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Altered Mucosal Microbiome Diversity and Disease Severity in Sjögren Syndrome.

de Paiva CS, Jones DB, Stern ME, Bian F, Moore QL, Corbiere S, Streckfus CF, Hutchinson DS, Ajami NJ, Petrosino JF, Pflugfelder SC - Sci Rep (2016)

Bottom Line: ABX + DS mice had a significantly worse dry eye phenotype compared to controls, a decrease in Clostridium and an increase in Enterobacter, Escherichia/Shigella, and Pseudomonas in stool after ABX + DS for 10 days.Goblet cell density was significantly lower in ABX treated groups compared to controls.Stool from SS subjects had greater relative abundances of Pseudobutyrivibrio, Escherichia/Shigella, Blautia, and Streptococcus, while relative abundance of Bacteroides, Parabacteroides, Faecalibacterium, and Prevotella was reduced compared to controls.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.

ABSTRACT
There is mounting evidence that the microbiome has potent immunoregulatory functions. We assessed the effects of intestinal dysbiosis in a model of Sjögren syndrome (SS) by subjecting mice to desiccating stress (DS) and antibiotics (ABX). We characterized the conjunctival, tongue and fecal microbiome profiles of patients with SS. Severity of ocular surface and systemic disease was graded. 16S ribosomal RNA gene sequencing characterized the microbiota. ABX + DS mice had a significantly worse dry eye phenotype compared to controls, a decrease in Clostridium and an increase in Enterobacter, Escherichia/Shigella, and Pseudomonas in stool after ABX + DS for 10 days. Goblet cell density was significantly lower in ABX treated groups compared to controls. Stool from SS subjects had greater relative abundances of Pseudobutyrivibrio, Escherichia/Shigella, Blautia, and Streptococcus, while relative abundance of Bacteroides, Parabacteroides, Faecalibacterium, and Prevotella was reduced compared to controls. The severity of SS ocular and systemic disease was inversely correlated with microbial diversity. These findings suggest that SS is marked by a dysbiotic intestinal microbiome driven by low relative abundance of commensal bacteria and high relative abundance of potentially pathogenic genera that is associated with worse ocular mucosal disease in a mouse model of SS and in SS patients.

No MeSH data available.


Related in: MedlinePlus

Gut dysbiosis worsens response to desiccating stress and increases production of T-cell related cytokines in conjunctival epithelium.(A–C) Goblet cell density (A), CD4+T cell infiltration (B) and corneal barrier function measured by uptake of Oregon-Green Dextran (OGD, C) in mice prior to (baseline, NS) and after exposure to desiccating stress with and without antibiotic cocktail (ABX) for 5 or 10 days (DS5 and DS10, respectively). *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001 water vs. ABX comparisons; Kruskall-Wallis followed by Sidak’s multi-comparisons test. (D). Relative fold of expression of IL-17, IFN-γ, IL-13, Foxa2, IL-13/IFN-γ ratio and Integrin alpha 2 (Itga2, CD49b) in conjunctiva from mice prior to (non-stressed, NS) and after exposure to desiccating stress with and without antibiotic cocktail (ABX) for 5 or 10 days (DS5 and DS10, respectively). Data are presented as mean ± SEM of a representative experiment containing 3-4 individual samples/group. Experiment was repeated once with similar results. *p < 0.05; **p < 0.01, ***p < 0.001; ****p < 0.0001 water vs. ABX at each time point, calculated by Kruskall-Wallis followed by Sidak’s multi-comparisons test.
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f2: Gut dysbiosis worsens response to desiccating stress and increases production of T-cell related cytokines in conjunctival epithelium.(A–C) Goblet cell density (A), CD4+T cell infiltration (B) and corneal barrier function measured by uptake of Oregon-Green Dextran (OGD, C) in mice prior to (baseline, NS) and after exposure to desiccating stress with and without antibiotic cocktail (ABX) for 5 or 10 days (DS5 and DS10, respectively). *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001 water vs. ABX comparisons; Kruskall-Wallis followed by Sidak’s multi-comparisons test. (D). Relative fold of expression of IL-17, IFN-γ, IL-13, Foxa2, IL-13/IFN-γ ratio and Integrin alpha 2 (Itga2, CD49b) in conjunctiva from mice prior to (non-stressed, NS) and after exposure to desiccating stress with and without antibiotic cocktail (ABX) for 5 or 10 days (DS5 and DS10, respectively). Data are presented as mean ± SEM of a representative experiment containing 3-4 individual samples/group. Experiment was repeated once with similar results. *p < 0.05; **p < 0.01, ***p < 0.001; ****p < 0.0001 water vs. ABX at each time point, calculated by Kruskall-Wallis followed by Sidak’s multi-comparisons test.

Mentions: Phenotypically, mice subjected to ABX + DS had greater goblet cell (GC) loss (ABX + DS5 and ABX + DS10, P < 0.001 for both, Kruskall-Wallis with Sidak’s test), increased number of CD4+T cells infiltrating the conjunctival epithelium (ABX + DS5 and ABX + DS10, P < 0.001 for both time points; Kruskall-Wallis with Sidak’s test), and greater corneal barrier disruption (ABX + DS5, Fig. 2A–C, P < 0.05; Kruskall-Wallis with Sidak’s test) than mice subjected to DS alone.


Altered Mucosal Microbiome Diversity and Disease Severity in Sjögren Syndrome.

de Paiva CS, Jones DB, Stern ME, Bian F, Moore QL, Corbiere S, Streckfus CF, Hutchinson DS, Ajami NJ, Petrosino JF, Pflugfelder SC - Sci Rep (2016)

Gut dysbiosis worsens response to desiccating stress and increases production of T-cell related cytokines in conjunctival epithelium.(A–C) Goblet cell density (A), CD4+T cell infiltration (B) and corneal barrier function measured by uptake of Oregon-Green Dextran (OGD, C) in mice prior to (baseline, NS) and after exposure to desiccating stress with and without antibiotic cocktail (ABX) for 5 or 10 days (DS5 and DS10, respectively). *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001 water vs. ABX comparisons; Kruskall-Wallis followed by Sidak’s multi-comparisons test. (D). Relative fold of expression of IL-17, IFN-γ, IL-13, Foxa2, IL-13/IFN-γ ratio and Integrin alpha 2 (Itga2, CD49b) in conjunctiva from mice prior to (non-stressed, NS) and after exposure to desiccating stress with and without antibiotic cocktail (ABX) for 5 or 10 days (DS5 and DS10, respectively). Data are presented as mean ± SEM of a representative experiment containing 3-4 individual samples/group. Experiment was repeated once with similar results. *p < 0.05; **p < 0.01, ***p < 0.001; ****p < 0.0001 water vs. ABX at each time point, calculated by Kruskall-Wallis followed by Sidak’s multi-comparisons test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4834578&req=5

f2: Gut dysbiosis worsens response to desiccating stress and increases production of T-cell related cytokines in conjunctival epithelium.(A–C) Goblet cell density (A), CD4+T cell infiltration (B) and corneal barrier function measured by uptake of Oregon-Green Dextran (OGD, C) in mice prior to (baseline, NS) and after exposure to desiccating stress with and without antibiotic cocktail (ABX) for 5 or 10 days (DS5 and DS10, respectively). *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001 water vs. ABX comparisons; Kruskall-Wallis followed by Sidak’s multi-comparisons test. (D). Relative fold of expression of IL-17, IFN-γ, IL-13, Foxa2, IL-13/IFN-γ ratio and Integrin alpha 2 (Itga2, CD49b) in conjunctiva from mice prior to (non-stressed, NS) and after exposure to desiccating stress with and without antibiotic cocktail (ABX) for 5 or 10 days (DS5 and DS10, respectively). Data are presented as mean ± SEM of a representative experiment containing 3-4 individual samples/group. Experiment was repeated once with similar results. *p < 0.05; **p < 0.01, ***p < 0.001; ****p < 0.0001 water vs. ABX at each time point, calculated by Kruskall-Wallis followed by Sidak’s multi-comparisons test.
Mentions: Phenotypically, mice subjected to ABX + DS had greater goblet cell (GC) loss (ABX + DS5 and ABX + DS10, P < 0.001 for both, Kruskall-Wallis with Sidak’s test), increased number of CD4+T cells infiltrating the conjunctival epithelium (ABX + DS5 and ABX + DS10, P < 0.001 for both time points; Kruskall-Wallis with Sidak’s test), and greater corneal barrier disruption (ABX + DS5, Fig. 2A–C, P < 0.05; Kruskall-Wallis with Sidak’s test) than mice subjected to DS alone.

Bottom Line: ABX + DS mice had a significantly worse dry eye phenotype compared to controls, a decrease in Clostridium and an increase in Enterobacter, Escherichia/Shigella, and Pseudomonas in stool after ABX + DS for 10 days.Goblet cell density was significantly lower in ABX treated groups compared to controls.Stool from SS subjects had greater relative abundances of Pseudobutyrivibrio, Escherichia/Shigella, Blautia, and Streptococcus, while relative abundance of Bacteroides, Parabacteroides, Faecalibacterium, and Prevotella was reduced compared to controls.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.

ABSTRACT
There is mounting evidence that the microbiome has potent immunoregulatory functions. We assessed the effects of intestinal dysbiosis in a model of Sjögren syndrome (SS) by subjecting mice to desiccating stress (DS) and antibiotics (ABX). We characterized the conjunctival, tongue and fecal microbiome profiles of patients with SS. Severity of ocular surface and systemic disease was graded. 16S ribosomal RNA gene sequencing characterized the microbiota. ABX + DS mice had a significantly worse dry eye phenotype compared to controls, a decrease in Clostridium and an increase in Enterobacter, Escherichia/Shigella, and Pseudomonas in stool after ABX + DS for 10 days. Goblet cell density was significantly lower in ABX treated groups compared to controls. Stool from SS subjects had greater relative abundances of Pseudobutyrivibrio, Escherichia/Shigella, Blautia, and Streptococcus, while relative abundance of Bacteroides, Parabacteroides, Faecalibacterium, and Prevotella was reduced compared to controls. The severity of SS ocular and systemic disease was inversely correlated with microbial diversity. These findings suggest that SS is marked by a dysbiotic intestinal microbiome driven by low relative abundance of commensal bacteria and high relative abundance of potentially pathogenic genera that is associated with worse ocular mucosal disease in a mouse model of SS and in SS patients.

No MeSH data available.


Related in: MedlinePlus