Severe intestinal dysbiosis is prevalent in primary Sjögren's syndrome and is associated with systemic disease activity

Abstract

Background: Altered microbial composition of the intestine, commonly referred to as dysbiosis, has been associated with several autoimmune diseases including primary Sjögren's syndrome (pSS). The aims of the current study were to study the intestinal microbial balance in pSS and to identify clinical features associated with dysbiosis.

Methods: Forty-two consecutive pSS patients and 35 age-matched and sex-matched control subjects were included in the study in an open clinic setting. Stool samples were analyzed for intestinal dysbiosis using a validated 16S rRNA-based microbiota test (GA-map™ Dysbiosis Test; Genetic Analysis, Oslo, Norway). Dysbiosis and severe dysbiosis were defined in accordance with the manufacturer's instructions. Patients were evaluated with regard to disease activity (European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and Clinical ESSDAI (ClinESSDAI)). In addition, patients were examined for laboratory and serological features of pSS as well as fecal calprotectin levels. Furthermore, patients were investigated regarding patient-reported outcomes for pSS (EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI)) and irritable bowel syndrome (IBS)-like symptoms according to the Rome III criteria.

Results: Severe dysbiosis was more prevalent in pSS patients in comparison to controls (21 vs 3%; p = 0.018). Subjects with pSS and severe dysbiosis had higher disease activity as evaluated by the ESSDAI total score (13 vs 5; p = 0.049) and the ClinESSDAI total score (12 vs 5; p = 0.049), lower levels of complement component 4 (0.11 vs 0.17 g/L; p = 0.004), as well as higher levels of fecal calprotectin (110 vs 33 μg/g; p = 0.001) compared to the other pSS patients. In contrast, severe dysbiosis among pSS patients was not associated with disease duration, IBS-like symptoms, or the ESSPRI total score.

Conclusions: Severe intestinal dysbiosis is a prevalent finding in pSS and is associated both with clinical and laboratory markers of systemic disease activity as well as gastrointestinal inflammation. Further studies are warranted to elucidate a potential causative link between dysbiosis and pSS.

Keywords: Disease activity; Dysbiosis; Gastrointestinal; Microbiome; Primary Sjögren’s syndrome.

Fig. 1

Dysbiosis Index Score in primary Sjögren’s syndrome and age-matched and sex-matched control subjects. A subgroup of patients with severe dysbiosis (DIS 5) can be identified among the subjects with primary Sjögren’s syndrome (pSS) but not in the control group

Fig. 2

Disease activity (a), hypocomplementemia (b), and intestinal inflammation (c) in pSS subjects with and without severe dysbiosis, defined as a Dysbiosis Index Score 5. Patients with intestinal dysbiosis have higher ESSDAI scores (a), lower C4 levels (b), and higher levels of F-calprotectin (c) compared to other patients. Dot plot, median values marked by a horizontal line. *p < 0.05, **p < 0.005. EULAR European League Against Rheumatism