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

Abstract

BackgroundAltered 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.MethodsForty-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.ResultsSevere 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.ConclusionsSevere 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.

Gut dysbiosis is prevailing in Sjögren’s syndrome and is related to dry eye severity

“…In our study, gut dysbiosis were only noted in Sjögren's syndrome while patients with environmental dry eye syndrome maintained similar gut microbiota compositions with those of healthy volunteers. Although, studies for gut microbiota in Sjögren's syndrome have not been conducted much so far, this dysbiosis can be supported by previous studies [20,21]. One study reported that gut dysbiosis was prevalent in Sjögren's syndrome and was associated with systemic severity, but they did not mention how the composition of the gut microbiota changed [21].…”

“…Dysbiotic gut microbiome is also reported to be associated with ocular mucosal diseases in SS [20]. However, there are only few reports regarding the dysbiosis of the gut in Sjögren's syndrome [20,21]. Given that food habits and ethnicity may affect the gut microbiota, investigation of the gut microbiota of SS patients should be further conducted in different regions including Asia.…”

Environmental factors in the pathogenesis of primary Sjögren's syndrome

“…A study comparing patients with SS ( n = 39) and SLE ( n = 30) to population controls ( n = 965) found that faecal microbiota in both patient cohorts was characterized by lower bacterial richness and lower Firmicutes/Bacteroidetes ratios compared to controls . In another study, stool samples from 42 patients with SS and 35 age‐ and sex‐matched controls were analysed for dysbiosis using a 16s rRNA–microbiota test . Severe dysbiosis was significantly more prevalent in patients with SS than in controls (21% vs. 3%), and the patients with severe dysbiosis had higher ESSDAI scores, lower C4, and higher levels of faecal calprotectin.…”

Pulmonary and Bronchiolar Involvement in Sjogren's Syndrome

“…Gastrointestinal involvement in pSS 130 may lead to esophageal dysfunction, 131,132 gastroparesis, 133 gastroesophageal reflux, 134 atrophic gastritis, enteropathy, 135 pancreatic insufficiency, 136 hepatic involvement (including autoimmune hepatitis and fibrosis), [136][137][138] pseudolymphoma of the liver, 139 and dysbiosis (alteration of gut microbial flora). [140][141][142] SS may occur in combination with other autoimmune disorders such as PBC. 143 In a retrospective study of 125 patients with PBC, 77 (61.6%) had PBC only and 48 (38.4%) had both PBC and SS.…”