Alterations of the fecal and vaginal microbiomes in patients with systemic lupus erythematosus and their associations with immunological profiles

Abstract

BackgroundExploring the human microbiome in multiple body niches is beneficial for clinicians to determine which microbial dysbiosis should be targeted first. We aimed to study whether both the fecal and vaginal microbiomes are disrupted in SLE patients and whether they are correlated, as well as their associations with immunological features.MethodsA group of 30 SLE patients and 30 BMI-age-matched healthy controls were recruited. Fecal and vaginal samples were collected, the 16S rRNA gene was sequenced to profile microbiomes, and immunological features were examined.ResultsDistinct fecal and vaginal bacterial communities and decreased microbial diversity in feces compared with the vagina were found in SLE patients and controls. Altered bacterial communities were found in the feces and vaginas of patients. Compared with the controls, the SLE group had slightly lower gut bacterial diversity, which was accompanied by significantly higher bacterial diversity in their vaginas. The most predominant bacteria differed between feces and the vagina in all groups. Eleven genera differed in patients’ feces; for example, Gardnerella and Lactobacillus increased, whereas Faecalibacterium decreased. Almost all the 13 genera differed in SLE patients’ vaginas, showing higher abundances except for Lactobacillus. Three genera in feces and 11 genera in the vagina were biomarkers for SLE patients. The distinct immunological features were only associated with patients’ vaginal microbiomes; for example, Escherichia−Shigella was negatively associated with serum C4.ConclusionsAlthough SLE patients had fecal and vaginal dysbiosis, dysbiosis in the vagina was more obvious than that in feces. Additionally, only the vaginal microbiome interacted with patients’ immunological features.

Racial Differences in Plasma Microbial Translocation and Plasma Microbiome, Implications in Systemic Lupus Erythematosus Disease Pathogenesis

“…Furthermore, we found that blood enrichment of Shigella was increased in Black controls versus White controls and decreased in Black patients versus White patients. Vaginal Escherichia and Shigella enrichment was negatively associated with serum C4 in patients with SLE 41 . Thus, Shigella may have negative association with SLE in Black patients.…”

“…Vaginal Escherichia and Shigella enrichment was negatively associated with serum C4 in patients with SLE. 41 Thus, Shigella may have negative association with SLE in Black patients.…”

Systemic lupus erythematosus therapeutic strategy: From immunotherapy to gut microbiota modulation

“…However, a pilot study reported that human microbiota imbalance in SLE was associated with immunological characteristics of the patients, such as serum C4 levels, suggesting that normalization of the microbiota may restore dysregulated immunity in SLE patients [13] . Indicators of immune system health, such as impaired Tfh/Tfr, Th17/Treg ratios, and levels of inflammatory cytokines in mice and SLE patients, were also found to be associated with changes in gut microbiota composition [12] . All these data allow us to consider intestinal dysbiosis as an important element in the development of SLE, and efforts aimed at its normalization are quite suitable for the role of a new means of treating this disease.…”

“…The Ruminococcaceae family has also been found to produce SCFAs, and a decrease in these bacteria could lead to a reduction in SCFA production [92] . Another metabolite of gut bacteria, tryptophan, is also associated with the SLE severity, is metabolized differently in SLE patients, and may control the number of autoreactive helper T cells [12] . Dietary tryptophan was found to regulate the autoimmune system; a low dietary tryptophan prevented autoimmune disease in a mouse model of SLE, while a high dietary tryptophan exacerbated the disease [108] .…”

“…Some researchers believe that, in addition to environmental and genetic factors, the microbiota is also responsible for the pathogenesis of systemic lupus, although the mechanisms of its influence are not yet fully understood [12] . However, a pilot study reported that human microbiota imbalance in SLE was associated with immunological characteristics of the patients, such as serum C4 levels, suggesting that normalization of the microbiota may restore dysregulated immunity in SLE patients [13] .…”