Reduced butyrate-producing bacteria and altered metabolic pathways in the gut microbiome of immunoglobulin A nephropathy patients

Abstract Gut-associated lymphoid tissue is central to the production of galactose-deficient IgA1 (Gd-IgA1), a key factor in immunoglobulin A nephropathy (IgAN). Although no major differences in gut microbiome diversity have been reported across IgAN cohorts, functional alterations in microbial compo...

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Main Authors: Anna Popova, Kārlis Rācenis, Monta Brīvība, Rihards Saksis, Mikus Saulīte, Baiba Šlisere, Egija Berga-Švītiņa, Kristīne Oļeiņika, Anna Jana Saulīte, Jānis Seilis, Juta Kroiča, Harijs Čerņevskis, Aivars Pētersons, Jānis Kloviņš, Aivars Lejnieks, Viktorija Kuzema
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-13629-5
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author Anna Popova
Kārlis Rācenis
Monta Brīvība
Rihards Saksis
Mikus Saulīte
Baiba Šlisere
Egija Berga-Švītiņa
Kristīne Oļeiņika
Anna Jana Saulīte
Jānis Seilis
Juta Kroiča
Harijs Čerņevskis
Aivars Pētersons
Jānis Kloviņš
Aivars Lejnieks
Viktorija Kuzema
author_facet Anna Popova
Kārlis Rācenis
Monta Brīvība
Rihards Saksis
Mikus Saulīte
Baiba Šlisere
Egija Berga-Švītiņa
Kristīne Oļeiņika
Anna Jana Saulīte
Jānis Seilis
Juta Kroiča
Harijs Čerņevskis
Aivars Pētersons
Jānis Kloviņš
Aivars Lejnieks
Viktorija Kuzema
author_sort Anna Popova
collection DOAJ
description Abstract Gut-associated lymphoid tissue is central to the production of galactose-deficient IgA1 (Gd-IgA1), a key factor in immunoglobulin A nephropathy (IgAN). Although no major differences in gut microbiome diversity have been reported across IgAN cohorts, functional alterations in microbial composition may contribute to disease pathogenesis. The study was designed as a cross-sectional study with an embedded prospective cohort component. Forty-eight adults with biopsy-confirmed IgAN—categorized as progressors (eGFR decline > 5 ml/min/1.73 m²/year, n = 23) or nonprogressors (n = 23)—and 23 healthy controls (HC) were recruited. Stool samples underwent metagenomic and functional profiling. Alpha diversity did not differ significantly between IgAN patients and HC. However, butyrate-producing bacteria (Butyrococcus, Agathobacter rectalis) were less abundant in IgAN patients. The sulfoquinovose degradation I pathway, associated with these bacteria, was also reduced. Nucleotide- and nucleoside-biosynthesis pathways were elevated in IgAN. Gd-IgA1 levels correlated with variations in metabolic pathways. Progressors demonstrated enhanced activity in isopropanol biosynthesis, biotin biosynthesis II, and phospholipid biosynthesis pathways. IgAN patients show reduced butyrate-producing bacteria and distinct functional changes in the gut microbiome suggestive of immune activation and inflammation. Progressors exhibit additional metabolic shifts linked to bacterial membrane stabilization.
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spelling doaj-art-ed3f87ec7a0f4ae78d202945773c251e2025-08-20T03:46:01ZengNature PortfolioScientific Reports2045-23222025-07-0115111010.1038/s41598-025-13629-5Reduced butyrate-producing bacteria and altered metabolic pathways in the gut microbiome of immunoglobulin A nephropathy patientsAnna Popova0Kārlis Rācenis1Monta Brīvība2Rihards Saksis3Mikus Saulīte4Baiba Šlisere5Egija Berga-Švītiņa6Kristīne Oļeiņika7Anna Jana Saulīte8Jānis Seilis9Juta Kroiča10Harijs Čerņevskis11Aivars Pētersons12Jānis Kloviņš13Aivars Lejnieks14Viktorija Kuzema15Department of Internal Diseases, Riga Stradins UniversityDepartment of Internal Diseases, Riga Stradins UniversityLatvian Biomedical Research and Study CentreLatvian Biomedical Research and Study CentreDepartment of Internal Diseases, Riga Stradins UniversityJoint Laboratory, Pauls Stradins Clinical University HospitalInstitute of Oncology, Riga Stradins UniversityDepartment of Internal Diseases, Riga Stradins UniversityCenter of Nephrology, Pauls Stradins Clinical University HospitalDepartment of Internal Diseases, Riga Stradins UniversityDepartment of Biology and Microbiology, Riga Stradins UniversityDepartment of Internal Diseases, Riga Stradins UniversityDepartment of Internal Diseases, Riga Stradins UniversityLatvian Biomedical Research and Study CentreDepartment of Internal Diseases, Riga Stradins UniversityDepartment of Internal Diseases, Riga Stradins UniversityAbstract Gut-associated lymphoid tissue is central to the production of galactose-deficient IgA1 (Gd-IgA1), a key factor in immunoglobulin A nephropathy (IgAN). Although no major differences in gut microbiome diversity have been reported across IgAN cohorts, functional alterations in microbial composition may contribute to disease pathogenesis. The study was designed as a cross-sectional study with an embedded prospective cohort component. Forty-eight adults with biopsy-confirmed IgAN—categorized as progressors (eGFR decline > 5 ml/min/1.73 m²/year, n = 23) or nonprogressors (n = 23)—and 23 healthy controls (HC) were recruited. Stool samples underwent metagenomic and functional profiling. Alpha diversity did not differ significantly between IgAN patients and HC. However, butyrate-producing bacteria (Butyrococcus, Agathobacter rectalis) were less abundant in IgAN patients. The sulfoquinovose degradation I pathway, associated with these bacteria, was also reduced. Nucleotide- and nucleoside-biosynthesis pathways were elevated in IgAN. Gd-IgA1 levels correlated with variations in metabolic pathways. Progressors demonstrated enhanced activity in isopropanol biosynthesis, biotin biosynthesis II, and phospholipid biosynthesis pathways. IgAN patients show reduced butyrate-producing bacteria and distinct functional changes in the gut microbiome suggestive of immune activation and inflammation. Progressors exhibit additional metabolic shifts linked to bacterial membrane stabilization.https://doi.org/10.1038/s41598-025-13629-5Gut microbiomeImmunoglobulin a nephropathyProgressorsButyrate-producing bacteria
spellingShingle Anna Popova
Kārlis Rācenis
Monta Brīvība
Rihards Saksis
Mikus Saulīte
Baiba Šlisere
Egija Berga-Švītiņa
Kristīne Oļeiņika
Anna Jana Saulīte
Jānis Seilis
Juta Kroiča
Harijs Čerņevskis
Aivars Pētersons
Jānis Kloviņš
Aivars Lejnieks
Viktorija Kuzema
Reduced butyrate-producing bacteria and altered metabolic pathways in the gut microbiome of immunoglobulin A nephropathy patients
Scientific Reports
Gut microbiome
Immunoglobulin a nephropathy
Progressors
Butyrate-producing bacteria
title Reduced butyrate-producing bacteria and altered metabolic pathways in the gut microbiome of immunoglobulin A nephropathy patients
title_full Reduced butyrate-producing bacteria and altered metabolic pathways in the gut microbiome of immunoglobulin A nephropathy patients
title_fullStr Reduced butyrate-producing bacteria and altered metabolic pathways in the gut microbiome of immunoglobulin A nephropathy patients
title_full_unstemmed Reduced butyrate-producing bacteria and altered metabolic pathways in the gut microbiome of immunoglobulin A nephropathy patients
title_short Reduced butyrate-producing bacteria and altered metabolic pathways in the gut microbiome of immunoglobulin A nephropathy patients
title_sort reduced butyrate producing bacteria and altered metabolic pathways in the gut microbiome of immunoglobulin a nephropathy patients
topic Gut microbiome
Immunoglobulin a nephropathy
Progressors
Butyrate-producing bacteria
url https://doi.org/10.1038/s41598-025-13629-5
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