The efficacy of probiotics, prebiotics or synbiotics in scleroderma: A systematic review.

INTRODUCTION: Pathogenesis of systemic scleroderma is a complex subject. Previous research has emphasized a possible contribution of the intestinal microbiome in developing symptoms. The use of probiotic formulas brings benefit in treatment of various autoimmune diseases, but the evidence for scleroderma is still not exhaustive. No official recommendations have been formulated on this topic, nor has the existing evidence been evaluated.

OBJECTIVE: We aimed to assess the efficacy of probiotics, prebiotics, or synbiotics in patients with scleroderma with a focus on the improvement of symptoms and change in the quality of life (QoL) both measured using validated scales, small intestinal bacterial overgrowth (SIBO) eradication, as well as change in the intensity of interstitial lung disease and occurrence of pulmonary hypertension.

METHODS: We performed a systematic search for randomized trials that assessed the beneficial and harmful effects of pro-, pre-, and synbiotics in patients with scleroderma. Pairs of authors independently selected studies for inclusion, extracted data, and assessed the risk of bias (RoB) of the included studies. We examined the certainty of evidence in accordance with the GRADE approach.

RESULTS: We screened 1801 references (after the removal of duplicates), and assessed 16 citations in full text. We identified four randomized controlled trials (RCTs) with 103 participants in intervention and 87 in control groups. The evidence suggests that probiotic intake may not affect gastrointestinal symptoms measured with Visual Analogue Scale for Gastrointestinal Tract (VAS-GIT) (change in the VAS-GIT: MD 0.04, 95% CI -0.31 to 0.40, low certainty, n = 56 probiotic group, n = 57 placebo group) and the evidence is very uncertain about the effect on gastrointestinal symptoms measured with The University of California Los Angeles Scleroderma Clinical Trial Consortium GIT 2.0 instrument (UCLA GIT 2.0) (change in the UCLA GIT 2.0 - total score: MD -0.18 95% CI -0.44, 0.07, very low certainty, n = 76 probiotic group, n = 74 placebo group). Meta-analysis showed that probiotic intake may slightly improve the social functioning measured with UCLA GIT 2.0 compared to placebo (MD -0.21, 95% CI -0.32 to -0.10, low certainty, n = 57 probiotic group, n = 53 placebo group), yet may result in little to no difference in physical functioning measured with Health Assessment Questionnaire-Disability Index (HAQ-DI) (MD 0.08, 95% CI -0.15 to 0.32, low certainty, n = 56 probiotic group, n = 57 placebo group) and frequency of adverse events, change in QoL and SIBO eradication. We did not find any studies addressing the effect of pro-, pre-, or synbiotics on interstitial lung disease or pulmonary hypertension. The certainty of evidence was low to very low mainly due to high RoB (lack of blinding, incomplete reporting) and imprecision.

- CONCLUSIONS: We were unable to definitively prove a positive or negative effect of probiotic intake in patients with systemic sclerosis. The results should be interpreted with caution due to low or very low certainty of evidence and would need more confirmation from strain and dose specific RCTs at a lower RoB.