Systemic Lupus Erythematosus and dysbiosis in the microbiome: cause or effect or both?

Silverman, Gregg J.; Azzouz, Doua F.; Alekseyenko, Alexander V.

doi:10.1016/j.coi.2019.08.007

Cited by 54 publications

(40 citation statements)

References 30 publications

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“…Our report further explained the greater potential implications of host colonisation by R. gnavus 2 and this species has now been implicated in several inflammatory and autoimmune diseases (discussed by Silverman et al 6). Moreover, the link between R. gnavus with lupus, a disease with a strong hallmark of B-cell abnormalities and autoantibody production, may be intimately intertwined with the local production and postulated systemic release of a recently identified R. gnavus outer membrane protein with the properties of a B-cell superantigen 7.…”

supporting

confidence: 72%

Response to: ‘The level of peripheral regulatory T cells is linked to changes in gut commensal microflora in patients with systemic lupus erythematosus’ by Zhang et al and the phylogeny of a candidate pathobiont in lupus nephritis

Silverman

Azzouz

2019

Ann Rheum Dis

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supporting

confidence: 72%

Response to: ‘The level of peripheral regulatory T cells is linked to changes in gut commensal microflora in patients with systemic lupus erythematosus’ by Zhang et al and the phylogeny of a candidate pathobiont in lupus nephritis

Silverman

Azzouz

2019

Ann Rheum Dis

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“…In addition to experimental models, human studies add to the complexity of host-microbiome interactions in lupus and suggest that influences of lupus disease activity and gut dysbiosis may be bidirectional. 36 Specific strains of a gut commensal (like Ruminococcus gnavus of the Lachnospiraceae family), may contribute to the immune pathogenesis of lupus 17 ; alternatively, these shifts may be secondary, as immune activation and systemic inflammatory milieu could alter the metabolomic environment in the gut that drives dysbiotic shifts. 36 Decreased ratio of Firmicutes to Bacteroidetes compared to healthy controls is observed in lupus patients 37–39 while other studies demonstrated relative abundance of Lactobacillus species in lupus patients.…”

Section: Discussionmentioning

confidence: 99%

New insights in gut-liver axis in wild-type murine imiquimod-induced lupus

Maalouly

Hajal

Noujeim

et al. 2021

Lupus

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Background Intestinal and hepatic manifestations of lupus seem to be underestimated in comparison to other major organ lesions. Although recent data point to gut-liver axis involvement in lupus, gut permeability dysfunction and liver inflammation need to be more investigated. Objective This study aims to assess fecal calprotectin, intestinal tight junction proteins and liver inflammation pathway in wild-type murine imiquimod- induced lupus. Methods C57BL/6 mice were topically treated on their right ears with 1.25 mg of 5% imiquimod cream, three times per week for six weeks. Fecal calprotectin was collected at day 0, 22 and 45. Renal, liver and intestinal pathology, as well as inflammatory markers, intestinal tight junction proteins, and E. coli protein in liver were assessed at sacrifice. Results At six weeks, lupus nephritis was confirmed on histopathology and NGAL and KIM-1 expression. Calprotectin rise started at day 22 and persists at day 45. Protein expression of Claudine, ZO-1 and occludin was significantly decreased. E. coli protein was significantly increased in liver with necro-inflammation and increased TLR4, TLR7, and pNFκB/NFκB liver expression. Conclusion This study is the first to demonstrate early fecal calprotectin increase and liver activation of TLR4- NFκB pathway in wild-type murine imiquimod-induced lupus.

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“…Most SLE patients will develop either arthritis or synovitis sometime during their disease. A study on SLE patients showed an increased amounts of R. gnavus that correlated with disease activity, which was highest in the patients with lupus nephritis ( 83 – 85 ). One plausible mechanism for the contribution of R. gnavus in an inflammatory disease, CD, has been shown by Henke and colleagues ( 86 ).…”

Section: Putative Pathobionts In Hla-b27 Associated Spondyloarthropatmentioning

confidence: 99%

Putative Pathobionts in HLA-B27-Associated Spondyloarthropathy

Gill

Rosenbaum

2021

Front. Immunol.

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Spondyloarthritis (SpA) is a group of immune mediated inflammatory diseases with a strong association to the major histocompatibility (MHC) class I molecule, HLA-B27. Although the association between HLA-B27 and AS has been known for almost 50 years, the mechanisms underlying disease pathogenesis are elusive. Over the years, three hypotheses have been proposed to explain HLA-B27 and disease association: 1) HLA B27 presents arthritogenic peptides and thus creates a pathological immune response; 2) HLA-B27 misfolding causes endoplasmic reticulum (ER) stress which activates the unfolded protein response (UPR); 3) HLA-B27 dimerizes on the cell surface and acts as a target for natural killer (NK) cells. None of these hypotheses explains SpA pathogenesis completely. Evidence supports the hypothesis that HLA-B27-related diseases have a microbial pathogenesis. In animal models of various SpAs, a germ-free environment abrogates disease development and colonizing these animals with gut commensal microbes can restore disease manifestations. The depth of microbial influence on SpA development has been realized due to our ability to characterize microbial communities in the gut using next-generation sequencing approaches. In this review, we will discuss various putative pathobionts in the pathogenesis of HLA-B27-associated diseases. We pursue whether a single pathobiont or a disruption of microbial community and function is associated with HLA-B27-related diseases. Furthermore, rather than a specific pathobiont, metabolic functions of various disease-associated microbes might be key. While the use of germ-free models of SpA have facilitated understanding the role of microbes in disease development, future studies with animal models that mimic diverse microbial communities instead of mono-colonization are indispensable. We discuss the causal mechanisms underlying disease pathogenesis including the role of these pathobionts on mucin degradation, mucosal adherence, and gut epithelial barrier disruption and inflammation. Finally, we review the various uses of microbes as therapeutic modalities including pre/probiotics, diet, microbial metabolites and fecal microbiota transplant. Unravelling these complex host-microbe interactions will lead to the development of new targets/therapies for alleviation of SpA and other HLA-B27 associated diseases.

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Systemic Lupus Erythematosus and dysbiosis in the microbiome: cause or effect or both?

Cited by 54 publications

References 30 publications

Response to: ‘The level of peripheral regulatory T cells is linked to changes in gut commensal microflora in patients with systemic lupus erythematosus’ by Zhang et al and the phylogeny of a candidate pathobiont in lupus nephritis

Response to: ‘The level of peripheral regulatory T cells is linked to changes in gut commensal microflora in patients with systemic lupus erythematosus’ by Zhang et al and the phylogeny of a candidate pathobiont in lupus nephritis

New insights in gut-liver axis in wild-type murine imiquimod-induced lupus

Putative Pathobionts in HLA-B27-Associated Spondyloarthropathy

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