Regulatory T Cells in Bioactive Peptides-Induced Oral Tolerance; a Two-Edged Sword Related to the Risk of Chronic Diseases: A Systematic Review

Abstract

This systematic review assesses the literature regarding beneficial and potential detrimental effects of bioactive peptides (BPs), focusing on evidence of regulatory T cells (T-regs) mediated oral tolerance (OT), collagen hydrolysate (CH) supplementation in osteoarthritis (OA) and the association of T-regs with chronic disease. The systematic search was done for articles published from inception to April 2019 using the PubMed and Scopus databases. About 3081 papers were identified by three different search strategies and screened against inclusion criteria which resulted in the inclusion of 22 articles. From the included articles, 12 papers were related to treatment of different disease in vivo by oral administration of BPs, six articles evaluated the effects of CH supplementation, as a rich source of BPs, on OA pain-relief and four observational studies assessed the association of circulating T-regs and risk of cancer and cardiovascular disease (CVD). The evidence obtained from first search strategy, indicated that oral administration of BPs improve clinical manifestations of animal models of allergy, arthritis, atherosclerosis, ulcerative colitis and allograft rejection by T-regs expansion; while, observational studies showed that although higher levels of circulating T-regs reduced risk of CVD and allergy, but, increased risk of solid cancers.

Acknowledgments

We would like to thank Shahid Beheshti University of Medical Sciences.

Disclosure Statement

The authors declare that they have no conflicts of interest.

Author Contribution

M.B. developed the main idea. M.B., A.F., and S.H.D developed the study protocol. M.B. performed the literature search. M.B. and A.F. searched the information sources and screened the identified literature for inclusion criteria, and disagreements were resolved by M.J., H.N, M.E., A.J.M, and S.H.D, M.B., and A.F., prepared the draft of the paper. S.H.D, M.J., H.N, M.E., and A.J.M, contributed to the critical revision of the manuscript. M.B., A.F., M.J., H.N, M.E., A.J.M, and S.H.D, approved the final version.