Bacterial infections in lupus: Roles in promoting immune activation and in pathogenesis of the disease

Battaglia, Michael; Garrett‐Sinha, Lee Ann

doi:10.1016/j.jtauto.2020.100078

Cited by 23 publications

(17 citation statements)

References 161 publications

(144 reference statements)

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“…In a previous study, significant depletion of Lactobacillus was found in lupus-susceptible female mice compared to that in age-matched healthy female mice [ 6 ]. In addition, studies have shown that Escherichia infection is common in patients with SLE [ 18 – 20 ].…”

Section: Discussionmentioning

confidence: 99%

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Proton pump inhibitors induce changes in the gut microbiome composition of systemic lupus erythematosus patients

Chu

Cao

et al. 2022

BMC Microbiol

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Background Currently, few studies focus on the association between gut microbiota and systemic lupus erythematosus (SLE), and much less studies consider the effect of drug usage. Proton pump inhibitors (PPIs) are commonly used to treat drug-related gastrointestinal damage in SLE patients. Therefore, the purpose of this study is to examine the gut microbiota of SLE patients using PPIs. Methods Fecal samples from 20 SLE patients with PPIs (P-SLE), 20 SLE patients without PPIs (NP-SLE) and 17 healthy controls (HCs) were obtained. The structure of the bacterial community in the fecal samples was analyzed by 16S rRNA gene sequencing. Redundancy analysis (RDA) was performed to observe the relationship between clinical variables and microbiome composition in P-SLE and NP-SLE patients. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, functional capabilities of microbiota were estimated. Network analysis was performed to analyze the association of metabolic pathway alterations with altered gut microbiota in P-SLE and NP-SLE patients. Results P-SLE patients exhibited increased alpha-diversity and an altered composition of the gut microbiota compared with NP-SLE patients. The alpha-diversity of NP-SLE patients was significantly lower than HCs but also of P-SLE patients, whose alpha-diversity had become similar to HCs. Compared with NP-SLE patients, the relative abundances of Lactobacillus, Roseburia, Oxalobacter, and Desulfovibrio were increased, while those of Veillonella, Escherichia, Morganella, Pseudomonas and Stenotrophomonas were decreased in P-SLE patients. RDA indicated that PPI use was the only significant exploratory variable for the microbiome composition when comparing SLE patients. KEGG analysis showed that 16 metabolic pathways were significantly different between NP-SLE and P-SLE patients. These metabolic pathways were mainly associated with changes in Escherichia, Roseburia, Stenotrophomonas, Morganella and Alipipes as determined by the network analysis. Conclusions PPI use is associated with an improved microbiome composition of SLE patients as it 1) increases alpha-diversity levels back to normal, 2) increases the abundance of various (beneficial) commensals, and 3) decreases the abundance of certain opportunistic pathogenic genera such as Escherichia. Validation studies with higher patient numbers are however recommended to explore these patterns in more detail.

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Section: Discussionmentioning

confidence: 99%

“…Notably, previous studies have found that the relative abundance of Prevotellaceae were higher in SLE patients than in HCs [ 5 , 18 ]. In contrast, in our results, Prevotellaceae were reduced in NP-SLE patients, restored to some extent in P-SLE patients, and were highly abundant in HCs.…”

Section: Discussionmentioning

confidence: 99%

Proton pump inhibitors induce changes in the gut microbiome composition of systemic lupus erythematosus patients

Chu

Cao

et al. 2022

BMC Microbiol

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“…The role of the microbiome (as well as microbial infections) in individuals with existing SLE has been supported by a recent review [153], though much of this research is based on animal models. Microbes (and the metabolites they produce) can induce epigenetic modifications, thus contributing to immune cells and cytokine regulation and dysfunction [154,155].…”

Section: Infectionsmentioning

confidence: 99%

The role of environmental exposures and gene–environment interactions in the etiology of systemic lupus erythematous

et al. 2022

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Systemic lupus erythematosus (SLE) is a complex, chronic autoimmune disease, whose etiology includes both genetic and environmental factors. Individual genetic risk factors likely only account for about one‐third of observed heritability among individuals with a family history of SLE. A large portion of the remaining risk may be attributable to environmental exposures and gene–environment interactions. This review focuses on SLE risk associated with environmental factors, ranging from chemical and physical environmental exposures to lifestyle behaviors, with the weight of evidence supporting positive associations between SLE and occupational exposure to crystalline silica, current smoking, and exogenous estrogens (e.g., oral contraceptives and postmenopausal hormones). Other risk factors may include lifestyle behaviors (e.g., dietary intake and sleep) and other exposures (e.g., ultraviolet [UV] radiation, air pollution, solvents, pesticides, vaccines and medications, and infections). Alcohol use may be associated with decreased SLE risk. We also describe the more limited body of knowledge on gene–environment interactions and SLE risk, including IL‐10, ESR1, IL‐33, ITGAM, and NAT2 and observed interactions with smoking, UV exposure, and alcohol. Understanding genetic and environmental risk factors for SLE, and how they may interact, can help to elucidate SLE pathogenesis and its clinical heterogeneity. Ultimately, this knowledge may facilitate the development of preventive interventions that address modifiable risk factors in susceptible individuals and vulnerable populations.

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“…An enrichment of commensals that damage gut integrity has been detected in SLE patients and mouse models, such as R. gnavus and E. gallinarium ( 28 , 30 ). The combination of a defective immunity and the use of immunosuppressive drugs lead to a high frequency of pathogenic infections in SLE patients, including with Staphylococcus aureus , Salmonella enterica , Escherichia coli , Streptococcus pneumonia and Mycobacterial species ( 89 ). Salmonella typhimurium showed a capacity to increase gut permeability by upregulating the expression of Claudin-2, a leaky gut mediator ( 90 ).…”

Section: Mechanisms Leading To the Loss Of Barrier Integrity In Lupusmentioning

confidence: 99%

Loss of Gut Barrier Integrity In Lupus

Morel²

2022

Front. Immunol.

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Systemic Lupus Erythematosus is a complex autoimmune disease and its etiology remains unknown. Increased gut permeability has been reported in lupus patients, yet whether it promotes or results from lupus progression is unclear. Recent studies indicate that an impaired intestinal barrier allows the translocation of bacteria and bacterial components into systemic organs, increasing immune cell activation and autoantibody generation. Indeed, induced gut leakage in a mouse model of lupus enhanced disease characteristics, including the production of anti-dsDNA antibody, serum IL-6 as well as cell apoptosis. Gut microbiota dysbiosis has been suggested to be one of the factors that decreases gut barrier integrity by outgrowing harmful bacteria and their products, or by perturbation of gut immune homeostasis, which in turn affects gut barrier integrity. The restoration of microbial balance eliminates gut leakage in mice, further confirming the role of microbiota in maintaining gut barrier integrity. In this review, we discuss recent advances on the association between microbiota dysbiosis and leaky gut, as well as their influences on the progression of lupus. The modifications on host microbiota and gut integrity may offer insights into the development of new lupus treatment.

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Bacterial infections in lupus: Roles in promoting immune activation and in pathogenesis of the disease

Cited by 23 publications

References 161 publications

Proton pump inhibitors induce changes in the gut microbiome composition of systemic lupus erythematosus patients

Proton pump inhibitors induce changes in the gut microbiome composition of systemic lupus erythematosus patients

The role of environmental exposures and gene–environment interactions in the etiology of systemic lupus erythematous

Loss of Gut Barrier Integrity In Lupus

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