3.1 Description of the included studies
Studies were evaluated against selection criteria. Finally, nine studies involving a total of 1817 patients were included in the present systematic review. The flow chart of research selection is shown in Figure 1[19].
3.2 Study characteristics
Table 1 provides an overview of the studies included in this systematic review, which consisted of nine case-control studies comparing the discrepancies in gut microbiota between primary Sjogren’s syndrome patients and healthy controls. The total sample size across all ten studies was 1817 participants, comprising 504 case groups and 1313 control groups. Nine studies included compared discrepancies in gut microbiota between primary Sjogren’s syndrome patients and health controls [20-28]. Seven of the nine studies included were from China[20, 22-25, 27, 28], while the others were from the Netherlands and Spain[21, 26]. Of these, there studies were published before 2021[21, 23, 26], while the remaining six were published after 2021[20, 22, 24, 25, 27, 28]. Two studies[29, 30] included only women. Participants in both groups were mainly women. The patients in both groups were diagnosed with primary Sjogren’s syndrome according to the diagnostic criteria set by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR), known as ACR-EULAR criteria. The criteria were established to ensure consistent and accurate diagnosis of primary Sjogren’s syndrome. The main outcome was the difference of fecal gut microbiota.
3.3 Discrepant gut microbiota diversity between primary Sjogren’s syndrome and healthy controls
In terms of the diversity of gut microbiota, we observed that six studies indicate significantly lower α-diversity of gut microbiota in patients with primary Sjogren’s syndrome compared to the healthy control group[13, 28, 29, 31-33]. Two studies suggested a significant difference in α-diversity between the two groups[30, 35], while one study indicated a significant increase in α-diversity[20]. Out of the nine included studies, seven studies indicated a significant difference in β-diversity between the two groups[20, 28-32, 36], while the remaining two studies showed no statistical significance in β-diversity[13, 35]. (Table 2).
3.4 Discrepant gut microbiota compositions between primary Sjogren’s syndrome and healthy controls
Table 2 presents the differences in abundance of gut microbiota composition between patients with primary Sjogren’s syndrome and healthy individuals.
At the phylum level, the abundance of Proteobacteria was significantly increased in patients with primary Sjogren’s syndrome compared to the healthy control group, as evidenced in three studies[20, 29, 30, 32, 35]. Additionally, Bacteroidetes showed a significant increase in abundance across these three studies[13, 28, 29]. Firmicutes exhibited a significant decrease in abundance in two studies compared to the healthy controls[20, 35]. Remarkably, Actinobacteria showed contrasting results in four studies, with two studies reporting a significant increase in abundance[30, 35], while the other two studies showed a significant decrease in abundance[20, 28]. The ratio of Firmicutes/Bacteroidetes showed a significant decrease in abundance across three studies. [13, 20, 28].
At the genus level, based on two or more studies, Prevotella was reported to exhibit a significant increase in abundance in two studies[29, 30], while one study reported a significant decrease in its abundance[35].Veillonella showed a significant increase in abundance across four studies[20, 29, 32, 35]. Bacteroides exhibited a significant increase in abundance in three studies[13, 20, 35], while it showed a significant decrease in abundance[29]. Similarly, Bifidobacterium and Faecalibacterium showed a significant increase in abundance[30], while a significant decrease was reported in the study[29].Escherichia-Shigella demonstrated a significant increase in abundance across three studies[30, 32, 35]. Dorea and Lachnospira showed a significant decrease in abundance compared to the healthy control group in two studies[20, 29].
At Family level, according to the results reported in two or more studies, Veillonellaceae showed a significant increase in abundance in two studies[29, 30]. Lachnospiraceae exhibited a significant increase in abundance in one study[32], while it showed a significant decrease in abundance in three other studies[29, 30, 35]. Bacteroidaceae showed a significant increase in abundance in three studies[20, 30, 35], while one study reported a significant decrease in abundance[29]. Enterobacteriaceae demonstrated a significant increase in abundance across four studies[29, 30, 32, 35].
At the species level, Escherichia coli exhibited a significant increase in abundance in two studies[29, 32]. Faecalibacterium prausnitzii showed a significant decrease in abundance in two studies[29, 31].
3.5 Secondary outcomes
The included literature stated a correlation between gut microbiota composition and clinical parameters (Table3). According to the results from two or more studies, Roseburia has been shown to have a negative correlation with disease activity, as well as a negative correlation with IL-12 and IL-6[29, 36].
3.6 Risk of bias and publication bias
This passage reports on the NOS (Newcastle-Ottawa Scale) assessment results of all comparative studies included in the systematic review. Table 4 summarizes these results, and it indicates that all studies presented a low risk of bias. This suggests that the included studies were conducted rigorously, and the risk of bias was low, indicating that the studies were of high quality and the results can be considered reliable.