The Effect of Probiotic Yogurt on Immune System in Systemic Lupus Erythematosus- A Triple-blind, Randomized and Controlled trial
محورهای موضوعی :
راضیه بنکی
1
,
Tahereh Faezi
2
,
Ahmad Esmaeilzadeh
3
,
Mahdi Mahmoudi
4
,
Elham farhadi
5
,
Majid Alikhani
6
1 - Department of Food Science and Technology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
2 - Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
3 - . Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences
4 - Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
5 - Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
6 - Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
کلید واژه: Autoantibodies, Interferon Alfa, Inflammatory factors, Probiotic, Systemic lupus erythematosus,
چکیده مقاله :
Objective:
Systemic lupus erythematosus (SLE) is an autoimmune multisystem disease. The pathogenesis of SLE is multifactorial, and gut microbiota is one of the important factors in SLE pathogenesis. This research aims to evaluate the impact of probiotic yogurt on autoantibodies, inflammatory markers, and cytokines in SLE patients.
Methods:
In this three-blind, randomized controlled trial, thirty-three lupus patients were divided into two groups. The case group received 200 g of probiotic yogurt, and the control group was given 200 g of simple yogurt for 13 weeks. The patients had SLEDAI ≤6 and were on a stable dose of immunosuppressant in the last 3 months, Demography measurements, Blood sampling, and biochemical measurements were analyzed before and after the intervention.
Results:
The level of autoantibodies such as anti-dsDNA did not change significantly by probiotic yogurt (P=0.733), while anti-SSA increased significantly in the control group (P=0.046). The level of ESR decreased in the cases group (P=0.067), while it increased in the control group (P=0.833), but the difference was not significant. About the effect of probiotic yogurt on IFNα as the main cytokine in SLE, it decreased in the cases group (P=0.809) while it increased in the control group (P=0.067), but the difference was not significant. The probiotic and placebo groups at the baseline demographic and clinical features did not differ significantly.
Conclusions: Probiotic yogurt consumption in SLE patients led to a decrease in IFNα and ESR non-significantly.
This study was registered in the Iranian Registry of Clinical Trials (ID: IRCT20240821062833N1).
Objective:
Systemic lupus erythematosus (SLE) is an autoimmune multisystem disease. The pathogenesis of SLE is multifactorial, and gut microbiota is one of the important factors in SLE pathogenesis. This research aims to evaluate the impact of probiotic yogurt on autoantibodies, inflammatory markers, and cytokines in SLE patients.
Methods:
In this three-blind, randomized controlled trial, thirty-three lupus patients were divided into two groups. The case group received 200 g of probiotic yogurt, and the control group was given 200 g of simple yogurt for 13 weeks. The patients had SLEDAI ≤6 and were on a stable dose of immunosuppressant in the last 3 months, Demography measurements, Blood sampling, and biochemical measurements were analyzed before and after the intervention.
Results:
The level of autoantibodies such as anti-dsDNA did not change significantly by probiotic yogurt (P=0.733), while anti-SSA increased significantly in the control group (P=0.046). The level of ESR decreased in the cases group (P=0.067), while it increased in the control group (P=0.833), but the difference was not significant. About the effect of probiotic yogurt on IFNα as the main cytokine in SLE, it decreased in the cases group (P=0.809) while it increased in the control group (P=0.067), but the difference was not significant. The probiotic and placebo groups at the baseline demographic and clinical features did not differ significantly.
Conclusions: Probiotic yogurt consumption in SLE patients led to a decrease in IFNα and ESR non-significantly.
This study was registered in the Iranian Registry of Clinical Trials (ID: IRCT20240821062833N1).
1. Rönnblom L, Alm GV. An etiopathogenic role for the type I IFN system in SLE. Trends Immunol. 2001;22(8):427-31.
2. Fitzgerald-Bocarsly P, Dai J, Singh SJC, reviews gf. Plasmacytoid dendritic cells and type I IFN: 50 years of convergent history. 2008;19(1):3-19.
3. Bengtsson A, Sturfelt G, Truedsson L, Blomberg J, Alm G, Vallin H, et al. Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies. 2000;9(9):664-71.
4. Maidhof W, Hilas OJP, Therapeutics. Lupus: an overview of the disease and management options. 2012;37(4):240.
5. Gladman DD, Urowitz MB, Rahman P, Ibañez D, Tam L-SJTJor. Accrual of organ damage over time in patients with systemic lupus erythematosus. 2003;30(9):1955-9.
6. Alduraibi FK. Distinct Clinical Manifestations Associated with Autoantibodies and Cytokines in Systemic Lupus Erythematosus: The University of Alabama at Birmingham; 2022.
7. Guo X, Yang X, Li Q, Shen X, Zhong H, Yang YJFiP. The microbiota in systemic lupus erythematosus: an update on the potential function of probiotics. 2021;12:759095.
8. Yung S, Chan TMJFii. Mechanisms of kidney injury in lupus nephritis–the role of anti-dsDNA antibodies. 2015;6:475.
9. Yung S, Cheung KF, Zhang Q, Chan TMJJoIR. Mediators of inflammation and their effect on resident renal cells: implications in lupus nephritis. 2013;2013.
10. Sontheimer R, McCauliffe D, Zappi E, Targoff IJAid. Antinuclear antibodies: clinical correlations and biologic significance. 1992;7:3-52; discussion 3.
11. Logar D, Kveder T, Rozman B, Dobovisek JJAotrd. Possible association between anti-Ro antibodies and myocarditis or cardiac conduction defects in adults with systemic lupus erythematosus. 1990;49(8):627-9.
12. Crispín JC, Liossis S-NC, Kis-Toth K, Lieberman LA, Kyttaris VC, Juang Y-T, et al. Pathogenesis of human systemic lupus erythematosus: recent advances. 2010;16(2):47-57.
13. Crispín JC, Tsokos GCJBRI. IL-17 in systemic lupus erythematosus. 2010;2010.
14. Katz-Agranov N, Zandman-Goddard GJIr. The microbiome and systemic lupus erythematosus. 2017;65:432-7.
15. Tomasello G, Mazzola M, Leone A, Sinagra E, Zummo G, Farina F, et al. Nutrition, oxidative stress and intestinal dysbiosis: Influence of diet on gut microbiota in inflammatory bowel diseases. 2016;160(4):461-6.
16. Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet–induced obesity and diabetes in mice. Diabetes. 2008;57(6):1470-81.
17. Abbasi B, Ghiasvand R, Mirlohi M. Kidney function improvement by soy milk containing Lactobacillus plantarum A7 in type 2 diabetic patients with nephropathy: a double-blinded randomized controlled trial. Iranian journal of kidney diseases. 2017;11(1):36.
18. Abbasi B, Mirlohi M, Daniali M, Ghiasvand R. Effects of probiotic soy milk on lipid panel in type 2 diabetic patients with nephropathy: a double-blind randomized clinical trial. Prog Nutr. 2018;20(Suppl 2):70-8.
19. Reardon SJN. Microbiome therapy gains market traction. 2014;509(7500):269-70.
20. Bungau SG, Behl T, Singh A, Sehgal A, Singh S, Chigurupati S, et al. Targeting probiotics in rheumatoid arthritis. 2021;13(10):3376.
21. Esmaeili SA, Mahmoudi M, Momtazi AA, Sahebkar A, Doulabi H, Rastin MJJocp. Tolerogenic probiotics: potential immunoregulators in systemic lupus erythematosus. 2017;232(8):1994-2007.
22. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. 2011;108(38):16050-5.
23. Mu Q, Zhang H, Liao X, Lin K, Liu H, Edwards MR, et al. Control of lupus nephritis by changes of gut microbiota. 2017;5(1):1-12.
24. Guo X, Yang X, Li Q, Shen X, Zhong H, Yang Y. The Microbiota in Systemic Lupus Erythematosus: An Update on the Potential Function of Probiotics. Front Pharmacol. 2021;12:759095.
25 Asoudeh F, Djafarian K, Akhalghi M, Mahmoudi M, Jamshidi AR, Farhadi E, et al. The effect of probiotic cheese consumption on inflammatory and anti-inflammatory markers, disease severity, and symptoms in patients with rheumatoid arthritis: Study protocol for a randomized, double-blind, placebo-controlled trial. 2022;23(1):180.
26. Wahadat MJ, Qi H, van Helden-Meeuwsen CG, Huijser E, van den Berg L, van Dijk-Hummelman A, et al. Serum IFNα2 levels are associated with disease activity and outperform IFN-I gene signature in a longitudinal childhood-onset SLE cohort. Rheumatology (Oxford). 2023;62(8):2872-9.
27. Conti F, Ceccarelli F, Perricone C, Massaro L, Marocchi E, Miranda F, et al. Systemic Lupus Erythematosus with and without Anti-dsDNA Antibodies: Analysis from a Large Monocentric Cohort. Mediators Inflamm. 2015;2015:328078.
28. Littlejohn E, Marder W, Lewis E, Francis S, Jackish J, McCune WJ, et al. The ratio of erythrocyte sedimentation rate to C-reactive protein is useful in distinguishing infection from flare in systemic lupus erythematosus patients presenting with fever. Lupus. 2018;27(7):1123-9.
29. Mu Q, Zhang H, Luo XMJFii. SLE: another autoimmune disorder influenced by microbes and diet? 2015;6:608.
30. Neuman H, Koren OJCOiR. The gut microbiota: a possible factor influencing systemic lupus erythematosus. 2017;29(4):374-7.
31. Forbes JD, Van Domselaar G, Bernstein CNJFim. The gut microbiota in immune-mediated inflammatory diseases. 2016;7:1081.
32. Yao K, Xie Y, Wang J, Lin Y, Chen X, Zhou T. Gut microbiota: a newly identified environmental factor in systemic lupus erythematosus. Frontiers in Immunology. 2023;14.
33. Yu C-F, Peng W-M, Schlee M, Barchet W, Eis-Hübinger AM, Kolanus W, et al. SOCS1 and SOCS3 target IRF7 degradation to suppress TLR7-mediated type I IFN production of human plasmacytoid dendritic cells. 2018;200(12):4024-35.
34. Zegarra-Ruiz DF, El Beidaq A, Iñiguez AJ, Di Ricco ML, Vieira SM, Ruff WE, et al. A diet-sensitive commensal Lactobacillus strain mediates TLR7-dependent systemic autoimmunity. 2019;25(1):113-27. e6.
35. Crow MKJTJoI. Type I interferon in the pathogenesis of lupus. 2014;192(12):5459-68.
36. So JS, Lee CG, Kwon HK, Yi HJ, Chae CS, Park JA, et al. Lactobacillus casei potentiates induction of oral tolerance in experimental arthritis. Mol Immunol. 2008;46(1):172-80.
37. Kemp MGJJoCD. Crosstalk between apoptosis and autophagy: environmental genotoxins, infection, and innate immunity. 2017;10:1179670716685085.
38. Schaupp L, Muth S, Rogell L, Kofoed-Branzk M, Melchior F, Lienenklaus S, et al. Microbiota-induced type I interferons instruct a poised basal state of dendritic cells. 2020;181(5):1080-96. e19.
39. Manfredo Vieira S, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Khan N, et al. Translocation of a gut pathobiont drives autoimmunity in mice and humans. 2018;359(6380):1156-61.
40. Capolunghi F, Rosado MM, Cascioli S, Girolami E, Bordasco S, Vivarelli M, et al. Pharmacological inhibition of TLR9 activation blocks autoantibody production in human B cells from SLE patients. 2010;49(12):2281-9.
41. de Oliveira GLV, Leite AZ, Higuchi BS, Gonzaga MI, Mariano VSJI. Intestinal dysbiosis and probiotic applications in autoimmune diseases. 2017;152(1):1-12.
42. Vieira SM, Pagovich OE, Kriegel MAJL. Diet, microbiota and autoimmune diseases. 2014;23(6):518-26.
43. Cavallo T, Granholm NJTAjop. Bacterial lipopolysaccharide transforms mesangial into proliferative lupus nephritis without interfering with processing of pathogenic immune complexes in NZB/W mice. 1990;137(4):971.
44. Granholm N, Cavallo TJL. Long-lasting effects of bacterial lipopolysaccharide promote progression of lupus nephritis in NZB/W mice. 1994;3(6):507-14.
45. Apperloo-Renkema H, Bootsma H, Mulder B, Kallenberg C, Van Der Waaij DJE, Infection. Host–microflora interaction in systemic lupus erythematosus (SLE): colonization resistance of the indigenous bacteria of the intestinal tract. 1994;112(2):367-73.
46. de la Visitación N, Robles-Vera I, Toral M, O'Valle F, Moleon J, Gómez-Guzmán M, et al. Lactobacillus fermentum CECT5716 prevents renal damage in the NZBWF1 mouse model of systemic lupus erythematosus. 2020;11(6):5266-74.
47. Dhawan UK, Bhattacharya P, Narayanan S, Manickam V, Aggarwal A, Subramanian M. Hypercholesterolemia Impairs Clearance of Neutrophil Extracellular Traps and Promotes Inflammation and Atherosclerotic Plaque Progression. Arterioscler Thromb Vasc Biol. 2021;41(10):2598-615.
48. Choi JW, Pai SH. Influences of hypercholesterolemia on red cell indices and erythrocyte sedimentation rate in elderly persons. Clin Chim Acta. 2004;341(1-2):117-21.
49. Emorinken A, Dic-Ijiewere MO, Erameh CO, Ugheoke AJ, Agbadaola OR, Agbebaku FO. Clinical and laboratory profile of systemic lupus erythematosus patients at a rural tertiary centre in South-South Nigeria: experience from a new rheumatology clinic. Reumatologia. 2021;59(6):402-10.
50. Logar D, Kveder T, Rozman B, Dobovisek J. Possible association between anti-Ro antibodies and myocarditis or cardiac conduction defects in adults with systemic lupus erythematosus. Ann Rheum Dis. 1990;49(8):627-9.
51. Silverman GJ, Azzouz DF, Alekseyenko AVJCoii. Systemic Lupus Erythematosus and dysbiosis in the microbiome: cause or effect or both? 2019;61:80-5.
52. Chen Bd, Jia Xm, Xu Jy, Zhao Ld, Ji Jy, Wu Bx, et al. An autoimmunogenic and proinflammatory profile defined by the gut microbiota of patients with untreated systemic lupus erythematosus. 2021;73(2):232-43.
53. Spiljar M, Merkler D, Trajkovski MJFii. The immune system bridges the gut microbiota with systemic energy homeostasis: focus on TLRs, mucosal barrier, and SCFAs. 2017;8:1353.
54. Kasubuchi M, Hasegawa S, Hiramatsu T, Ichimura A, Kimura IJN. Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. 2015;7(4):2839-49.
55. Nastasi C, Candela M, Bonefeld CM, Geisler C, Hansen M, Krejsgaard T, et al. The effect of short-chain fatty acids on human monocyte-derived dendritic cells. 2015;5(1):16148.
56. Mazruei Arani N, Emam-Djomeh Z, Tavakolipour H, Sharafati-Chaleshtori R, Soleimani A, Asemi ZJP, et al. The effects of probiotic honey consumption on metabolic status in patients with diabetic nephropathy: a randomized, double-blind, controlled trial. 2019;11:1195-201.
57. Kinoshita A, Onoda H, Imai N, Nishino H, Tajiri HJH-g. C-Reactive Protein as a Prognostic Marker in Patients with Hepatocellular Carcinoma. 2015;62(140):966-70.
58. Mazidi M, Rezaie P, Ferns GA, Vatanparast HJN. Impact of probiotic administration on serum C-reactive protein concentrations: systematic review and meta-analysis of randomized control trials. 2017;9(1):20.
59. Wolfe F, Cathey MJTJoR. The assessment and prediction of functional disability in rheumatoid arthritis. 1991;18(9):1298-306.
60. Widhani A, Djauzi S, Suyatna FD, Dewi BEJC. Changes in gut microbiota and systemic inflammation after synbiotic supplementation in patients with systemic lupus erythematosus: a randomized, double-blind, placebo-controlled trial. 2022;11(21):3419.
61. Sakata TJASJ. Pitfalls in short‐chain fatty acid research: a methodological review. 2019;90(1):3-13.
