Sjögren-Like Lacrimal Keratoconjunctivitis in Germ-Free Mice

Wang, Changjun; Zaheer, Mahira; Bian, Fang; Quach, Darin; Swennes, Alton G.; Britton, Robert A.; Pflugfelder, Stephen C.; Paiva, Cintia S. de

doi:10.3390/ijms19020565

Cited by 71 publications

(82 citation statements)

References 80 publications

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“…The authors also reported that other organs, such as liver, lungs, heart, and spleen were smaller [10]. The GF mice in this protocol presented a phenotype consistent with previous publications [12][13][14]. They were lean with no discernable fat, presented a five-fold enlarged cecum relative to controls and exhibited slightly smaller organs; including smaller spleens, lungs, livers, and hearts ( Figure 3A-D).…”

Section: Expected Results and Discussionsupporting

confidence: 87%

Using a Model of Germ-Free Animals to Study the Impact of Gut Microbiome in Research: A Step by Step Sterility Setting and Management

Gabay

Vicenty

Smith

et al. 2020

MPs

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The particularly unique composition of the gut microbiota has the potential to influence the health or disease status of animal and human hosts. Altering the homeostasis of the host-bacteria could lead to changes in gut flora that result in disease or activation of a specific immunological response, which could explain the variations observed in patient responses to current therapies. A standardized model is crucial for studying the influence of the gut microbiota on therapeutic modalities. A step by step mouse model and sterility management system that compares a control strain of C57BL/6 mice to the established C57BL/6 germ-free (GF) strain has been developed. The GF BL/6 mouse phenotype is well established, and the anatomical differences between the GF and control mice were evident in this model. This method could be applied to research studies investigating the microbiome impact, the response to various therapies, or disease transfer via fecal transplants. A standardized sterility maintenance method is crucial in this context.

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Section: Expected Results and Discussionsupporting

confidence: 87%

Using a Model of Germ-Free Animals to Study the Impact of Gut Microbiome in Research: A Step by Step Sterility Setting and Management

Gabay

Vicenty

Smith

et al. 2020

MPs

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“…Similar findings have been seen in other mice models. Desiccating stress applied to the ocular surface with a fan in germ-free mice led to corneal staining and ocular surface inflammation, resulting in a worse DE phenotype compared to conventionally house mice [39]. In another experiment, antibiotics administered in addition to desiccating stress reduced Bacteroidetes and Firmicutes and increased Proteobacteria in the gut and concomitantly caused a more severe DE phenotype compared to desiccating stress alone [40].…”

Section: Discussionmentioning

confidence: 99%

Gut microbial dysbiosis in individuals with Sjögren’s syndrome

et al. 2020

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Background: Autoimmune diseases have been associated with changes in the gut microbiome. In this study, the gut microbiome was evaluated in individuals with dry eye and bacterial compositions were correlated to dry eye (DE) measures. We prospectively included 13 individuals with who met full criteria for Sjögren's (SDE) and 8 individuals with features of Sjögren's but who did not meet full criteria (NDE) for a total of 21 cases as compared to 21 healthy controls. Stool was analyzed by 16S pyrosequencing, and associations between bacterial classes and DE symptoms and signs were examined.Results: Results showed that Firmicutes was the dominant phylum in the gut, comprising 40-60% of all phyla. On a phyla level, subjects with DE (SDE and NDE) had depletion of Firmicutes (1.1-fold) and an expansion of Proteobacteria (3.0-fold), Actinobacteria (1.7-fold), and Bacteroidetes (1.3-fold) compared to controls. Shannon's diversity index showed no differences between groups with respect to the numbers of different operational taxonomic units (OTUs) encountered (diversity) and the instances these unique OTUs were sampled (evenness). On the other hand, Faith's phylogenetic diversity showed increased diversity in cases vs controls, which reached significance when comparing SDE and controls (13.57 ± 0.89 and 10.96 ± 0.76, p = 0.02). Using Principle Co-ordinate Analysis, qualitative differences in microbial composition were noted with differential clustering of cases and controls. Dimensionality reduction and clustering of complex microbial data further showed differences between the three groups, with regard to microbial composition, association and clustering. Finally, differences in certain classes of bacteria were associated with DE symptoms and signs. Conclusions:In conclusion, individuals with DE had gut microbiome alterations as compared to healthy controls. Certain classes of bacteria were associated with DE measures.

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“…Desiccating stress applied to the ocular surface with a fan in germ-free mice led to corneal staining and ocular surface inflammation, resulting in a worse DE phenotype compared to conventionally house mice. 44 In another experiment, antibiotics administered in addition to desiccating stress reduced Bacteroidetes and Firmicutes and increased Proteobacteria in the gut and concomitantly caused a more severe DE phenotype compared to desiccating stress alone. 45 These experiments reinforce the idea of a gut-eye axis and highlight the possibility of gut microbiome modulation and a therapeutic approach in DE.…”

Section: Discussionmentioning

confidence: 98%

Gut microbial dysbiosis in individuals with Sjögren’s disease

Méndez

Watane

Farhangi

et al. 2019

Preprint

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Purpose: To evaluate the gut microbiome in individuals with Sjögrens and correlate bacterial profiles to dry eye (DE) measures.Methods: Prospective case series of individuals with confirmed (n=13) and unconfirmed (n=8) Sjögrens (n=21; cases) as compared to healthy controls (n=10). Stool was analyzed by 16S pyrosequencing and associations between bacterial classes and DE symptoms and signs were examined. Results:Firmicutes was the dominant phylum in the gut, comprising 40-60% of all phyla. On a phyla level, subjects with Sjögrens (confirmed and unconfirmed) had depletion of Firmicutes (1.1-fold) and an expansion of Proteobacteria (3.0-fold), Actinobacteria (1.7-fold), and Bacteroidetes (1.3-fold) compared to controls. Shannon's diversity index showed no differences between groups with respect to the numbers of different OTUs encountered (diversity) and the instances these unique OTUs were sampled (evenness). On the other hand, Faith's phylogenetic diversity showed increased diversity in cases vs controls, which reached significance when comparing confirmed Sjögrens and controls (13.57 ± 0.89 and 10.96 ± 0.76, p=0.02). Using Principle Co-ordinate Analysis, qualitative differences in microbial composition were noted with differential clustering of cases and controls. Dimensionality reduction and clustering of complex microbial data further showed differences between the three groups, with regard to microbial composition, association and clustering. Finally, differences in certain classes of bacteria correlated with DE symptoms and signs.Conclusions: Individuals with Sjögrens have gut microbiome alterations as compared to healthy controls. Certain classes of bacteria were associated with DE measures.≤ 5 in either eye; or (3) an autoimmune disease (e.g. rheumatoid arthritis, psoriasis). The Miami VA and University of Miami Institutional Review Boards (IRB) approved the prospective evaluation of patients. Informed consent was obtained from all subjects and the study was adherent with the principles of the Declaration of Helsinki.Clinical metrics: Demographic information for each participant was collected including age, gender, race, ethnicity, past ocular and medical history and current medications. DE symptoms:Participants completed two standardized DE symptoms questionnaires: the Dry Eye Questionnaire 5 (DEQ5) 18 (score 0-22) and the Ocular Surface Disease Index (OSDI) 19 (score 0-100). DE signs:Participants underwent a complete ocular surface exam of both eyes in the following order: 1) Ocular surface inflammation via matrix metalloproteinase (MMP) 9 levels (Inflammadry, Quantel, San Diego, CA) 20 graded based on intensity of pink line (0 = no line, 1 = faint line, 2 = pink line, 3 = intense pink line). 2) Tear breakup time (TBUT) using fluorescein stain measured three times in each eye and averaged. 3) Corneal staining using fluorescein stain evaluated using the National Eye Institute (NEI) scoring scale which assesses 5 areas of the cornea on a 0-3 scale with a total score generated by summing the 5 section scores...

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Sjögren-Like Lacrimal Keratoconjunctivitis in Germ-Free Mice

Cited by 71 publications

References 80 publications

Using a Model of Germ-Free Animals to Study the Impact of Gut Microbiome in Research: A Step by Step Sterility Setting and Management

Using a Model of Germ-Free Animals to Study the Impact of Gut Microbiome in Research: A Step by Step Sterility Setting and Management

Gut microbial dysbiosis in individuals with Sjögren’s syndrome

Gut microbial dysbiosis in individuals with Sjögren’s disease

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