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

MACARENA OREJUDO DEL RÍO^1*Manuel J Gómez²Sabino Riestra Menendez³Montserrat Rivero⁴Ana Gutiérrez⁵Iago Rodríguez-Lago⁶Luis Fernández⁷Daniel Ceballos⁸José Manuel Benítez⁹Mariam Aguas¹⁰Iria Baston Rey¹¹Fernando Bermejo¹²María José Casanova¹Rufo H Lorente-Poyatos¹³Yolanda Ber¹⁴Daniel Ginard¹⁵María Esteve¹⁶Ruth de Francisco³María José García⁴Rubén Francés¹⁷Ainhoa Rodríguez⁶Noelia Alcaide Suárez⁷Elena Guerra del Río⁸Pilar Soto⁹Pilar Nos¹⁰Manuel Barreiro-de Acosta¹¹Ivan Guerra¹²Daniel Hervías Cruz¹³Manuel Domínguez Cajal¹⁴Vanesa Royo¹⁵Montserrat Aceituno¹⁶Laila Aldars-García¹Ana Garre¹Cristina Ramírez¹Irene Soleto¹Ina Schuppe Koistinen¹⁸Lars Engstrand¹⁸Montse Baldán-Martín¹Fatima Sanchez-cabo²Javier P Gisbert¹María Chaparro^1*

• ¹Fundación Biomédica, Hospital de La Princesa, Madrid, Spain
• ²Spanish National Centre for Cardiovascular Research, Madrid, Catalonia, Spain
• ³Digestive Service, Central University Hospital of Asturias (HUCA), Oviedo, Spain
• ⁴Marqués de Valdecilla Health Research Institute (IDIVAL), Santander, Cantabria, Spain
• ⁵Instituto de Investigaciones Biomédicas y Sanitarias de Alicante, Hospital General Universitario de Alicante, Alicante, Spain
• ⁶Galdakao University Hospital, Galdakao, Spain
• ⁷Hospital Clínico Universitario de Valladolid, Valladolid, Spain
• ⁸University Hospital of Gran Canaria Dr. Negrin, Las Palmas de Gran Canaria, Spain
• ⁹Reina Sofia University Hospital, Cordoba, Spain
• ¹⁰La Fe Health Research Institute, Valencia, Valencia, Spain
• ¹¹Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Galicia, Spain
• ¹²Fuenlabrada University Hospital, Madrid, Madrid, Spain
• ¹³Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
• ¹⁴Hospital General San Jorge, Huesca, Spain
• ¹⁵Hospital Universitario Son Espases, Palma de Mallorca, Spain
• ¹⁶Department of Gastroenterology, Mútua Terrassa University Hospital, Barcelona, Catalonia, Spain
• ¹⁷Institute of Research, Development and Innovation in Healthcare Biotechnology of Elche (IDiBE), Elche, Spain
• ¹⁸Centre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet (KI), Stockholm, Stockholm, Sweden

Dysbiosis 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. Microbiota from stool samples were investigated using shotgun metagenomics sequencing and subsequent bioinformatics analysis. A 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. Our 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.