Background Systemic Sclerosis (SSc) is an autoimmune disease characterized by progressive deposition of extracellular matrix components in the skin and visceral organs (1). Recently, it has been shown that microbial translocation plays an important role in immune system activation (2), and that dietary changes may affect gut microbiota, altering immune system activation and conditioning the development of several autoimmune diseases (3).
Objectives The aims of the study were to investigate: a) which serum biomarkers could be used to evaluate and monitor GI disease in SSc patients and b) if nutritional intervention may reduce GI involvement, immune system activation and, finally, improve clinical symptoms and quality of life of SSc patients.
Methods Thirty-eight SSc patients affected by GI involvement were enrolled in the study. At baseline. the following serum biomarkers were evaluated: intestinal-type fatty acid-binding protein (I-FABP), lipopolysaccharide (LPS), and soluble CD14 (sCD14) serum levels, markers of enterocyte damage, microbial translocation and immune system activation, respectively. Moreover, in each examination clinical symptoms and patient's reported outcomes (SF-36) were collected.
After six months from the assumption of a mediterranean diet with low introduction of meat and diary products (4), clinical symptoms and SF-36 were evaluated in all patients and sCD14, LPS and I-FABP in 14 SSc patients. Twenty-five normal subjects constituted the control group.
Results At baseline, sCD14, LPS, and I-FABP resulted significantly higher in sera of SSc patients than healthy controls (Fig. 1A), and there was a strong correlation between sCD14/ I-FABP and LPS/I-FABP serum levels (Fig. 1B).
Higher LPS plasma levels (β=10.2, 95% CI (2.6, 17.9), p=0.01, R2 =0.17), but not sCD14 and I-FABP, were associated with the presence of Small Intestine Bacterial Overgrowth (SIBO). There were no statistical differences between patients with and/or without elevated bowel transit time, as assessed by lactulose breath test.
After 6 months of diet, a significant decrease of sCD14, LPS and I-FABP was observed and patients reported a consistent improvement of GI symptoms as well as of the quality of life (Fig. 1A-D).
Conclusions This work suggests that GI damage, and the consequent microbial translocation, triggers immune system activation and sustain clinical symptoms in SSc patients. Moreover, specific nutritional intervention significantly improves the clinical symptoms and the GI damage (I-FABP), thus reducing microbial translocation (LPS) and immune system activation (sCD14).
Gut microbioma and microbial translocation may play an important role in the activation of the immune system and, thus, in the pathogenesis of SSc disease.
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Disclosure of Interest None declared