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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

Human stool microbiome in SS.(A) Comparison of all significant shifts in the abundance of genera between control subjects and SS patients (Mean ± SEM). Dotted line divides significant genera that decrease (top) or increase (bottom) in SS compared to controls. (B) Inverse Pearson’s correlation of combined severity index and number of intestinal OTUs, R = coefficient of correlation (C). Ocular severity graded (0–4) Dry Eye Workshop (DEWS) criteria, systemic severity graded (0–33) using unweighted 12-domain ESSDAI (European League against rheumatism (EULAR) Sjögren syndrome disease activity index) and combined ocular and systemic severity (sum of ocular and systemic severity scores). NS = non-significant. *p < 0.05; **p < 0.01, ***p < 0.001; ****p < 0.0001 Mann-Whitney test. NP: not performed.
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f3: Human stool microbiome in SS.(A) Comparison of all significant shifts in the abundance of genera between control subjects and SS patients (Mean ± SEM). Dotted line divides significant genera that decrease (top) or increase (bottom) in SS compared to controls. (B) Inverse Pearson’s correlation of combined severity index and number of intestinal OTUs, R = coefficient of correlation (C). Ocular severity graded (0–4) Dry Eye Workshop (DEWS) criteria, systemic severity graded (0–33) using unweighted 12-domain ESSDAI (European League against rheumatism (EULAR) Sjögren syndrome disease activity index) and combined ocular and systemic severity (sum of ocular and systemic severity scores). NS = non-significant. *p < 0.05; **p < 0.01, ***p < 0.001; ****p < 0.0001 Mann-Whitney test. NP: not performed.

Mentions: Stool sequences from ten SS patients were compared to publicly available HMP (Human Microbiome Project) data46. The HMP samples were taken from a well-characterized mixed gender healthy control group in which no differences in abundance or diversity of the stool microbiome was found between sexes47. The genera with significant between group differences after Mann-Whitney test are presented in Fig. 3A. We observed a greater abundance of Pseudobutyrivibrio, Escherichia/Shigella, Blautia, and Streptococcus, while Bacteroides, Parabacteroides, Faecalibacterium, and Prevotella were significantly reduced in stool samples from SS individuals (Mann-Whitney test, individual P values are noted in Fig. 3A). There was a 50% decrease in relative abundance of OTUs classified by the NCBI database (≥90% identity) to the high butyrate producer Faecalibacterium prausnitzii by NCBI mapping.


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)

Human stool microbiome in SS.(A) Comparison of all significant shifts in the abundance of genera between control subjects and SS patients (Mean ± SEM). Dotted line divides significant genera that decrease (top) or increase (bottom) in SS compared to controls. (B) Inverse Pearson’s correlation of combined severity index and number of intestinal OTUs, R = coefficient of correlation (C). Ocular severity graded (0–4) Dry Eye Workshop (DEWS) criteria, systemic severity graded (0–33) using unweighted 12-domain ESSDAI (European League against rheumatism (EULAR) Sjögren syndrome disease activity index) and combined ocular and systemic severity (sum of ocular and systemic severity scores). NS = non-significant. *p < 0.05; **p < 0.01, ***p < 0.001; ****p < 0.0001 Mann-Whitney test. NP: not performed.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Human stool microbiome in SS.(A) Comparison of all significant shifts in the abundance of genera between control subjects and SS patients (Mean ± SEM). Dotted line divides significant genera that decrease (top) or increase (bottom) in SS compared to controls. (B) Inverse Pearson’s correlation of combined severity index and number of intestinal OTUs, R = coefficient of correlation (C). Ocular severity graded (0–4) Dry Eye Workshop (DEWS) criteria, systemic severity graded (0–33) using unweighted 12-domain ESSDAI (European League against rheumatism (EULAR) Sjögren syndrome disease activity index) and combined ocular and systemic severity (sum of ocular and systemic severity scores). NS = non-significant. *p < 0.05; **p < 0.01, ***p < 0.001; ****p < 0.0001 Mann-Whitney test. NP: not performed.
Mentions: Stool sequences from ten SS patients were compared to publicly available HMP (Human Microbiome Project) data46. The HMP samples were taken from a well-characterized mixed gender healthy control group in which no differences in abundance or diversity of the stool microbiome was found between sexes47. The genera with significant between group differences after Mann-Whitney test are presented in Fig. 3A. We observed a greater abundance of Pseudobutyrivibrio, Escherichia/Shigella, Blautia, and Streptococcus, while Bacteroides, Parabacteroides, Faecalibacterium, and Prevotella were significantly reduced in stool samples from SS individuals (Mann-Whitney test, individual P values are noted in Fig. 3A). There was a 50% decrease in relative abundance of OTUs classified by the NCBI database (≥90% identity) to the high butyrate producer Faecalibacterium prausnitzii by NCBI mapping.

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