Background/Purpose:

Abnormalities in the intestinal microbiota have been associated with several autoimmune diseases, including systemic sclerosis (SSc). Recent studies have demonstrated the potential of probiotics in modulating the microbioma and the immune responses in several autoimmune diseases. T cell abnormalities including a predominant T helper type 2 (Th2) profile and increased levels of Th17 cells have been implicated in the pathogenesis of SSc. The objective of this study was to evaluate the effects of probiotics on the gastrointestinal (GI) symptoms and immune parameters in patients with SSc.

Methods:

In this double-blind, placebo-controlled, randomized clinical trial 73 patients with SSc (EULAR/ACR criteria from 2013) with a moderate-to-severe total score (0.5–3.00) on the University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument 2.0 (UCLA GIT 2.0) were randomized to receive probiotics (1 capsule/day of Lactobacillus paracasei, L. rhamnosus, L. acidophillus and Bifidobacterium lactis, 10⁹ colony-forming units per capsule) or placebo (identical capsules containing maltodextrin) for 8 weeks. The primary outcome measurement was improvement in the UCLA GIT 2.0 total score after 8 weeks of treatment. Secondary outcomes included changes in Th1, Th2, Th17 and regulatory T cells serum levels, immunoglobulin A (IgA), scleroderma Health Assessment Questionnaire (SHAQ) score, anthropometric parameters, and dietary intake. The frequencies of Th1 (CD3⁺CD8^–IFN-γ⁺), Th2 (CD3⁺CD8^–IL4⁺), Th17 (CD3⁺CD8^–IL17⁺) and regulatory T (CD3⁺CD4⁺CD25⁺Foxp3⁺) cells in peripheral blood were measured using flow cytometry. Clinical and immune parameters were assessed at baseline (T0), after four (T4) and eight weeks (T8) of treatment. The trial was registered on ClinicalTrials.com under the identifier NCT 02302352.

Results:

Thirty-seven patients were randomized to probiotics (mean age 47.7 years) and 36 (mean age 46.1 years) to the placebo group. After 8 weeks, there was a significant improvement in UCLA GIT 2.0 total score in both groups (p<0.001), but changes were not different between the two groups (p=0.934). The probiotic group presented a significant decrease in the serum percentage of Th2 (from 2.2% in T0 to 1.5% in T8) and Th17 (from 2.0% in T0 to 1.4% in T8) cells compared with the placebo group (from 2.3% in T0 to 2.5% in T8 for Th2; from 1.9% in T0 to 1.9% in T8 for Th17 cells) (p=0.038, p=0.04; respectively). No significant changes were observed in percentages of Th1 and Treg cells, IgA serum levels, SHAQ score, anthropometric parameters, and dietary intake after treatment between the two groups. No serious adverse events were reported.

Conclusion:

In this first randomized, double-blind trial evaluating the effects of probiotics in SSc, there was no reduction in the GI symptoms with probiotic supplementation compared with placebo. Nonetheless, probiotics showed to reduced the peripheral percentages of Th2 and Th17 cells in patients with SSc. These results indicate that probiotics have immunomodulatory effects and anti-inflammatory properties and might represent an innovative therapeutic approach to SSc patients.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/effect-of-probiotics-on-the-gastrointestinal-symptoms-and-immune-parameters-in-patients-with-systemic-sclerosis-a-randomized-double-blind-placebo-controlled-clinical-trial/