Intestinal barrier dysfunction plays an integral role in arthritis pathology and can be targeted to ameliorate disease

Matei, Diana E.; Menon, Madhvi; Alber, Dagmar; Smith, Andrew M.; Nedjat-Shokouhi, Bahman; Fasano, Alessio; Magill, L; Duhlin, Amanda; Bitoun, Samuel; Gleizes, Aude; Hacein‐Bey‐Abina, Salima; Manson, Jessica; Rosser, Elizabeth C.; Klein, Nigel; Blair, Paul A.; Mauri, Claudia

doi:10.1016/j.medj.2021.04.013

Cited by 49 publications

(61 citation statements)

References 68 publications

(117 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“… 52 , 53 , 54 This phenomenon had been reported in patients with rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus and other rheumatic diseases. 48 , 55 , 56 , 57 , 58 , 59 Abnormal gut barrier function may result in increased epithelial permeability, allowing microbial fragments and products to enter the sub-epithelial space and lamina propria. 60 Upon binding to specific receptors of antigen-presenting cells, these molecules will activate pro-inflammatory T cells (including T helper 1 and T helper 17 cells), thus inducing B cells to differentiate into autoantibody-producing plasma cells.…”

Section: Discussionmentioning

confidence: 99%

Gut dysbiosis in rheumatic diseases: A systematic review and meta-analysis of 92 observational studies

et al. 2022

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Gut dysbiosis in rheumatic diseases: A systematic review and meta-analysis of 92 observational studies

et al. 2022

View full text Add to dashboard Cite

“…Gut dysbiosis has been found to enhance barrier permeability and increase intestinal inflammation in animal models of arthritis, diabetes and obesity [24][25][26]. Changes of gut microbiota induce the low-grade inflammation through enhancing the resolution of some specific inflammatory factors like short-chain fatty acids (SCFAs), which are generated by fermentation of complex carbohydrates, or promoting the leakage of bacterial products such as LPS (lipopolysaccharide) [27].…”

Section: Gut-bone Marrow Axismentioning

confidence: 99%

Gut-disc axis: A cause of intervertebral disc degeneration and low back pain?

Lai

Chopra

et al. 2022

Eur Spine J

View full text Add to dashboard Cite

Purpose Low back pain (LBP), a widely prevalent and costly disease around the world, is mainly caused by intervertebral disc (IVD) degeneration (IDD). Although numerous factors may trigger this degenerative process, microbiome dysbiosis has recently been implicated as one of the likely causes. However, the exact relationship between the microbiome and IDD is not well understood. This review summarizes the potential mechanisms and discusses microbiome dysbiosis’s possible influence on IDD and LBP. Methods Prospective literature review. Results Alterations in microbiome composition and host responses to the microbiota causing pathological bone development and involution, led to the concept of gut-bone marrow axis and gut-bone axis. Moreover, the concept of the gut-disc axis was also proposed to explain the microbiome’s role in IDD and LBP. According to the existing evidence, the microbiome could be an important factor for inducing and aggravating IDD through changing or regulating the outside and inside microenvironment of the IVD. Three potential mechanisms by which the gut microbiota can induce IVD and cause LBP are: (1) translocation of the bacteria across the gut epithelial barrier and into the IVD, (2) regulation of the mucosal and systemic immune system, and (3) regulation of nutrient absorption and metabolites formation at the gut epithelium and its diffusion into the IVD. Furthermore, to investigate whether IVD is initiated by pathogenic bacteria and establish the correlation between the presence of certain microbial groups with the disease in question, microbiome diversity analysis based on16S rRNA data can be used to characterise stool/blood microbiota from IVD patients. Conclusion Future studies on microbiome, fungi and viruses in IDD is necessary to revolutionize our thinking about their possible role in the development of IVD diseases. Furthermore, we believe that inflammation inhibition and interruption of amplification of cascade reaction in IVD by targeting the gut and IVD microbiome is worthwhile for the treatment of IDD and LBP. Level of Evidence I Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.

show abstract

“…Our recent studies have shown that in a mouse model of spontaneous autoimmune lupus, proinflammatory phenotype of gut mucosa at as early as juvenile age correlates with the gender bias observed in lupus-like disease [13,28]. Pro-inflammatory events of the gut mucosa including higher gut permeability and microbial translocation have been implicated in systemic autoimmunity [15][16][17][18][19]. High levels of a pro-inflammatory factor, calprotectin were detected in the fecal samples of SLE patients [5].…”

Section: Discussionmentioning

confidence: 99%

“…Our preclinical studies using lupus-prone mice have shown: 1) that minor dietary deviations can alter the composition of gut microbiota and the lupus-like disease progression [9], 2) a potential contribution of proinflammatory immune response, including higher frequencies of plasma cells, initiated in the gut mucosa to the disease process and gender bias [12,13], and 3) higher frequencies of IgA autoantibody producing cells in the gut mucosa, and higher abundance and nAg reactivity of fecal IgA at pre-seropositive and -clinical stages [14]. Importantly, higher gut permeability and microbial translocation have been implicated in the initiation and/or progression of autoimmunity in at risk subjects [15][16][17][18][19]. These and other reports showing the involvement of gut microbiota in systemic autoimmune progression in lupus [6-8, 20, 21] suggest the need to determine if pro-inflammatory/gut permeability factors and IgA are produced and released at higher levels in the gut lumen/ feces of lupus patients.…”

Section: Introductionmentioning

confidence: 99%

Fecal immunoglobulin A (IgA) and its subclasses in systemic lupus erythematosus patients are nuclear antigen reactive and this feature correlates with gut permeability marker levels

Gudi

Kamen

Vasu

2022

Preprint

View full text Add to dashboard Cite

Objective: Systemic lupus erythematosus (SLE) is characterized by the production of anti-nuclear autoantibodies. Our preclinical studies showed a correlation between pro-inflammatory features of the gut mucosa and autoimmune progression in lupus. The current study was aimed at comparing stool samples of SLE patients and healthy controls (HC) for the gut permeability and inflammatory markers, and the abundance and nAg reactivity of immunoglobulin A (IgA) and its subclasses. Methods: The abundance of gut inflammation and permeability markers, Calprotectin and Zonulin, and IgA and IgA subclasses (IgA1 and IgA2) in cross-sectional stool samples from 21 SLE patients and 21 HC subjects were determined by quantitative ELISA. The nuclear-antigen (nAg) reactivities of fecal IgA and IgA-subclasses were determined by employing dsDNA and nucleohistone (NH) specific ELISA. Results: The abundances of Zonulin, total IgA, and IgA1- and IgA2- subclasses were observed to be significantly higher in the fecal samples of SLE patients compared to HCs. SLE patients also showed higher nAg reactivity titers of fecal IgA, IgA1 and IgA2. Importantly, dsDNA- and NH- reactive fecal IgA1:IgA2 ratios were higher in SLE patients. Furthermore, the abundance and nAg reactivity of fecal IgA, IgA1 particularly, showed strong correlation with the fecal Zonulin levels in SLE patients. Conclusion: Higher amounts of gut permeability protein and nAg-reactive IgA are produced in the intestine, likely in the proximal gut as indicated by the IgA1:IgA2 ratio, in SLE patients. These features of SLE patients, and perhaps at-risk subjects, could serve as biomarkers of systemic autoimmune activity. However, additional studies using longitudinal samples from first degree relatives are needed.

show abstract

Intestinal barrier dysfunction plays an integral role in arthritis pathology and can be targeted to ameliorate disease

Cited by 49 publications

References 68 publications

Gut dysbiosis in rheumatic diseases: A systematic review and meta-analysis of 92 observational studies

Gut dysbiosis in rheumatic diseases: A systematic review and meta-analysis of 92 observational studies

Gut-disc axis: A cause of intervertebral disc degeneration and low back pain?

Fecal immunoglobulin A (IgA) and its subclasses in systemic lupus erythematosus patients are nuclear antigen reactive and this feature correlates with gut permeability marker levels

Contact Info

Product

Resources

About