Gut microbiota and metabolome signatures in obese and normal-weight patients with colorectal tumors

Marta La Vecchia; Michela Giulia Clavenna; Marika Sculco; Gloria Sala; Denise Marradi; Elettra Barberis; Soni Joseph; Marta Mellai; Nico Pagano; Renzo Boldorini; Barbara Azzimonti; Elisa Bona; Edoardo Pasolli; Flavia Prodam; Carlotta Sacerdote; Daniela Ferrante; Emilia Ghelardi; Marcello Manfredi; Anna Aspesi; Irma Dianzani

doi:10.1016/j.isci.2025.112221

Gut microbiota and metabolome signatures in obese and normal-weight patients with colorectal tumors

iScience. 2025 Mar 13;28(4):112221. doi: 10.1016/j.isci.2025.112221. eCollection 2025 Apr 18.

Authors

Marta La Vecchia¹, Michela Giulia Clavenna¹, Marika Sculco¹, Gloria Sala¹, Denise Marradi^{2

3}, Elettra Barberis^{3

4}, Soni Joseph¹, Marta Mellai^{1

3}, Nico Pagano⁵, Renzo Boldorini^{1

6}, Barbara Azzimonti^{1

3}, Elisa Bona^{3

7

8}, Edoardo Pasolli^{9

10}, Flavia Prodam^{1

11}, Carlotta Sacerdote¹, Daniela Ferrante², Emilia Ghelardi¹², Marcello Manfredi^{2

3}, Anna Aspesi¹, Irma Dianzani¹

Affiliations

¹ Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy.
² Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy.
³ Center for Translational Research on Autoimmune and Allergic Diseases, University of Piemonte Orientale, 28100 Novara, Italy.
⁴ Department of Sciences and Technological Innovation, Università del Piemonte Orientale, 15121 Alessandria, Italy.
⁵ Department of Gastroenterology, University Hospital "Maggiore della Carità", 28100 Novara, Italy.
⁶ Pathology Unit, University Hospital "Maggiore della Carità", 28100 Novara, Italy.
⁷ Department for Sustainable Development and Ecological Transition, Università del Piemonte Orientale, 13100 Vercelli, Italy.
⁸ Simple Departmental Structure Research Laboratories - Integrated Activities Research and Innovation Department, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy.
⁹ Department of Agricultural Sciences, Division of Microbiology, University of Naples Federico II, 80055 Portici, Italy.
¹⁰ Task Force on Microbiome Studies, University of Naples Federico II, 80055 Portici, Italy.
¹¹ SCDU Endocrinology, University Hospital "Maggiore della Carità", Department of Translational Medicine, University of Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy.
¹² Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56127 Pisa, Italy.

Abstract

Here, we aim to improve our understanding of various colorectal cancer (CRC) risk factors (obesity, unhealthy diet, and gut microbiota/metabolome alteration), analyzing 120 patients with colon polyps, divided in normal-weight (NW) or overweight/obese (OB). Dietary habits data (validated EPIC questionnaires) revealed a higher consumption of processed meat among OB vs. NW patients. Both mucosa-associated microbiota (MAM) on polyps and lumen-associated microbiota (LAM) analyses uncovered distinct bacterial signatures in the two groups. Importantly, we found an enrichment of the pathogenic species Finegoldia magna in MAM of OB patients, regardless of their polyp stage. We observed distinct mucosal-associated metabolome signatures, with OB patients showing increased pyroglutamic acid and reduced niacin levels, and performed microbiota-metabolome integrated analysis. These findings support a model where different risk factors may contribute to tumorigenesis in OB vs. NW patients, highlighting the potential impact of processed meat consumption and F. magna on CRC development among OB patients.

Keywords: Cancer systems biology; Health sciences; Metabolomics; Microbiome.