Exploration of fecal microbiota in newly diagnosed patients with inflammatory bowel disease using shotgun metagenomics

IntroductionDysbiosis is a key mechanism in inflammatory bowel disease (IBD) pathophysiology. Previous microbiota studies in IBD generally have involved patients treated with immunosuppressive agents, which can affect the results. We aimed to elucidate the fecal microbiota composition in newly diagn...

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Main Authors: Macarena Orejudo, Manuel J. Gómez, Sabino Riestra, Montserrat Rivero, Ana Gutiérrez, Iago Rodríguez-Lago, Luis Fernández-Salazar, Daniel Ceballos, José Manuel Benítez, Mariam Aguas, Iria Bastón-Rey, Fernando Bermejo, María José Casanova, Rufo H. Lorente-Poyatos, Yolanda Ber, Daniel Ginard, María Esteve, Ruth de Francisco, María José García, Rubén Francés, Ainhoa Rodríguez, Noelia Alcaide Suárez, Elena Guerra del Río, Pilar Soto, Pilar Nos, Manuel Barreiro-de Acosta, Iván Guerra, Daniel Hervías Cruz, Manuel Domínguez Cajal, Vanesa Royo, Montserrat Aceituno, Laila Aldars-García, Ana Garre, Cristina Ramírez, Irene Soleto, Ina Schuppe-Koistinen, Lars Engstrand, Montse Baldán-Martín, Fátima Sánchez-Cabo, Javier P. Gisbert, María Chaparro
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Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2025.1595884/full
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author Macarena Orejudo
Manuel J. Gómez
Sabino Riestra
Montserrat Rivero
Ana Gutiérrez
Iago Rodríguez-Lago
Luis Fernández-Salazar
Daniel Ceballos
José Manuel Benítez
Mariam Aguas
Iria Bastón-Rey
Fernando Bermejo
María José Casanova
Rufo H. Lorente-Poyatos
Yolanda Ber
Daniel Ginard
María Esteve
Ruth de Francisco
María José García
Rubén Francés
Rubén Francés
Ainhoa Rodríguez
Noelia Alcaide Suárez
Elena Guerra del Río
Pilar Soto
Pilar Nos
Manuel Barreiro-de Acosta
Iván Guerra
Daniel Hervías Cruz
Manuel Domínguez Cajal
Vanesa Royo
Montserrat Aceituno
Laila Aldars-García
Ana Garre
Cristina Ramírez
Irene Soleto
Ina Schuppe-Koistinen
Lars Engstrand
Montse Baldán-Martín
Fátima Sánchez-Cabo
Javier P. Gisbert
María Chaparro
author_facet Macarena Orejudo
Manuel J. Gómez
Sabino Riestra
Montserrat Rivero
Ana Gutiérrez
Iago Rodríguez-Lago
Luis Fernández-Salazar
Daniel Ceballos
José Manuel Benítez
Mariam Aguas
Iria Bastón-Rey
Fernando Bermejo
María José Casanova
Rufo H. Lorente-Poyatos
Yolanda Ber
Daniel Ginard
María Esteve
Ruth de Francisco
María José García
Rubén Francés
Rubén Francés
Ainhoa Rodríguez
Noelia Alcaide Suárez
Elena Guerra del Río
Pilar Soto
Pilar Nos
Manuel Barreiro-de Acosta
Iván Guerra
Daniel Hervías Cruz
Manuel Domínguez Cajal
Vanesa Royo
Montserrat Aceituno
Laila Aldars-García
Ana Garre
Cristina Ramírez
Irene Soleto
Ina Schuppe-Koistinen
Lars Engstrand
Montse Baldán-Martín
Fátima Sánchez-Cabo
Javier P. Gisbert
María Chaparro
author_sort Macarena Orejudo
collection DOAJ
description IntroductionDysbiosis is a key mechanism in inflammatory bowel disease (IBD) pathophysiology. Previous microbiota studies in IBD generally have involved patients treated with immunosuppressive agents, which can affect the results. We aimed to elucidate the fecal microbiota composition in newly diagnosed treatment-naïve IBD patients.MethodsMicrobiota from stool samples were investigated using shotgun metagenomics sequencing and subsequent bioinformatics analysis.ResultsA total of 103 patients with Crohn's disease (CD), 144 with ulcerative colitis (UC), and 49 healthy controls (HC) were included. CD patients had significantly lower species-level diversity than those with UC and HC. CD subgroups with Ileocolonic location and stricturing behavior showed reduced diversity compared to HC. A negative correlation was observed between endoscopic severity and microbial diversity in CD patients. UC patients had similar microbial diversity to HC, which was unaffected by disease activity. Taxonomic abundance analysis revealed a tendency towards a higher relative abundance of Escherichia coli and a lower relative abundance of Faecalibacterium prausnitzii in IBD patients compared to HC. However, the most significant differences in these patients compared to HC were observed in less abundant species, such as Toxoplasma gondii, Gemella morbillorum, and several species of the Adlercreutzia genera. Functional analysis in these patients highlighted changes in carbohydrate and nucleotide pathways.DiscussionOur data suggest that newly diagnosed CD patients show significant microbiota composition disparities compared to UC patients and HC. Microbiota differences in these patients are linked to dysbiosis, characterized by a reduction in beneficial genera such as Gemella and Adlercreutzia, and a rise in pathogenic species.
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spelling doaj-art-8e48bb9c4f0949e19d96c8ebea63859e2025-08-20T03:28:21ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-07-011510.3389/fcimb.2025.15958841595884Exploration of fecal microbiota in newly diagnosed patients with inflammatory bowel disease using shotgun metagenomicsMacarena Orejudo0Manuel J. Gómez1Sabino Riestra2Montserrat Rivero3Ana Gutiérrez4Iago Rodríguez-Lago5Luis Fernández-Salazar6Daniel Ceballos7José Manuel Benítez8Mariam Aguas9Iria Bastón-Rey10Fernando Bermejo11María José Casanova12Rufo H. Lorente-Poyatos13Yolanda Ber14Daniel Ginard15María Esteve16Ruth de Francisco17María José García18Rubén Francés19Rubén Francés20Ainhoa Rodríguez21Noelia Alcaide Suárez22Elena Guerra del Río23Pilar Soto24Pilar Nos25Manuel Barreiro-de Acosta26Iván Guerra27Daniel Hervías Cruz28Manuel Domínguez Cajal29Vanesa Royo30Montserrat Aceituno31Laila Aldars-García32Ana Garre33Cristina Ramírez34Irene Soleto35Ina Schuppe-Koistinen36Lars Engstrand37Montse Baldán-Martín38Fátima Sánchez-Cabo39Javier P. Gisbert40María Chaparro41Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, SpainCentro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, SpainGastroenterology Department, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Asturias, SpainGastroenterology Department, Hospital Universitario Marqués de Valdecilla, Grupo de Investigación Clínica y Traslacional en Enfermedades Digestivas, Instituto de Investigación Valdecilla (IDIVAL), Santander, SpainHospital General Universitario Dr Balmis de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL) y Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Alicante, SpainGastroenterology Department, Hospital Universitario de Galdakao, Galdakao, Vizcaya, SpainBiobizkaia Health Research Institute, Galdakao, Vizcaya, SpainGastroenterology Department, Hospital Clínico Universitario de Valladolid, Universidad de Valladolid, Valladolid, SpainGastroenterology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain0Gastroenterology Department, Hospital Universitario Reina Sofía and Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain1Hospital Universitario La Fe, Health Research Institute La Fe, Valencia, Spain2Complexo Hospitalario Universitario de Santiago, Santiago de Compostela, SpainHospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain3Hospital Universitario de Fuenlabrada, Madrid, Spain4Hospital General Universitario de Ciudad Real, Ciudad Real, Spain5Hospital San Jorge, Huesca, Spain6Hospital Universitari Son Espases, Palma de Mallorca, SpainGastroenterology Department, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Asturias, SpainGastroenterology Department, Hospital Universitario Marqués de Valdecilla, Grupo de Investigación Clínica y Traslacional en Enfermedades Digestivas, Instituto de Investigación Valdecilla (IDIVAL), Santander, Spain7Hospital Universitari Mutua Terrassa, Terrassa, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain8Grupo de Inmunobiología Hepática e Intestinal, Dpto. Medicina Clínica e Instituto Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDIBE), Universidad Miguel Hernández, San Juan, Alicante, SpainGastroenterology Department, Hospital Universitario de Galdakao, Galdakao, Vizcaya, SpainBiobizkaia Health Research Institute, Galdakao, Vizcaya, SpainGastroenterology Department, Hospital Clínico Universitario de Valladolid, Universidad de Valladolid, Valladolid, SpainGastroenterology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain0Gastroenterology Department, Hospital Universitario Reina Sofía and Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain1Hospital Universitario La Fe, Health Research Institute La Fe, Valencia, Spain2Complexo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain3Hospital Universitario de Fuenlabrada, Madrid, Spain4Hospital General Universitario de Ciudad Real, Ciudad Real, Spain5Hospital San Jorge, Huesca, Spain6Hospital Universitari Son Espases, Palma de Mallorca, SpainHospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, SpainHospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, SpainHospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, SpainHospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain9Centre for Translational Microbiome Research, Department Microbiology, Tumor and Cell Biology, Karolinska Institute, Solna, Sweden9Centre for Translational Microbiome Research, Department Microbiology, Tumor and Cell Biology, Karolinska Institute, Solna, SwedenHospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, SpainCentro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, SpainHospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, SpainHospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, SpainIntroductionDysbiosis is a key mechanism in inflammatory bowel disease (IBD) pathophysiology. Previous microbiota studies in IBD generally have involved patients treated with immunosuppressive agents, which can affect the results. We aimed to elucidate the fecal microbiota composition in newly diagnosed treatment-naïve IBD patients.MethodsMicrobiota from stool samples were investigated using shotgun metagenomics sequencing and subsequent bioinformatics analysis.ResultsA total of 103 patients with Crohn's disease (CD), 144 with ulcerative colitis (UC), and 49 healthy controls (HC) were included. CD patients had significantly lower species-level diversity than those with UC and HC. CD subgroups with Ileocolonic location and stricturing behavior showed reduced diversity compared to HC. A negative correlation was observed between endoscopic severity and microbial diversity in CD patients. UC patients had similar microbial diversity to HC, which was unaffected by disease activity. Taxonomic abundance analysis revealed a tendency towards a higher relative abundance of Escherichia coli and a lower relative abundance of Faecalibacterium prausnitzii in IBD patients compared to HC. However, the most significant differences in these patients compared to HC were observed in less abundant species, such as Toxoplasma gondii, Gemella morbillorum, and several species of the Adlercreutzia genera. Functional analysis in these patients highlighted changes in carbohydrate and nucleotide pathways.DiscussionOur data suggest that newly diagnosed CD patients show significant microbiota composition disparities compared to UC patients and HC. Microbiota differences in these patients are linked to dysbiosis, characterized by a reduction in beneficial genera such as Gemella and Adlercreutzia, and a rise in pathogenic species.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1595884/fullinflammatory bowel diseaseCrohn’s diseaseulcerative colitismicrobiotametagenomicsshotgun
spellingShingle Macarena Orejudo
Manuel J. Gómez
Sabino Riestra
Montserrat Rivero
Ana Gutiérrez
Iago Rodríguez-Lago
Luis Fernández-Salazar
Daniel Ceballos
José Manuel Benítez
Mariam Aguas
Iria Bastón-Rey
Fernando Bermejo
María José Casanova
Rufo H. Lorente-Poyatos
Yolanda Ber
Daniel Ginard
María Esteve
Ruth de Francisco
María José García
Rubén Francés
Rubén Francés
Ainhoa Rodríguez
Noelia Alcaide Suárez
Elena Guerra del Río
Pilar Soto
Pilar Nos
Manuel Barreiro-de Acosta
Iván Guerra
Daniel Hervías Cruz
Manuel Domínguez Cajal
Vanesa Royo
Montserrat Aceituno
Laila Aldars-García
Ana Garre
Cristina Ramírez
Irene Soleto
Ina Schuppe-Koistinen
Lars Engstrand
Montse Baldán-Martín
Fátima Sánchez-Cabo
Javier P. Gisbert
María Chaparro
Exploration of fecal microbiota in newly diagnosed patients with inflammatory bowel disease using shotgun metagenomics
Frontiers in Cellular and Infection Microbiology
inflammatory bowel disease
Crohn’s disease
ulcerative colitis
microbiota
metagenomics
shotgun
title Exploration of fecal microbiota in newly diagnosed patients with inflammatory bowel disease using shotgun metagenomics
title_full Exploration of fecal microbiota in newly diagnosed patients with inflammatory bowel disease using shotgun metagenomics
title_fullStr Exploration of fecal microbiota in newly diagnosed patients with inflammatory bowel disease using shotgun metagenomics
title_full_unstemmed Exploration of fecal microbiota in newly diagnosed patients with inflammatory bowel disease using shotgun metagenomics
title_short Exploration of fecal microbiota in newly diagnosed patients with inflammatory bowel disease using shotgun metagenomics
title_sort exploration of fecal microbiota in newly diagnosed patients with inflammatory bowel disease using shotgun metagenomics
topic inflammatory bowel disease
Crohn’s disease
ulcerative colitis
microbiota
metagenomics
shotgun
url https://www.frontiersin.org/articles/10.3389/fcimb.2025.1595884/full
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