The gut microbiota and diabetic nephropathy: an observational study review and bidirectional Mendelian randomization study

Earlier studies have implicated a crucial link between diabetic nephropathy (DN) and the gut microbiota (GM) by considering the gut-kidney axis; however, the specific cause-and-effect connections between these processes remain unclear. To compare changes in the GM between DN patients and control sub...

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Published inCurrent controlled trials in cardiovascular medicine Vol. 26; no. 1; pp. 101 - 25
Main Authors Han, Yi Zhen, Wang, Yang Zhi Yuan, Zhu, Xing Yu, Du, Bo Xuan, Wang, Yao Xian, Zhang, Xue Qin, Jia, Jia Meng, Liu, Wei Jing, Zheng, Hui Juan
Format Journal Article
LanguageEnglish
Published England BioMed Central Ltd 24.03.2025
BioMed Central
BMC
Subjects
Analysis
Confounding (Statistics)
Diabetes
Diabetic nephropathies
Diabetic Nephropathies - genetics
Diabetic Nephropathies - microbiology
Diabetic nephropathy
Ethics
Gastrointestinal Microbiome - genetics
Genetically modified organisms
Genome-Wide Association Study
Genomes
Genomics
Gut microbiota
Gut–kidney axis
Humans
Kidney diseases
Mapping
Mendelian randomization
Mendelian Randomization Analysis
Metabolism
Microbiota
Microbiota (Symbiotic organisms)
Observational studies
Observational Studies as Topic
Review
Sample size
Variables
Gut microbiota
Diabetic nephropathy
Mendelian randomization
Gut–kidney axis
Observational studies
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Abstract Earlier studies have implicated a crucial link between diabetic nephropathy (DN) and the gut microbiota (GM) by considering the gut-kidney axis; however, the specific cause-and-effect connections between these processes remain unclear. To compare changes in the GM between DN patients and control subjects, a review of observational studies was performed. The examination focused on the phylum, family, genus, and species/genus categories. To delve deeper into the cause-effect relationship, instrumental variables for 211 GM taxa (9 phyla, 16 classes, 20 orders, 35 families, and 131 genera), which were eligible for the mbQTL (microbial quantitative trait locus) mapping analysis, were collected from the Genome Wide Association Study (GWAS). A Mendelian randomization investigation was then conducted to gauge their impact on DN susceptibility using data from the European Bioinformatics Institute (EBI) and the FinnGen consortium. The European Bioinformatics Institute data included 1032 DN patients and 451,248 controls, while the FinnGen consortium data consisted of 3283 DN patients and 210,463 controls. Two-sample Mendelian randomization (TSMR) was utilized to determine the link between the GM and DN. The primary method for analysis was the inverse variance weighted (IVW) approach. Moreover, a reverse Mendelian randomization analysis was carried out, and the findings were validated through sensitivity assessments. This review examined 11 observational studies that satisfied the inclusion and exclusion criteria. There was a significant difference in the abundance of 144 GM taxa between DN patients and controls. By employing the MR technique, 13 bacteria were pinpointed as having a causal link to DN (including 3 unknown GM taxa). Even after Bonferroni correction, the protective impact of the phylum Proteobacteria and genus Dialister (Sequeira et al. Nat Microbiol. 5:304-313, 2020; Liu et al. EBioMedicine. 90:104527, 2023) and the harmful impact of the genus Akkermansia, family Verrucomicrobiaceae, order Verrucomicrobia and class Verrucomicrobiae on DN remained significant. No noticeable heterogeneity or horizontal pleiotropy was detected in the instrumental variables (IVs). However, reverse MR investigations have failed to reveal any substantial causal relationship between DN and the GM. Differences in the GM among DN patients and healthy controls are explored in observational studies. We verified the possible connection between certain genetically modified genera and DN, thereby emphasizing the connection between the "gut-kidney" axis and new insights into the GM's role in DN pathogenesis underlying DN. Investigations into this association are necessary, and novel biomarkers for the development of targeted preventive strategies against DN are needed.
AbstractList Abstract Background Earlier studies have implicated a crucial link between diabetic nephropathy (DN) and the gut microbiota (GM) by considering the gut-kidney axis; however, the specific cause-and-effect connections between these processes remain unclear. Methods To compare changes in the GM between DN patients and control subjects, a review of observational studies was performed. The examination focused on the phylum, family, genus, and species/genus categories. To delve deeper into the cause–effect relationship, instrumental variables for 211 GM taxa (9 phyla, 16 classes, 20 orders, 35 families, and 131 genera), which were eligible for the mbQTL (microbial quantitative trait locus) mapping analysis, were collected from the Genome Wide Association Study (GWAS). A Mendelian randomization investigation was then conducted to gauge their impact on DN susceptibility using data from the European Bioinformatics Institute (EBI) and the FinnGen consortium. The European Bioinformatics Institute data included 1032 DN patients and 451,248 controls, while the FinnGen consortium data consisted of 3283 DN patients and 210,463 controls. Two-sample Mendelian randomization (TSMR) was utilized to determine the link between the GM and DN. The primary method for analysis was the inverse variance weighted (IVW) approach. Moreover, a reverse Mendelian randomization analysis was carried out, and the findings were validated through sensitivity assessments. Results This review examined 11 observational studies that satisfied the inclusion and exclusion criteria. There was a significant difference in the abundance of 144 GM taxa between DN patients and controls. By employing the MR technique, 13 bacteria were pinpointed as having a causal link to DN (including 3 unknown GM taxa). Even after Bonferroni correction, the protective impact of the phylum Proteobacteria and genus Dialister (Sequeira et al. Nat Microbiol. 5:304-313, 2020; Liu et al. EBioMedicine. 90:104527, 2023) and the harmful impact of the genus Akkermansia, family Verrucomicrobiaceae, order Verrucomicrobia and class Verrucomicrobiae on DN remained significant. No noticeable heterogeneity or horizontal pleiotropy was detected in the instrumental variables (IVs). However, reverse MR investigations have failed to reveal any substantial causal relationship between DN and the GM. Conclusion Differences in the GM among DN patients and healthy controls are explored in observational studies. We verified the possible connection between certain genetically modified genera and DN, thereby emphasizing the connection between the “gut-kidney” axis and new insights into the GM’s role in DN pathogenesis underlying DN. Investigations into this association are necessary, and novel biomarkers for the development of targeted preventive strategies against DN are needed.
Earlier studies have implicated a crucial link between diabetic nephropathy (DN) and the gut microbiota (GM) by considering the gut-kidney axis; however, the specific cause-and-effect connections between these processes remain unclear. To compare changes in the GM between DN patients and control subjects, a review of observational studies was performed. The examination focused on the phylum, family, genus, and species/genus categories. To delve deeper into the cause-effect relationship, instrumental variables for 211 GM taxa (9 phyla, 16 classes, 20 orders, 35 families, and 131 genera), which were eligible for the mbQTL (microbial quantitative trait locus) mapping analysis, were collected from the Genome Wide Association Study (GWAS). A Mendelian randomization investigation was then conducted to gauge their impact on DN susceptibility using data from the European Bioinformatics Institute (EBI) and the FinnGen consortium. The European Bioinformatics Institute data included 1032 DN patients and 451,248 controls, while the FinnGen consortium data consisted of 3283 DN patients and 210,463 controls. Two-sample Mendelian randomization (TSMR) was utilized to determine the link between the GM and DN. The primary method for analysis was the inverse variance weighted (IVW) approach. Moreover, a reverse Mendelian randomization analysis was carried out, and the findings were validated through sensitivity assessments. This review examined 11 observational studies that satisfied the inclusion and exclusion criteria. There was a significant difference in the abundance of 144 GM taxa between DN patients and controls. By employing the MR technique, 13 bacteria were pinpointed as having a causal link to DN (including 3 unknown GM taxa). Even after Bonferroni correction, the protective impact of the phylum Proteobacteria and genus Dialister (Sequeira et al. Nat Microbiol. 5:304-313, 2020; Liu et al. EBioMedicine. 90:104527, 2023) and the harmful impact of the genus Akkermansia, family Verrucomicrobiaceae, order Verrucomicrobia and class Verrucomicrobiae on DN remained significant. No noticeable heterogeneity or horizontal pleiotropy was detected in the instrumental variables (IVs). However, reverse MR investigations have failed to reveal any substantial causal relationship between DN and the GM. Differences in the GM among DN patients and healthy controls are explored in observational studies. We verified the possible connection between certain genetically modified genera and DN, thereby emphasizing the connection between the "gut-kidney" axis and new insights into the GM's role in DN pathogenesis underlying DN. Investigations into this association are necessary, and novel biomarkers for the development of targeted preventive strategies against DN are needed.
Earlier studies have implicated a crucial link between diabetic nephropathy (DN) and the gut microbiota (GM) by considering the gut-kidney axis; however, the specific cause-and-effect connections between these processes remain unclear.BACKGROUNDEarlier studies have implicated a crucial link between diabetic nephropathy (DN) and the gut microbiota (GM) by considering the gut-kidney axis; however, the specific cause-and-effect connections between these processes remain unclear.To compare changes in the GM between DN patients and control subjects, a review of observational studies was performed. The examination focused on the phylum, family, genus, and species/genus categories. To delve deeper into the cause-effect relationship, instrumental variables for 211 GM taxa (9 phyla, 16 classes, 20 orders, 35 families, and 131 genera), which were eligible for the mbQTL (microbial quantitative trait locus) mapping analysis, were collected from the Genome Wide Association Study (GWAS). A Mendelian randomization investigation was then conducted to gauge their impact on DN susceptibility using data from the European Bioinformatics Institute (EBI) and the FinnGen consortium. The European Bioinformatics Institute data included 1032 DN patients and 451,248 controls, while the FinnGen consortium data consisted of 3283 DN patients and 210,463 controls. Two-sample Mendelian randomization (TSMR) was utilized to determine the link between the GM and DN. The primary method for analysis was the inverse variance weighted (IVW) approach. Moreover, a reverse Mendelian randomization analysis was carried out, and the findings were validated through sensitivity assessments.METHODSTo compare changes in the GM between DN patients and control subjects, a review of observational studies was performed. The examination focused on the phylum, family, genus, and species/genus categories. To delve deeper into the cause-effect relationship, instrumental variables for 211 GM taxa (9 phyla, 16 classes, 20 orders, 35 families, and 131 genera), which were eligible for the mbQTL (microbial quantitative trait locus) mapping analysis, were collected from the Genome Wide Association Study (GWAS). A Mendelian randomization investigation was then conducted to gauge their impact on DN susceptibility using data from the European Bioinformatics Institute (EBI) and the FinnGen consortium. The European Bioinformatics Institute data included 1032 DN patients and 451,248 controls, while the FinnGen consortium data consisted of 3283 DN patients and 210,463 controls. Two-sample Mendelian randomization (TSMR) was utilized to determine the link between the GM and DN. The primary method for analysis was the inverse variance weighted (IVW) approach. Moreover, a reverse Mendelian randomization analysis was carried out, and the findings were validated through sensitivity assessments.This review examined 11 observational studies that satisfied the inclusion and exclusion criteria. There was a significant difference in the abundance of 144 GM taxa between DN patients and controls. By employing the MR technique, 13 bacteria were pinpointed as having a causal link to DN (including 3 unknown GM taxa). Even after Bonferroni correction, the protective impact of the phylum Proteobacteria and genus Dialister (Sequeira et al. Nat Microbiol. 5:304-313, 2020; Liu et al. EBioMedicine. 90:104527, 2023) and the harmful impact of the genus Akkermansia, family Verrucomicrobiaceae, order Verrucomicrobia and class Verrucomicrobiae on DN remained significant. No noticeable heterogeneity or horizontal pleiotropy was detected in the instrumental variables (IVs). However, reverse MR investigations have failed to reveal any substantial causal relationship between DN and the GM.RESULTSThis review examined 11 observational studies that satisfied the inclusion and exclusion criteria. There was a significant difference in the abundance of 144 GM taxa between DN patients and controls. By employing the MR technique, 13 bacteria were pinpointed as having a causal link to DN (including 3 unknown GM taxa). Even after Bonferroni correction, the protective impact of the phylum Proteobacteria and genus Dialister (Sequeira et al. Nat Microbiol. 5:304-313, 2020; Liu et al. EBioMedicine. 90:104527, 2023) and the harmful impact of the genus Akkermansia, family Verrucomicrobiaceae, order Verrucomicrobia and class Verrucomicrobiae on DN remained significant. No noticeable heterogeneity or horizontal pleiotropy was detected in the instrumental variables (IVs). However, reverse MR investigations have failed to reveal any substantial causal relationship between DN and the GM.Differences in the GM among DN patients and healthy controls are explored in observational studies. We verified the possible connection between certain genetically modified genera and DN, thereby emphasizing the connection between the "gut-kidney" axis and new insights into the GM's role in DN pathogenesis underlying DN. Investigations into this association are necessary, and novel biomarkers for the development of targeted preventive strategies against DN are needed.CONCLUSIONDifferences in the GM among DN patients and healthy controls are explored in observational studies. We verified the possible connection between certain genetically modified genera and DN, thereby emphasizing the connection between the "gut-kidney" axis and new insights into the GM's role in DN pathogenesis underlying DN. Investigations into this association are necessary, and novel biomarkers for the development of targeted preventive strategies against DN are needed.
Background Earlier studies have implicated a crucial link between diabetic nephropathy (DN) and the gut microbiota (GM) by considering the gut-kidney axis; however, the specific cause-and-effect connections between these processes remain unclear. Methods To compare changes in the GM between DN patients and control subjects, a review of observational studies was performed. The examination focused on the phylum, family, genus, and species/genus categories. To delve deeper into the cause-effect relationship, instrumental variables for 211 GM taxa (9 phyla, 16 classes, 20 orders, 35 families, and 131 genera), which were eligible for the mbQTL (microbial quantitative trait locus) mapping analysis, were collected from the Genome Wide Association Study (GWAS). A Mendelian randomization investigation was then conducted to gauge their impact on DN susceptibility using data from the European Bioinformatics Institute (EBI) and the FinnGen consortium. The European Bioinformatics Institute data included 1032 DN patients and 451,248 controls, while the FinnGen consortium data consisted of 3283 DN patients and 210,463 controls. Two-sample Mendelian randomization (TSMR) was utilized to determine the link between the GM and DN. The primary method for analysis was the inverse variance weighted (IVW) approach. Moreover, a reverse Mendelian randomization analysis was carried out, and the findings were validated through sensitivity assessments. Results This review examined 11 observational studies that satisfied the inclusion and exclusion criteria. There was a significant difference in the abundance of 144 GM taxa between DN patients and controls. By employing the MR technique, 13 bacteria were pinpointed as having a causal link to DN (including 3 unknown GM taxa). Even after Bonferroni correction, the protective impact of the phylum Proteobacteria and genus Dialister (Sequeira et al. Nat Microbiol. 5:304-313, 2020; Liu et al. EBioMedicine. 90:104527, 2023) and the harmful impact of the genus Akkermansia, family Verrucomicrobiaceae, order Verrucomicrobia and class Verrucomicrobiae on DN remained significant. No noticeable heterogeneity or horizontal pleiotropy was detected in the instrumental variables (IVs). However, reverse MR investigations have failed to reveal any substantial causal relationship between DN and the GM. Conclusion Differences in the GM among DN patients and healthy controls are explored in observational studies. We verified the possible connection between certain genetically modified genera and DN, thereby emphasizing the connection between the "gut-kidney" axis and new insights into the GM's role in DN pathogenesis underlying DN. Investigations into this association are necessary, and novel biomarkers for the development of targeted preventive strategies against DN are needed. Keywords: Diabetic nephropathy, Gut-kidney axis, Gut microbiota, Mendelian randomization, Observational studies
BackgroundEarlier studies have implicated a crucial link between diabetic nephropathy (DN) and the gut microbiota (GM) by considering the gut-kidney axis; however, the specific cause-and-effect connections between these processes remain unclear.MethodsTo compare changes in the GM between DN patients and control subjects, a review of observational studies was performed. The examination focused on the phylum, family, genus, and species/genus categories. To delve deeper into the cause–effect relationship, instrumental variables for 211 GM taxa (9 phyla, 16 classes, 20 orders, 35 families, and 131 genera), which were eligible for the mbQTL (microbial quantitative trait locus) mapping analysis, were collected from the Genome Wide Association Study (GWAS). A Mendelian randomization investigation was then conducted to gauge their impact on DN susceptibility using data from the European Bioinformatics Institute (EBI) and the FinnGen consortium. The European Bioinformatics Institute data included 1032 DN patients and 451,248 controls, while the FinnGen consortium data consisted of 3283 DN patients and 210,463 controls. Two-sample Mendelian randomization (TSMR) was utilized to determine the link between the GM and DN. The primary method for analysis was the inverse variance weighted (IVW) approach. Moreover, a reverse Mendelian randomization analysis was carried out, and the findings were validated through sensitivity assessments.ResultsThis review examined 11 observational studies that satisfied the inclusion and exclusion criteria. There was a significant difference in the abundance of 144 GM taxa between DN patients and controls. By employing the MR technique, 13 bacteria were pinpointed as having a causal link to DN (including 3 unknown GM taxa). Even after Bonferroni correction, the protective impact of the phylum Proteobacteria and genus Dialister (Sequeira et al. Nat Microbiol. 5:304-313, 2020; Liu et al. EBioMedicine. 90:104527, 2023) and the harmful impact of the genus Akkermansia, family Verrucomicrobiaceae, order Verrucomicrobia and class Verrucomicrobiae on DN remained significant. No noticeable heterogeneity or horizontal pleiotropy was detected in the instrumental variables (IVs). However, reverse MR investigations have failed to reveal any substantial causal relationship between DN and the GM.ConclusionDifferences in the GM among DN patients and healthy controls are explored in observational studies. We verified the possible connection between certain genetically modified genera and DN, thereby emphasizing the connection between the “gut-kidney” axis and new insights into the GM’s role in DN pathogenesis underlying DN. Investigations into this association are necessary, and novel biomarkers for the development of targeted preventive strategies against DN are needed.
Earlier studies have implicated a crucial link between diabetic nephropathy (DN) and the gut microbiota (GM) by considering the gut-kidney axis; however, the specific cause-and-effect connections between these processes remain unclear. To compare changes in the GM between DN patients and control subjects, a review of observational studies was performed. The examination focused on the phylum, family, genus, and species/genus categories. To delve deeper into the cause-effect relationship, instrumental variables for 211 GM taxa (9 phyla, 16 classes, 20 orders, 35 families, and 131 genera), which were eligible for the mbQTL (microbial quantitative trait locus) mapping analysis, were collected from the Genome Wide Association Study (GWAS). A Mendelian randomization investigation was then conducted to gauge their impact on DN susceptibility using data from the European Bioinformatics Institute (EBI) and the FinnGen consortium. The European Bioinformatics Institute data included 1032 DN patients and 451,248 controls, while the FinnGen consortium data consisted of 3283 DN patients and 210,463 controls. Two-sample Mendelian randomization (TSMR) was utilized to determine the link between the GM and DN. The primary method for analysis was the inverse variance weighted (IVW) approach. Moreover, a reverse Mendelian randomization analysis was carried out, and the findings were validated through sensitivity assessments. This review examined 11 observational studies that satisfied the inclusion and exclusion criteria. There was a significant difference in the abundance of 144 GM taxa between DN patients and controls. By employing the MR technique, 13 bacteria were pinpointed as having a causal link to DN (including 3 unknown GM taxa). Even after Bonferroni correction, the protective impact of the phylum Proteobacteria and genus Dialister (Sequeira et al. Nat Microbiol. 5:304-313, 2020; Liu et al. EBioMedicine. 90:104527, 2023) and the harmful impact of the genus Akkermansia, family Verrucomicrobiaceae, order Verrucomicrobia and class Verrucomicrobiae on DN remained significant. No noticeable heterogeneity or horizontal pleiotropy was detected in the instrumental variables (IVs). However, reverse MR investigations have failed to reveal any substantial causal relationship between DN and the GM. Differences in the GM among DN patients and healthy controls are explored in observational studies. We verified the possible connection between certain genetically modified genera and DN, thereby emphasizing the connection between the "gut-kidney" axis and new insights into the GM's role in DN pathogenesis underlying DN. Investigations into this association are necessary, and novel biomarkers for the development of targeted preventive strategies against DN are needed.
ArticleNumber 101
Audience Academic
Author Jia, Jia Meng
Du, Bo Xuan
Zhu, Xing Yu
Han, Yi Zhen
Wang, Yang Zhi Yuan
Zheng, Hui Juan
Wang, Yao Xian
Zhang, Xue Qin
Liu, Wei Jing
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/40122887$$D View this record in MEDLINE/PubMed
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Issue 1
Keywords Gut microbiota
Diabetic nephropathy
Mendelian randomization
Gut–kidney axis
Observational studies
Language English
License 2025. The Author(s).
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Snippet Earlier studies have implicated a crucial link between diabetic nephropathy (DN) and the gut microbiota (GM) by considering the gut-kidney axis; however, the...
Background Earlier studies have implicated a crucial link between diabetic nephropathy (DN) and the gut microbiota (GM) by considering the gut-kidney axis;...
BackgroundEarlier studies have implicated a crucial link between diabetic nephropathy (DN) and the gut microbiota (GM) by considering the gut-kidney axis;...
Abstract Background Earlier studies have implicated a crucial link between diabetic nephropathy (DN) and the gut microbiota (GM) by considering the gut-kidney...
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SubjectTerms Analysis
Confounding (Statistics)
Diabetes
Diabetic nephropathies
Diabetic Nephropathies - genetics
Diabetic Nephropathies - microbiology
Diabetic nephropathy
Ethics
Gastrointestinal Microbiome - genetics
Genetically modified organisms
Genome-Wide Association Study
Genomes
Genomics
Gut microbiota
Gut–kidney axis
Humans
Kidney diseases
Mapping
Mendelian randomization
Mendelian Randomization Analysis
Metabolism
Microbiota
Microbiota (Symbiotic organisms)
Observational studies
Observational Studies as Topic
Review
Sample size
Variables
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Title The gut microbiota and diabetic nephropathy: an observational study review and bidirectional Mendelian randomization study
URI https://www.ncbi.nlm.nih.gov/pubmed/40122887
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Volume 26
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