Disertasi

Pengaruh sinbiotik terhadap aktivitas penyakit, respons imun, serta permeabilitas dan mikrobiota usus pada pasien lupus eritematosus sistemik. = Effects of synbiotic supplementation on disease acivity, immune response, gut permeability, and microbiota of systemic lupus erythematosus patients.

Latar Belakang. Disbiosis saluran cerna berperan pada lupus eritematosus sistemik (SLE). Kondisi tersebut memengaruhi inflamasi sistemik dan keseimbangan Tregulator dan Th17. Penelitian ini bertujuan mengetahui efek sinbiotik terhadap aktivitas penyakit, respons imun, permeabilitas usus, dan mikrobiota usus pada pasien SLE. Metode. Penelitian ini merupakan uji klinis acak tersamar ganda dengan plasebo yang dilakukan di Rumah Sakit Cipto Mangunkusumo, Oktober 2017 hingga Agustus 2018. Subjek yang memenuhi kriteria inklusi dan menandatangani informed consent, dirandom ke dua kelompok: kelompok sinbiotik mendapat probiotik (Lactobacillus helveticus R0052 60%, Bifidobacterium infantis R0033 20%, Bifidobacterium bifidum R0071 20%) serta fructooligosaccharide 80 mg selama dua bulan serta kelompok plasebo. Skor Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K), interleukin 17 (IL-17), high sensitivity Creactive protein (hs-CRP), Tregulator, zonulin, dan 16s ribosomal ribonucleic acid (rRNA) sequencing dari sampel feses dinilai di awal dan akhir intervensi. Hasil. Dari 100 pasien, 46 pasien memenuhi kriteria inklusi dan diacak ke kelompok sinbiotik (n=23) dan plasebo (n=23). Semua pasien adalah perempuan. Median (interquartile range, IQR) usia adalah 35 (24; 40) tahun pada kelompok sinbiotik dan 27 (22; 40) tahun pada kelompok plasebo. Tidak ada perbedaan bermakna karakteristik awal dari segi usia, SLEDAI-2K, dosis steroid, obat penyerta (imunosupresan, vitamin D, penghambat pompa proton, statin), dan indeks massa tubuh. Sinbiotik menurunkan SLEDAI-2K. Pada kelompok sinbiotik median SLEDAI-2K (14(9; 16) vs 8(2; 12); pre vs post; p < 0,001). Pada kelompok plasebo median SLEDAI-2K (9(8; 18,25) vs 9(5,5; 15); pre vs post; p = 0,31). Sinbiotik menahan peningkatan hs-CRP. Pada kelompok sinbiotik median hs-CRP (1,8(0,9; 4,85) vs 2,1(0,9; 4,25) mg/L; pre vs post; p=0,23). Pada kelompok plasebo terjadi kenaikan hs-CRP (1,75(0,4; 4,45) vs 3,75(0,58; 7,05) mg/L; pre vs post; p=0,005). Sinbiotik meningkatkan rasio Firmicutes:Bacteroidetes (0,05±0,60 vs -0,08±0,63; p=0,48) dan metabolisme butirat (p=0,037). Simpulan. Suplementasi sinbiotik menurunkan aktivitas penyakit, menahan kenaikan hs-CRP, dan memperbaiki fungsi mikrobiota saluran cerna pada pasien SLE.
Kata kunci. sinbiotik, lupus, SLEDAI, hs-CRP.


Background. Gut dysbiosis has a role in the pathogenesis of systemic lupus erythematosus (SLE), causing systemic inflammation and affecting balance of regulatory T cells and Th17. This study was conducted to determine the effects of synbiotic on disease activity, immune response, gut permeability, and microbiota among SLE. Methods. This was a randomized double blind placebo-controlled trial conducted at Cipto Mangunkusumo Hospital from October 2017 to August 2018. Subjects with inclusion criteria and gave informed consent were randomized into two groups: synbiotic group which given probiotic (Lactobacillus helveticus R0052 60%, Bifidobacterium infantis R0033 20%, Bifidobacterium bifidum R0071 20%) and 80 mg fructooligosaccharide for two months and placebo group. During study, the patients continued their immunosuppressants. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K), interleukin 17 (IL-17), high sensitivity C-reactive protein (hs-CRP), regulatory T cell, zonulin, and 16s ribosomal ribonucleic acid (rRNA) sequencing from fecal sample were evaluated. Results. From 100 patients, 46 fulfilled inclusion criteria and randomized into synbiotic (n=23) and placebo groups (n=23). All patients were female. Median (IQR) age were 35 (24; 40) and 27 (22; 40) years old for synbiotic and placebo group respectively. At baseline, there was no significant difference between synbiotic and placebo groups regarding age, SLEDAI-2K, steroid dose, medications (immunosuppressant, vitamin D, proton pump inhibitor, statin), and body mass index. Synbiotic decreased SLEDAI-2K. In synbiotic group median SLEDAI-2K were (14(9;16) vs 8(2;12);pre vs post; p < 0.001). In placebo group median SLEDAI-2K were (9(8;18.25) vs 9(5.5;15);pre vs post;p = 0.31). Synbiotic dampened increased in hs-CRP. In synbiotic group median hs-CRP were (1.8(0.9;4.85) vs 2.1(0.9;4.25) mg/L;pre vs post;p=0.23) whereas in placebo group hs-CRP were increased (1.75(0.4;4.45) vs 3.75(0.58;7.05) mg/L pre vs post; p = 0.005). Synbiotic increased Firmicutes:Bacteroidetes ratio (0.05±0.60 vs 0.08±0.63,p = 0.48) and butyrate metabolism (p = 0.037). Conclusion. Synbiotic supplementation decreased disease activity, dampened increased in hs-CRP, and improved gut microbiota functions in SLE patients.
Keywords: synbiotic, lupus, SLEDAI, hs-CRP.