Changes in Gut Microbiota and Systemic Inflammation after Synbiotic Supplementation in Patients with Systemic Lupus Erythematosus: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Gut dysbiosis has a role in the pathogenesis of lupus. Synbiotic supplementation may restore the balance of gut microbiota. This study investigated whether synbiotics could improve gut microbiota and systemic inflammation in lupus patients. This randomized, double-blind, placebo-controlled trial was conducted in adult systemic lupus erythematosus (SLE) patients. Subjects were randomized to receive either synbiotics or a placebo. Fecal microbiota, hs-CRP, IL-6, and IL-17 were measured at baseline and after 60 days. Patients who fulfilled the inclusion criteria were randomized into synbiotic (n = 23) and placebo groups (n = 23). In the synbiotic group, hs-CRP was not significantly increased (1.8 [0.9; 4.85] vs. 2.1 [0.9; 4.25] mg/L; pre vs. post; p = 0.23), whereas in the placebo group hs-CRP was increased significantly (1.75 [0.4; 4.45] vs. 3.75 [0.58; 7.05] mg/L; pre vs. post; p = 0.005). In the synbiotic group, IL-6 decreased significantly (8.76 [6.62; 11.39] vs. 6.59 [4.96; 8.01]; pre vs. post; p = 0.02), while there was no significant change in IL-17 level. In the placebo group, there was no significant change in IL-6 and IL-17. Synbiotic supplementation increased the Firmicutes:Bacteroidetes ratio (0.05 ± 0.60 vs. -0.08 ± 0.63, synbiotic vs. placebo p = 0.48) and butyrate metabolism (p = 0.037) and decreased amino sugar and nucleotide sugar metabolism (p = 0.040). There was improvement in the SLE disease activity index 2K (SLEDAI-2K) score in the synbiotic group (14 [9; 16] vs. 8 [2; 12]; pre vs. post; p < 0.001), while no change in the placebo group (9 [8; 18.25] vs. 9 [5.5; 15]; pre vs. post; p = 0.31). Synbiotic supplementation could reduce systemic inflammation and SLE disease activity and alter the composition and functions of gut microbiota.

Keywords: inflammation; microbiota; probiotic; synbiotic; systemic lupus erythematosus.

Figure 1

Flowchart diagram of the study.

Figure 2

Changes after intervention in the synbiotic and placebo groups: (a) hs-CR; (b) IL-6; (c) IL-17.

Figure 3

(a) Rarefaction curves from the synbiotic treatment group and the placebo group; (b) Rank abundance curve of the 16s rRNA gene; (c) Principal coordinate analysis (PCoA) comparing the four groups.

Figure 4

Changes of alpha diversity parameters: (a) Richness index; (b) Chao 1 index; and (c) Shannon index in the synbiotic and placebo groups.

Figure 5

Changes in gut bacteria: (a) Class changes in the synbiotic group; (b) Class changes in the placebo group; (c) Comparison between the synbiotic and placebo group at the phylum level, before and after intervention; (d) Changes in Firmicutes/Bacteroidetes ratio.

Figure 5

Changes in gut bacteria: (a) Class changes in the synbiotic group; (b) Class changes in the placebo group; (c) Comparison between the synbiotic and placebo group at the phylum level, before and after intervention; (d) Changes in Firmicutes/Bacteroidetes ratio.

Figure 6

Changes in operational taxonomic units (OTUs): (a) Changes in OTU 107 and OTU 122; (b) Venn diagram showing the numbers of shared OTUs between groups; (c) Changes after intervention in both groups by heat map; (d) Average changes after intervention.

Figure 6

Changes in operational taxonomic units (OTUs): (a) Changes in OTU 107 and OTU 122; (b) Venn diagram showing the numbers of shared OTUs between groups; (c) Changes after intervention in both groups by heat map; (d) Average changes after intervention.

Figure 7

Changes in the functional prediction of gut microbiota after synbiotic supplementation.