Gut microbiota and derived metabolomic profiling in glaucoma with progressive neurodegeneration

Study information

Reviewed Marked as Reviewed by KateRasheed on 2025-8-18

study design

laboratory experiment

Citation

PMID PubMed identifier for scientific articles.

36034713

DOI Digital object identifier for electronic documents.

10.3389/fcimb.2022.968992

URI Uniform resource identifier for web resources.

Authors

Zhang Y, Zhou X, Lu Y

Journal

Frontiers in cellular and infection microbiology

Year

2022

Keywords:

Glaucoma, glutathione, gut microbiota, microbial metabolite, retinal ganglion cell (RGC)

Glaucoma is a multifactorial, neurodegenerative disorder characterized by the loss of retinal ganglion cells (RGCs). Crosstalk between the gut microbiota and host is involved in the progression of many neurodegenerative diseases, although little is known about its role in glaucoma. To investigated the alterations of the gut microbiota and derived metabolites in glaucomatous rats, and the interaction with RGCs, we performed 16S rRNA (V1-V9) sequencing and untargeted metabolomic analyses. The microbial composition differed significantly between the two groups, and the diversity of cecal bacteria was dramatically reduced in glaucomatous rats. The Firmicutes/Bacteroidetes (F/B) ratio, Verrucomicrobia phylum, and some bacterial genera (Romboutsia, Akkermansia, and Bacteroides) were dramatically increased in the glaucomatous rat model compared with the control, which showed negative correlation with RGCs. Untargeted metabolomic analysis identified 284 differentially expressed metabolites, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed considerable enrichment mainly in bile secretion pathways. The relationships among the metabolites enriched in the bile secretion pathway, differentially expressed cecal microbiota, and RGCs were investigated, and glutathione (GSH) was found to be negatively correlated with Bacteroides and F/B and positively correlated with RGCs. Reduced GSH level in the blood of glaucoma rats is further established, and was negatively correlated with Romboutsia and the F/B ratio and positively correlated with RGCs. This finding suggests the potential role of the gut microbiota and derived metabolites in glaucoma, and GSH, a major antioxidant metabolite, was related to their effects, indicating the potential for the development of gut microbiota-targeted interventions for glaucoma.

Experiment 1

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Reviewed Marked as Reviewed by KateRasheed on 2025-8-18

Curated date: 2025/07/31

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Subjects

Location of subjects: China

Host species Species from which microbiome was sampled. Contact us to have more species added.: Rattus norvegicus

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Caecum Blind intestine,Blindgut,Caeca,Caecum,Ceca,Cecum,Intestinum caecum,Intestinum crassum caecum,Intestinum crassum cecum,caecum

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Glaucoma glaucoma,glaucoma (disease),Glaucoma (disorder),Glaucoma associated with other ocular disorders,Glaucoma associated with other ocular disorders (disorder),Glaucoma associated with other ocular disorders NOS,Glaucoma associated with other ocular disorders NOS (disorder),GLAUCOMA NEC,Glaucoma NOS,Glaucoma NOS (disorder),Glaucoma, NOS,Glaucomas,Other specified forms of glaucoma,Other specified forms of glaucoma (disorder),Other specified glaucoma,Other specified glaucoma NOS,Other specified glaucoma NOS (disorder),Unspecified glaucoma,Glaucoma

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Control

Group 1 name Corresponds to the case (exposed) group for case-control studies: Glaucoma

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Male wistar rats in the glaucomatous group

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V1-V9

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: PacBio Vega (VS)/Revio (RS)/Sequel II

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 2

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased

Chao1 Abundance-based estimator of species richness: unchanged

Signature 1

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Reviewed Marked as Reviewed by KateRasheed on 2025-8-18

Curated date: 2025/07/31

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 3A, B

Description: Significant differentially abundant bacterial taxa between glaucoma and control rats using LEfSe analysis

Abundance in Group 1: increased abundance in Glaucoma

NCBI	Quality Control	Links
Akkermansia
Akkermansiaceae
Alistipes shahii
Alphaproteobacteria
Anaerofustis
Bacteroidaceae
Bacteroides
Eubacteriaceae
Peptostreptococcaceae
Romboutsia
Turicibacter
Verrucomicrobiales
Verrucomicrobiia
Verrucomicrobiota
Helicobacter ganmani
Bacteroides fragilis
Alistipes
Bacteroides intestinalis
Rikenellaceae
Muribaculum
Campylobacterales
Helicobacteraceae
Helicobacter

Revision editor(s): Anne-mariesharp

Signature 2

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Reviewed Marked as Reviewed by KateRasheed on 2025-8-18

Curated date: 2025/07/31

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 3A, B

Description: Significant differentially abundant bacterial taxa between glaucoma and control rats using LEfSe analysis

Abundance in Group 1: decreased abundance in Glaucoma

NCBI	Quality Control	Links
Alloprevotella
Anaeroplasma
Anaeroplasmataceae
Anaeroplasmatales
Candidatus Melainabacteria
Clostridia bacterium UC5.1-1D1
Parabacteroides
Parabacteroides distasonis
Tannerellaceae
bacterium enrichment culture clone LA92
Limosilactobacillus reuteri
Ligilactobacillus animalis
Lactobacillus johnsonii
Lachnospiraceae