Association between systemic lupus erythematosus and disruption of gut microbiota: a meta-analysis

Abstract

ObjectiveRecent studies reported that SLE is characterised by altered interactions between the microbiome and immune system. We performed a meta-analysis of publications on this topic.MethodsCase–control studies that compared patients with SLE and healthy controls (HCs) and determined the diversity of the gut microbiota and the abundance of different microbes were examined. Stata/MP V.16 was used for the meta-analysis. A Bonferroni correction for multiple tests was used to reduce the likelihood of false-positive results.ResultsWe included 11 case–control studies that examined 373 patients with SLE and 1288 HCs. These studies were performed in five countries and nine cities. Compared with HCs, patients with SLE had gut microbiota with lower Shannon-Wiener diversity index (weighted mean difference=−0.22, 95% CI −0.32 to –0.13, p<0.001) and lower Chao1 richness (standardised mean difference (SMD)=−0.62, 95% CI −1.04 to –0.21, p=0.003). Patients with SLE had lower abundance of Ruminococcaceae (SMD = −0.49, 95% CI −0.84 to −0.15,p=0.005), but greater abundance of Enterobacteriaceae (SMD=0.45, 95% CI 0.01 to 0.89, p=0.045) and Enterococcaceae (SMD=0.53, 95% CI 0.05 to 1.01, p=0.03). However, only the results for Ruminococcaceae passed the Bonferroni correction (p=0.0071). The two groups had no significant differences in Lachnospiraceae and Bacteroides (both p>0.05). Patients with SLE who used high doses of glucocorticoids had altered gut microbiota based on the Chao1 species diversity estimator, and hydroxychloroquine use appeared to reduce the abundance of Enterobacteriaceae.ConclusionsPatients with SLE have imbalanced gut microbiota, with a decrease in beneficial bacteria and an increase in harmful bacteria. Drugs used to treat SLE may also alter the gut microbiota of these patients.

Loss of Gut Barrier Integrity In Lupus

“…Genetic factors, such as histocompatibility complex (MHC) polymorphism, and environmental factors, including ethnicity, diet and geography, have been correlated to the gut microbiota structure ( 19 – 21 ). A meta-analysis of studies comparing the fecal microbiome of SLE patients and healthy controls showed a lower diversity in SLE patients with a lower abundance of Ruminococcaceae ( 9 ). SLE patients with active lupus disease showed less diverse gut microbiota but a significantly higher abundance of the bacterial phylum Proteobacteria ( 22 ).…”

“…NSAIDs can induce mitochondrial and endoplasmic reticulum damage and oxidative stress in intestinal epithelial cells, enhancing gut permeability and local inflammation ( 110 ). Treatment of SLE patients with hydroxychloroquine reduced the abundance of Enterobacteriaceae , and glucocorticoids, a group of drugs broadly used to treat lupus, reduced microbial diversity ( 9 ). The calcineurin inhibitor tacrolimus (FK 506) increased gut permeability in humans and rats through inhibiting mitochondrial respiration in gut epithelial cells ( 111 ).…”

“…Ultraviolet light, air pollution, infections and exposure to heavy metals are the most common triggers that can influence lupus progression by modulating epigenetic factors, affecting host immune status, increasing oxidative stress, regulating hormone levels or changing the configuration of the host microbiome ( 6 ). Increasing evidence supports that an unbalanced gut microbiota is associated with lupus pathogenesis ( 7 – 9 ). Dietary intervention modulating the composition of the gut microbiota, such as butyrate, tryptophan or resistant starch reversed some lupus phenotypes in murine models ( 10 – 12 ).…”

Gut microbiota in systemic lupus erythematosus patients and lupus mouse model: a cross species comparative analysis for biomarker discovery

“…Their decrease may lead to leaky gut. Recently, a meta-analysis of relevant research publications from around the world has shown a decreased abundance of Ruminococcaceae with SLE, especially in Chinese patients ( 48 ). Overall, our results show that a specific microbial signature in patients with SLE with more severe dysbiosis was found and correlated strongly with the SLEDAI activity score, suggesting the contribution of gut microbiota to the severity of the disease.…”

Microbiome Changes in Connective Tissue Diseases and Vasculitis: Focus on Metabolism and Inflammation

“…It inhibits the growth of intestinal bacterial strains in a dose-dependent manner, which results in reduced stimulation of immune system activation and decreased tolerance to Treg cell induction [ 101 ]. In addition, the use of hydroxychloroquine in SLE appears to reduce the abundance of Enterobacteriaceae [ 102 ]. Concerning other standard treatment options, no significant data have emerged to date.…”