The Effect of Probiotic Yogurt Containing Lactobacillus rhamnosus and Bifidobacterium bifidum on Disease Activity and Disability in Patients with Systemic Lupus Erythematosus: A Randomized Controlled Trial
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with relapsing and remitting periods.
Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with relapsing and remitting periods. It has been reported that alterations of gut microbiota can affect disease activity in SLE. Probiotics which can modify the gut microbiota may be useful to control disease activity. Therefore, the effect of probiotic yogurt was evaluated on SLE disease activity.
In this triple-blind, randomized, controlled trial, the patients were randomized and divided into 2 groups. The patients had Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) ≤6 and were on a stable dose of immunosuppressant in the last 3 months. The intervention group was given 200 g of probiotic yogurt containing Lactobacillus rhamnosus and Bifidobacterium bifidum for 13 weeks. The control group was given 200 g of yogurt without bacteria for 13 weeks. Demographic measurements, SLEDAI, and Health Assessment Questionnaire (HAQ) were analyzed before and after the intervention. The probiotic group (19 patients) and the control group (14 individuals) were compared. At the beginning and baseline of the trial, the probiotic and control groups’ average energy intake, micronutrients, and macronutrients did not differ significantly.
In the probiotic group, the amount of protein, cholesterol, magnesium, zinc, selenium, and iron intake increased significantly after intervention. There are no significant changes in SLEDAI score and disability (HAQ) between case and control groups at the end of the study.
Consumption of probiotic yogurt containing L rhamnosus and B bifidum did not have a significant short-term effect on SLEDAI and disability in SLE patients.
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2. Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med. 2008;358(9):929-39.
3. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725.
4. Swaak AJ, Nossent JC, Bronsveld W, van Rooyen A, Nieuwenhuys EJ, Theuns L, et al. Systemic lupus erythematosus. II. Observations on the occurrence of exacerbations in the disease course: Dutch experience with 110 patients studied prospectively. Ann Rheum Dis. 1989;48(6):455-60.
5. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum. 1992;35(6):630-40.
6. Romero-Diaz J, Isenberg D, Ramsey-Goldman R. Measures of adult systemic lupus erythematosus: updated version of British Isles Lupus Assessment Group (BILAG 2004), European Consensus Lupus Activity Measurements (ECLAM), Systemic Lupus Activity Measure, Revised (SLAM-R), Systemic Lupus Activity Questionnaire for Population Studies (SLAQ), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Arthritis Care Res (Hoboken). 2011;63 Suppl 11(0 11):S37-46.
7. Mosca M, Bombardieri S. Assessing remission in systemic lupus erythematosus. Clin Exp Rheumatol. 2006;24(6 Suppl 43):S-99-104.
8. Goswami RP, Sit H, Ghosh P, Sircar G, Ghosh A. Steroid-free remission in lupus: myth or reality; an observational study from a tertiary referral centre. Clin Rheumatol. 2019;38(4):1089-97.
9. Boomsma MM, Bijl M, Stegeman CA, Kallenberg CG, Hoffman GS, Tervaert JW. Patients' perceptions of the effects of systemic lupus erythematosus on health, function, income, and interpersonal relationships: a comparison with Wegener's granulomatosis. Arthritis Rheum. 2002;47(2):196-201.
10. Okada H, Kuhn C, Feillet H, Bach JF. The 'hygiene hypothesis' for autoimmune and allergic diseases: an update. Clin Exp Immunol. 2010;160(1):1-9.
11. Wei F, Xu H, Yan C, Rong C, Liu B, Zhou H. Changes of intestinal flora in patients with systemic lupus erythematosus in northeast China. PLoS One. 2019;14(3):e0213063.
12. Meng X, Zhou HY, Shen HH, Lufumpa E, Li XM, Guo B, et al. Microbe-metabolite-host axis, two-way action in the pathogenesis and treatment of human autoimmunity. Autoimmun Rev. 2019;18(5):455-75.
13. Azzouz D, Omarbekova A, Heguy A, Schwudke D, Gisch N, Rovin BH, et al. Lupus nephritis is linked to disease-activity associated expansions and immunity to a gut commensal. Ann Rheum Dis. 2019;78(7):947-56.
14. Huang C, Yi P, Zhu M, Zhou W, Zhang B, Yi X, et al. Safety and efficacy of fecal microbiota transplantation for treatment of systemic lupus erythematosus: An EXPLORER trial. J Autoimmun. 2022;130:102844.
15. Zhang L, Qing P, Yang H, Wu Y, Liu Y, Luo Y. Gut Microbiome and Metabolites in Systemic Lupus Erythematosus: Link, Mechanisms and Intervention. Front Immunol. 2021;12:686501.
16. McLoughlin RF, Berthon BS, Jensen ME, Baines KJ, Wood LG. Short-chain fatty acids, prebiotics, synbiotics, and systemic inflammation: a systematic review and meta-analysis. Am J Clin Nutr. 2017;106(3):930-45.
17. Liu T, Li J, Liu Y, Xiao N, Suo H, Xie K, et al. Short-chain fatty acids suppress lipopolysaccharide-induced production of nitric oxide and proinflammatory cytokines through inhibition of NF-κB pathway in RAW264.7 cells. Inflammation. 2012;35(5):1676-84.
18. Vinolo MA, Rodrigues HG, Nachbar RT, Curi R. Regulation of inflammation by short chain fatty acids. Nutrients. 2011;3(10):858-76.
19. Thangaraju M, Cresci GA, Liu K, Ananth S, Gnanaprakasam JP, Browning DD, et al. GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res. 2009;69(7):2826-32.
20. Didari T, Solki S, Mozaffari S, Nikfar S, Abdollahi M. A systematic review of the safety of probiotics. Expert Opin Drug Saf. 2014;13(2):227-39.
21. Mu Q, Zhang H, Liao X, Lin K, Liu H, Edwards MR, et al. Control of lupus nephritis by changes of gut microbiota. Microbiome. 2017;5(1):73.
22. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25(11):1271-7.
23. Castrejón I, Tani C, Jolly M, Huang A, Mosca M. Indices to assess patients with systemic lupus erythematosus in clinical trials, long-term observational studies, and clinical care. Clin Exp Rheumatol. 2014;32(5 Suppl 85):S-85-95.
24. Brigden ML. Clinical utility of the erythrocyte sedimentation rate. Am Fam Physician. 1999;60(5):1443-50.
25. Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. Arthritis Rheum. 1980;23(2):137-45.
26. Poole JL, Steen VD. The use of the Health Assessment Questionnaire (HAQ) to determine physical disability in systemic sclerosis. Arthritis Care Res. 1991;4(1):27-31.
27. 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. Trials. 2022;23(1):180.
28. Ruiz L, López P, Suárez A, Sánchez B, Margolles A. The role of gut microbiota in lupus: what we know in 2018? Expert Rev Clin Immunol. 2018;14(10):787-92.
29. Yao K, Xie Y, Wang J, Lin Y, Chen X, Zhou T. Gut microbiota: a newly identified environmental factor in systemic lupus erythematosus. Front Immunol. 2023;14:1202850.
30. Vallianou NG, Stratigou T, Tsagarakis S. Metformin and gut microbiota: their interactions and their impact on diabetes. Hormones (Athens). 2019;18(2):141-4.
31. Katz-Agranov N, Zandman-Goddard G. The microbiome links between aging and lupus. Autoimmun Rev. 2021;20(3):102765.
32. Cuervo A, Hevia A, López P, Suárez A, Sánchez B, Margolles A, et al. Association of polyphenols from oranges and apples with specific intestinal microorganisms in systemic lupus erythematosus patients. Nutrients. 2015;7(2):1301-17.
33. Toumi E, Goutorbe B, Plauzolles A, Bonnet M, Mezouar S, Militello M, et al. Gut microbiota in systemic lupus erythematosus patients and lupus mouse model: a cross species comparative analysis for biomarker discovery. Front Immunol. 2022;13:943241.
34. Li Y, Wang HF, Li X, Li HX, Zhang Q, Zhou HW, et al. Disordered intestinal microbes are associated with the activity of Systemic Lupus Erythematosus. Clin Sci (Lond). 2019;133(7):821-38.
35. Mohd R, Chin SF, Shaharir SS, Cham QS. Involvement of Gut Microbiota in SLE and Lupus Nephritis. Biomedicines. 2023;11(3).
36. Toumi E, Mezouar S, Plauzolles A, Chiche L, Bardin N, Halfon P, et al. Gut microbiota in SLE: from animal models to clinical evidence and pharmacological perspectives. Lupus Sci Med. 2023;10(1).
37. Shida K, Nanno M, Nagata S. Flexible cytokine production by macrophages and T cells in response to probiotic bacteria: a possible mechanism by which probiotics exert multifunctional immune regulatory activities. Gut Microbes. 2011;2(2):109-14.
38. Esmaeili SA, Mahmoudi M, Momtazi AA, Sahebkar A, Doulabi H, Rastin M. Tolerogenic probiotics: potential immunoregulators in Systemic Lupus Erythematosus. J Cell Physiol. 2017;232(8):1994-2007.
39. Hatakka K, Martio J, Korpela M, Herranen M, Poussa T, Laasanen T, et al. Effects of probiotic therapy on the activity and activation of mild rheumatoid arthritis--a pilot study. Scand J Rheumatol. 2003;32(4):211-5.
40. Widhani A, Djauzi S, Suyatna FD, Dewi BE. Changes in Gut Microbiota and Systemic Inflammation after Synbiotic Supplementation in Patients with Systemic Lupus Erythematosus: A Randomized, Double-Blind, Placebo-Controlled Trial. Cells. 2022;11(21).
41. Yadav MK, Kumari I, Singh B, Sharma KK, Tiwari SK. Probiotics, prebiotics and synbiotics: Safe options for next-generation therapeutics. Appl Microbiol Biotechnol. 2022;106(2):505-21.
42. Gotay CC, Korn EL, McCabe MS, Moore TD, Cheson BD. Quality-of-life assessment in cancer treatment protocols: research issues in protocol development. J Natl Cancer Inst. 1992;84(8):575-9.
43. Wolfe F, Cathey MA. The assessment and prediction of functional disability in rheumatoid arthritis. J Rheumatol. 1991;18(9):1298-306.
44. Isenberg D, Ramsey-Goldman R. Assessing patients with lupus: towards a drug responder index. Rheumatology (Oxford). 1999;38(11):1045-9.
45. Pineda Mde L, Thompson SF, Summers K, de Leon F, Pope J, Reid G. A randomized, double-blinded, placebo-controlled pilot study of probiotics in active rheumatoid arthritis. Med Sci Monit. 2011;17(6):Cr347-54.
2. Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med. 2008;358(9):929-39.
3. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725.
4. Swaak AJ, Nossent JC, Bronsveld W, van Rooyen A, Nieuwenhuys EJ, Theuns L, et al. Systemic lupus erythematosus. II. Observations on the occurrence of exacerbations in the disease course: Dutch experience with 110 patients studied prospectively. Ann Rheum Dis. 1989;48(6):455-60.
5. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum. 1992;35(6):630-40.
6. Romero-Diaz J, Isenberg D, Ramsey-Goldman R. Measures of adult systemic lupus erythematosus: updated version of British Isles Lupus Assessment Group (BILAG 2004), European Consensus Lupus Activity Measurements (ECLAM), Systemic Lupus Activity Measure, Revised (SLAM-R), Systemic Lupus Activity Questionnaire for Population Studies (SLAQ), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Arthritis Care Res (Hoboken). 2011;63 Suppl 11(0 11):S37-46.
7. Mosca M, Bombardieri S. Assessing remission in systemic lupus erythematosus. Clin Exp Rheumatol. 2006;24(6 Suppl 43):S-99-104.
8. Goswami RP, Sit H, Ghosh P, Sircar G, Ghosh A. Steroid-free remission in lupus: myth or reality; an observational study from a tertiary referral centre. Clin Rheumatol. 2019;38(4):1089-97.
9. Boomsma MM, Bijl M, Stegeman CA, Kallenberg CG, Hoffman GS, Tervaert JW. Patients' perceptions of the effects of systemic lupus erythematosus on health, function, income, and interpersonal relationships: a comparison with Wegener's granulomatosis. Arthritis Rheum. 2002;47(2):196-201.
10. Okada H, Kuhn C, Feillet H, Bach JF. The 'hygiene hypothesis' for autoimmune and allergic diseases: an update. Clin Exp Immunol. 2010;160(1):1-9.
11. Wei F, Xu H, Yan C, Rong C, Liu B, Zhou H. Changes of intestinal flora in patients with systemic lupus erythematosus in northeast China. PLoS One. 2019;14(3):e0213063.
12. Meng X, Zhou HY, Shen HH, Lufumpa E, Li XM, Guo B, et al. Microbe-metabolite-host axis, two-way action in the pathogenesis and treatment of human autoimmunity. Autoimmun Rev. 2019;18(5):455-75.
13. Azzouz D, Omarbekova A, Heguy A, Schwudke D, Gisch N, Rovin BH, et al. Lupus nephritis is linked to disease-activity associated expansions and immunity to a gut commensal. Ann Rheum Dis. 2019;78(7):947-56.
14. Huang C, Yi P, Zhu M, Zhou W, Zhang B, Yi X, et al. Safety and efficacy of fecal microbiota transplantation for treatment of systemic lupus erythematosus: An EXPLORER trial. J Autoimmun. 2022;130:102844.
15. Zhang L, Qing P, Yang H, Wu Y, Liu Y, Luo Y. Gut Microbiome and Metabolites in Systemic Lupus Erythematosus: Link, Mechanisms and Intervention. Front Immunol. 2021;12:686501.
16. McLoughlin RF, Berthon BS, Jensen ME, Baines KJ, Wood LG. Short-chain fatty acids, prebiotics, synbiotics, and systemic inflammation: a systematic review and meta-analysis. Am J Clin Nutr. 2017;106(3):930-45.
17. Liu T, Li J, Liu Y, Xiao N, Suo H, Xie K, et al. Short-chain fatty acids suppress lipopolysaccharide-induced production of nitric oxide and proinflammatory cytokines through inhibition of NF-κB pathway in RAW264.7 cells. Inflammation. 2012;35(5):1676-84.
18. Vinolo MA, Rodrigues HG, Nachbar RT, Curi R. Regulation of inflammation by short chain fatty acids. Nutrients. 2011;3(10):858-76.
19. Thangaraju M, Cresci GA, Liu K, Ananth S, Gnanaprakasam JP, Browning DD, et al. GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res. 2009;69(7):2826-32.
20. Didari T, Solki S, Mozaffari S, Nikfar S, Abdollahi M. A systematic review of the safety of probiotics. Expert Opin Drug Saf. 2014;13(2):227-39.
21. Mu Q, Zhang H, Liao X, Lin K, Liu H, Edwards MR, et al. Control of lupus nephritis by changes of gut microbiota. Microbiome. 2017;5(1):73.
22. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25(11):1271-7.
23. Castrejón I, Tani C, Jolly M, Huang A, Mosca M. Indices to assess patients with systemic lupus erythematosus in clinical trials, long-term observational studies, and clinical care. Clin Exp Rheumatol. 2014;32(5 Suppl 85):S-85-95.
24. Brigden ML. Clinical utility of the erythrocyte sedimentation rate. Am Fam Physician. 1999;60(5):1443-50.
25. Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. Arthritis Rheum. 1980;23(2):137-45.
26. Poole JL, Steen VD. The use of the Health Assessment Questionnaire (HAQ) to determine physical disability in systemic sclerosis. Arthritis Care Res. 1991;4(1):27-31.
27. 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. Trials. 2022;23(1):180.
28. Ruiz L, López P, Suárez A, Sánchez B, Margolles A. The role of gut microbiota in lupus: what we know in 2018? Expert Rev Clin Immunol. 2018;14(10):787-92.
29. Yao K, Xie Y, Wang J, Lin Y, Chen X, Zhou T. Gut microbiota: a newly identified environmental factor in systemic lupus erythematosus. Front Immunol. 2023;14:1202850.
30. Vallianou NG, Stratigou T, Tsagarakis S. Metformin and gut microbiota: their interactions and their impact on diabetes. Hormones (Athens). 2019;18(2):141-4.
31. Katz-Agranov N, Zandman-Goddard G. The microbiome links between aging and lupus. Autoimmun Rev. 2021;20(3):102765.
32. Cuervo A, Hevia A, López P, Suárez A, Sánchez B, Margolles A, et al. Association of polyphenols from oranges and apples with specific intestinal microorganisms in systemic lupus erythematosus patients. Nutrients. 2015;7(2):1301-17.
33. Toumi E, Goutorbe B, Plauzolles A, Bonnet M, Mezouar S, Militello M, et al. Gut microbiota in systemic lupus erythematosus patients and lupus mouse model: a cross species comparative analysis for biomarker discovery. Front Immunol. 2022;13:943241.
34. Li Y, Wang HF, Li X, Li HX, Zhang Q, Zhou HW, et al. Disordered intestinal microbes are associated with the activity of Systemic Lupus Erythematosus. Clin Sci (Lond). 2019;133(7):821-38.
35. Mohd R, Chin SF, Shaharir SS, Cham QS. Involvement of Gut Microbiota in SLE and Lupus Nephritis. Biomedicines. 2023;11(3).
36. Toumi E, Mezouar S, Plauzolles A, Chiche L, Bardin N, Halfon P, et al. Gut microbiota in SLE: from animal models to clinical evidence and pharmacological perspectives. Lupus Sci Med. 2023;10(1).
37. Shida K, Nanno M, Nagata S. Flexible cytokine production by macrophages and T cells in response to probiotic bacteria: a possible mechanism by which probiotics exert multifunctional immune regulatory activities. Gut Microbes. 2011;2(2):109-14.
38. Esmaeili SA, Mahmoudi M, Momtazi AA, Sahebkar A, Doulabi H, Rastin M. Tolerogenic probiotics: potential immunoregulators in Systemic Lupus Erythematosus. J Cell Physiol. 2017;232(8):1994-2007.
39. Hatakka K, Martio J, Korpela M, Herranen M, Poussa T, Laasanen T, et al. Effects of probiotic therapy on the activity and activation of mild rheumatoid arthritis--a pilot study. Scand J Rheumatol. 2003;32(4):211-5.
40. Widhani A, Djauzi S, Suyatna FD, Dewi BE. Changes in Gut Microbiota and Systemic Inflammation after Synbiotic Supplementation in Patients with Systemic Lupus Erythematosus: A Randomized, Double-Blind, Placebo-Controlled Trial. Cells. 2022;11(21).
41. Yadav MK, Kumari I, Singh B, Sharma KK, Tiwari SK. Probiotics, prebiotics and synbiotics: Safe options for next-generation therapeutics. Appl Microbiol Biotechnol. 2022;106(2):505-21.
42. Gotay CC, Korn EL, McCabe MS, Moore TD, Cheson BD. Quality-of-life assessment in cancer treatment protocols: research issues in protocol development. J Natl Cancer Inst. 1992;84(8):575-9.
43. Wolfe F, Cathey MA. The assessment and prediction of functional disability in rheumatoid arthritis. J Rheumatol. 1991;18(9):1298-306.
44. Isenberg D, Ramsey-Goldman R. Assessing patients with lupus: towards a drug responder index. Rheumatology (Oxford). 1999;38(11):1045-9.
45. Pineda Mde L, Thompson SF, Summers K, de Leon F, Pope J, Reid G. A randomized, double-blinded, placebo-controlled pilot study of probiotics in active rheumatoid arthritis. Med Sci Monit. 2011;17(6):Cr347-54.
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How to Cite
1.
Banaki R, Faezi ST, Esmaeilzadeh A, Mahmoudi M, Farhadi E, Alikhani M. The Effect of Probiotic Yogurt Containing Lactobacillus rhamnosus and Bifidobacterium bifidum on Disease Activity and Disability in Patients with Systemic Lupus Erythematosus: A Randomized Controlled Trial. Iran J Allergy Asthma Immunol. 2025;:1-12.
