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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

Decreased diversity after antibiotic regimen in mice subjected to desiccating stress.(A) Schematic of experimental design. Mice were left non-stressed (NS) or subjected to desiccating stress (DS) for 5 or 10 days (DS5 and DS10) while drinking regular water. A separate group of mice received oral antibiotics (ABX: Ampicillin, Gentamicin, Metronidazole, Neomycin, Vancomycin) in water 14 days prior (baseline) and later were randomized to remain non-stressed (ABX + NS) or to be subjected to desiccating stress for 5 or days while still on ABX water (ABX + DS5 and ABX + DS10, respectively). Thick black arrow indicates duration of water treatment. (B) Number of observed operational taxonomic units (OTUs) and Shannon Diversity Index scores in non-stressed mice (NS, baseline) prior to exposure to desiccating stress (DS) with antibiotic cocktail (ABX) for 5 or 10 days (DS5 and DS10, respectively). ****P < 0.0001 compared to baseline group (Kruskall-Wallis test with FDR correction). (C) Principal coordinate analysis (PCoA) plot of unweighted UniFrac distances. Each symbol represents an individual sample from baseline and ABX mice subjected to DS for 5 and 10 days. PERMANOVA test, R2 = coefficient of determination. (D) Comparison of significant relative abundance of different genera among groups. Dotted line divides significant genera that decrease (left) or increase (right) in ABX + DS5 and ABX + DS10 compared to baseline. (Mean ± SEM) *P < 0.05; ****P < 0.0001 (Kruskall-Wallis test with FDR correction).
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f1: Decreased diversity after antibiotic regimen in mice subjected to desiccating stress.(A) Schematic of experimental design. Mice were left non-stressed (NS) or subjected to desiccating stress (DS) for 5 or 10 days (DS5 and DS10) while drinking regular water. A separate group of mice received oral antibiotics (ABX: Ampicillin, Gentamicin, Metronidazole, Neomycin, Vancomycin) in water 14 days prior (baseline) and later were randomized to remain non-stressed (ABX + NS) or to be subjected to desiccating stress for 5 or days while still on ABX water (ABX + DS5 and ABX + DS10, respectively). Thick black arrow indicates duration of water treatment. (B) Number of observed operational taxonomic units (OTUs) and Shannon Diversity Index scores in non-stressed mice (NS, baseline) prior to exposure to desiccating stress (DS) with antibiotic cocktail (ABX) for 5 or 10 days (DS5 and DS10, respectively). ****P < 0.0001 compared to baseline group (Kruskall-Wallis test with FDR correction). (C) Principal coordinate analysis (PCoA) plot of unweighted UniFrac distances. Each symbol represents an individual sample from baseline and ABX mice subjected to DS for 5 and 10 days. PERMANOVA test, R2 = coefficient of determination. (D) Comparison of significant relative abundance of different genera among groups. Dotted line divides significant genera that decrease (left) or increase (right) in ABX + DS5 and ABX + DS10 compared to baseline. (Mean ± SEM) *P < 0.05; ****P < 0.0001 (Kruskall-Wallis test with FDR correction).

Mentions: Our experimental design is presented in Fig. 1A. The effects of our standard DS model on the intestinal microbiome were evaluated by 16S rRNA gene sequencing of stools collected from the same group of mice prior to (non-stressed; NS) and after DS for 5 or 10 days. Mice drank regular water for the duration of the experiment. There was an increase in observed operational taxonomic units (OTUs, P = 0.013, data not shown) and Shannon diversity index at DS10 compared to NS control mice (P = 0.02; Kruskall-Wallis with false-discovery rate (FDR) correction, data not shown). Next we performed UniFrac analysis, which measures dissimilarity between microbial communities accounting for phylogenetic distance and permutational multivariate analysis of variance (PERMANOVA) using distance matrices which detects genetic differences in populations. Clustering was observed among these groups by unweighted UniFrac principal coordinate analysis (P = 0.006, PERMANOVA, data not shown). There was a small shift in the relative abundance of phyla in Proteobacteria in the DS group after 5 days of treatment (4.48 to 7.61%, DS5; P < 0.05; Kruskall-Wallis with FDR correction) and in DS10 compared to NS mice (4.48 vs. 11.94%, P < 0.05; Kruskall-Wallis with FDR correction; data not shown).


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)

Decreased diversity after antibiotic regimen in mice subjected to desiccating stress.(A) Schematic of experimental design. Mice were left non-stressed (NS) or subjected to desiccating stress (DS) for 5 or 10 days (DS5 and DS10) while drinking regular water. A separate group of mice received oral antibiotics (ABX: Ampicillin, Gentamicin, Metronidazole, Neomycin, Vancomycin) in water 14 days prior (baseline) and later were randomized to remain non-stressed (ABX + NS) or to be subjected to desiccating stress for 5 or days while still on ABX water (ABX + DS5 and ABX + DS10, respectively). Thick black arrow indicates duration of water treatment. (B) Number of observed operational taxonomic units (OTUs) and Shannon Diversity Index scores in non-stressed mice (NS, baseline) prior to exposure to desiccating stress (DS) with antibiotic cocktail (ABX) for 5 or 10 days (DS5 and DS10, respectively). ****P < 0.0001 compared to baseline group (Kruskall-Wallis test with FDR correction). (C) Principal coordinate analysis (PCoA) plot of unweighted UniFrac distances. Each symbol represents an individual sample from baseline and ABX mice subjected to DS for 5 and 10 days. PERMANOVA test, R2 = coefficient of determination. (D) Comparison of significant relative abundance of different genera among groups. Dotted line divides significant genera that decrease (left) or increase (right) in ABX + DS5 and ABX + DS10 compared to baseline. (Mean ± SEM) *P < 0.05; ****P < 0.0001 (Kruskall-Wallis test with FDR correction).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Decreased diversity after antibiotic regimen in mice subjected to desiccating stress.(A) Schematic of experimental design. Mice were left non-stressed (NS) or subjected to desiccating stress (DS) for 5 or 10 days (DS5 and DS10) while drinking regular water. A separate group of mice received oral antibiotics (ABX: Ampicillin, Gentamicin, Metronidazole, Neomycin, Vancomycin) in water 14 days prior (baseline) and later were randomized to remain non-stressed (ABX + NS) or to be subjected to desiccating stress for 5 or days while still on ABX water (ABX + DS5 and ABX + DS10, respectively). Thick black arrow indicates duration of water treatment. (B) Number of observed operational taxonomic units (OTUs) and Shannon Diversity Index scores in non-stressed mice (NS, baseline) prior to exposure to desiccating stress (DS) with antibiotic cocktail (ABX) for 5 or 10 days (DS5 and DS10, respectively). ****P < 0.0001 compared to baseline group (Kruskall-Wallis test with FDR correction). (C) Principal coordinate analysis (PCoA) plot of unweighted UniFrac distances. Each symbol represents an individual sample from baseline and ABX mice subjected to DS for 5 and 10 days. PERMANOVA test, R2 = coefficient of determination. (D) Comparison of significant relative abundance of different genera among groups. Dotted line divides significant genera that decrease (left) or increase (right) in ABX + DS5 and ABX + DS10 compared to baseline. (Mean ± SEM) *P < 0.05; ****P < 0.0001 (Kruskall-Wallis test with FDR correction).
Mentions: Our experimental design is presented in Fig. 1A. The effects of our standard DS model on the intestinal microbiome were evaluated by 16S rRNA gene sequencing of stools collected from the same group of mice prior to (non-stressed; NS) and after DS for 5 or 10 days. Mice drank regular water for the duration of the experiment. There was an increase in observed operational taxonomic units (OTUs, P = 0.013, data not shown) and Shannon diversity index at DS10 compared to NS control mice (P = 0.02; Kruskall-Wallis with false-discovery rate (FDR) correction, data not shown). Next we performed UniFrac analysis, which measures dissimilarity between microbial communities accounting for phylogenetic distance and permutational multivariate analysis of variance (PERMANOVA) using distance matrices which detects genetic differences in populations. Clustering was observed among these groups by unweighted UniFrac principal coordinate analysis (P = 0.006, PERMANOVA, data not shown). There was a small shift in the relative abundance of phyla in Proteobacteria in the DS group after 5 days of treatment (4.48 to 7.61%, DS5; P < 0.05; Kruskall-Wallis with FDR correction) and in DS10 compared to NS mice (4.48 vs. 11.94%, P < 0.05; Kruskall-Wallis with FDR correction; data not shown).

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