Alterations in the gut bacterial microbiome in people with type 2 diabetes mellitus and diabetic retinopathy

Das, Taraprasad; Jayasudha, Rajagopalaboopathi; Chakravarthy, SamaKalyana; Prashanthi, Gumpili Sai; Bhargava, Archana; Tyagi, Mudit; Rani, Padmaja Kumari; Pappuru, Rajeev Reddy; Sharma, Savitri; Shivaji, Sisinthy

doi:10.1038/s41598-021-82538-0

Cited by 114 publications

(151 citation statements)

References 86 publications

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“…Recent studies demonstrated the alterations and possible application prospects of the gut microbiome in patients with other ocular neovascular diseases, such as DR (Das et al, 2021;Huang et al, 2021) and retinopathy of prematurity (Skondra et al, 2020). Das et al (2021) recognized a reduction in anti-inflammatory, probiotic and other bacteria that could be pathogenic in the microbiomes of patients with both diabetes mellitus and DR, compared to the healthy controls, and the changes observed in DR patients were more pronounced. Huang et al (2021) indicated the potential use of gut microbiota as a biomarker of DR, which could be helpful for diagnosis in clinical applications.…”

Section: Discussionmentioning

confidence: 99%

Altered Fecal Microbiome and Metabolome in a Mouse Model of Choroidal Neovascularization

Cai

Huang

et al. 2021

Front. Microbiol.

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PurposeChoroidal neovascularization (CNV) is the defining feature of neovascular age-related macular degeneration (nAMD). Gut microbiota might be deeply involved in the pathogenesis of nAMD. This study aimed to reveal the roles of the gut microbiome and fecal metabolome in a mouse model of laser-induced CNV.MethodsThe feces of C57BL/6J mice with or without laser-induced CNV were collected. Multi-omics analyses, including 16S rRNA gene sequencing and untargeted metabolomics, were conducted to analyze the changes in the gut microbial composition and the fecal metabolomic profiles in CNV mice.ResultsThe gut microbiota was significantly altered in CNV mice. The abundance of Candidatus_Saccharimonas was significantly upregulated in the feces of CNV mice, while 16 genera, including Prevotellaceae_NK3B31_group, Candidatus_Soleaferrea, and Truepera, were significantly more abundant in the controls than in the CNV group. Fecal metabolomics identified 73 altered metabolites (including 52 strongly significantly altered metabolites) in CNV mice compared to control mice. Correlation analysis indicated significant correlations between the altered fecal metabolites and gut microbiota genera, such as Lachnospiraceae_UCG-001 and Candidatus_Saccharimonas. Moreover, KEGG analysis revealed six pathways associated with these altered metabolites, such as the ABC transporter, primary bile acid biosynthesis and steroid hormone biosynthesis pathways.ConclusionThe study identified an altered fecal microbiome and metabolome in a CNV mouse model. The altered microbes, metabolites and the involved pathways might be associated with the pathogenesis of nAMD.

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Section: Discussionmentioning

confidence: 99%

Altered Fecal Microbiome and Metabolome in a Mouse Model of Choroidal Neovascularization

Cai

Huang

et al. 2021

Front. Microbiol.

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“…Moreover, resistant bacteria could be targeted specifically, clearing them from the infection and leaving antibiotic susceptible bacteria that can be eliminated by standard antibiotic treatments 17 . In addition, the technique could also be used for targeted microbiome engineering, highlighting the potential of CRISPR-Cas based medicine to not only treat infectious diseases but also multiple microbiome-related conditions such as diabetes 18 , obesity 19 and cancer 20 , 21 .…”

Section: Introductionmentioning

confidence: 99%

Bacterial resistance to CRISPR-Cas antimicrobials

Uribe

Rathmer

Jahn

et al. 2021

Sci Rep

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In the age of antibiotic resistance and precise microbiome engineering, CRISPR-Cas antimicrobials promise to have a substantial impact on the way we treat diseases in the future. However, the efficacy of these antimicrobials and their mechanisms of resistance remain to be elucidated. We systematically investigated how a target E. coli strain can escape killing by episomally-encoded CRISPR-Cas9 antimicrobials. Using Cas9 from Streptococcus pyogenes (SpCas9) we studied the killing efficiency and resistance mutation rate towards CRISPR-Cas9 antimicrobials and elucidated the underlying genetic alterations. We find that killing efficiency is not correlated with the number of cutting sites or the type of target. While the number of targets did not significantly affect efficiency of killing, it did reduce the emergence of chromosomal mutations conferring resistance. The most frequent target of resistance mutations was the plasmid-encoded SpCas9 that was inactivated by bacterial genome rearrangements involving translocation of mobile genetic elements such as insertion elements. This resistance mechanism can be overcome by re-introduction of an intact copy of SpCas9. The work presented here provides a guide to design strategies that reduce resistance and improve the activity of CRISPR-Cas antimicrobials.

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“…Genomic DNA was extracted from ∼150 mg of homogenized fecal pellets, and the quality of DNA was checked as described earlier. 13 – 17 …”

Section: Methodsmentioning

confidence: 99%

“…SILVA 138 SSU ( https://www.arb-silva.de/documentation/release-138/ ) was used as the reference OTU database to identify bacteria at 97% identity, and the assignment of taxonomy was made as described in our earlier studies. 17 , 25 Sparse OTUs (<0.001% of the total HQ reads) were not considered.…”

Section: Methodsmentioning

confidence: 99%

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Dysbiosis in the Gut Microbiome in Streptozotocin-Induced Diabetes Rats and Follow-Up During Retinal Changes

Padakandla

Das

Prashanthi

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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Purpose To analyze the gut bacterial microbiome of streptozotocin-induced diabetic rats and rats with retinal changes. Methods Induction of diabetes was confirmed by an increase in blood sugar (>150 mg/dL), and the progression of diabetes with retinal changes was assessed by histology and immunohistochemistry of retinal sections. Microbiomes were generated using fecal DNA, and the V3–V4 amplicons were sequenced and analyzed by QIIME and R. Results Dysbiosis in the gut microbiome of diabetic rats and diabetic rats with retinal changes was observed at the phylum and genus levels compared with the control rats. Heat-map analysis based on the differentially abundant genera indicated that the microbiomes of controls and diabetic rats separated into two distinct clusters. The majority of the microbiomes in diabetic rats with retinal changes also formed a distinct cluster from the control rats. β-diversity analysis separated the microbiome of control rats from the microbiome of diabetic rats and diabetic rats with retinal changes, but the microbiomes of diabetic rats and diabetic rats with retinal changes showed an overlap. Functional analysis indicated that the enhanced inflammation in diabetic rats showing retinal changes could be ascribed to a decrease in anti-inflammatory bacteria and an increase in pathogenic and proinflammatory bacteria. Conclusions This study showed that the gut bacterial microbiome in diabetic rats with retinal changes was different compared with control rats. The results could help develop novel therapeutics for diabetics and diabetic individuals with retinal changes.

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Alterations in the gut bacterial microbiome in people with type 2 diabetes mellitus and diabetic retinopathy

Cited by 114 publications

References 86 publications

Altered Fecal Microbiome and Metabolome in a Mouse Model of Choroidal Neovascularization

Altered Fecal Microbiome and Metabolome in a Mouse Model of Choroidal Neovascularization

Bacterial resistance to CRISPR-Cas antimicrobials

Dysbiosis in the Gut Microbiome in Streptozotocin-Induced Diabetes Rats and Follow-Up During Retinal Changes

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