ahangari Maleki documented in Tabriz University of Medical Sciences, Tabriz, Iran. We are thankful to the patients for their cooperation.

Author contributions

MAM, AKH, and AMM participated in study design. MAM and AKH participated in patient selection and data collection. MSS and MY performed molecular and immunological measurements. MSS, AMM, and MY contributed to data analysis. MAM and AMM wrote the article. MAM, AKH, and AMM participated in the final edition of the manuscript. All authors reviewed and approved the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data underlying this article will be shared on reasonable request to the corresponding author.

Additional information

Funding

This work was financially supported by the Connective Tissue Diseases Research Center of Tabriz University of Medical Sciences, Tabriz, Iran (Grant No. 62919).