Long-lasting gut microbiome and fecal metabolome alterations after colorectal adenoma removal and their relationship to colorectal cancer

Ana Nogal; Kai Wang; Kelsey N Thompson; Hanseul Kim; Amrisha Bhosle; Gianmarco Piccinno; Sagun Maharjan; Chahat Upreti; Long H Nguyen; Nicola Segata; Eric B Rimm; Wendy S Garrett; Andrew T Chan; Curtis Huttenhower; Mingyang Song

doi:10.1016/j.chom.2026.05.001

Long-lasting gut microbiome and fecal metabolome alterations after colorectal adenoma removal and their relationship to colorectal cancer

Cell Host Microbe. 2026 Jun 10;34(6):1135-1150.e6. doi: 10.1016/j.chom.2026.05.001. Epub 2026 May 27.

Authors

Ana Nogal¹, Kai Wang², Kelsey N Thompson³, Hanseul Kim⁴, Amrisha Bhosle⁵, Gianmarco Piccinno⁶, Sagun Maharjan⁷, Chahat Upreti³, Long H Nguyen⁵, Nicola Segata⁸, Eric B Rimm⁹, Wendy S Garrett¹⁰, Andrew T Chan¹¹, Curtis Huttenhower¹², Mingyang Song¹³

Affiliations

¹ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Harvard Chan Microbiome in Public Health Center, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
² Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Harvard Chan Microbiome in Public Health Center, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
³ Harvard Chan Microbiome in Public Health Center, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
⁴ Harvard Chan Microbiome in Public Health Center, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
⁵ Harvard Chan Microbiome in Public Health Center, Boston, MA 02115, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
⁶ Department CIBIO, University of Trento, Trento 38123, Italy.
⁷ Harvard Chan Microbiome in Public Health Center, Boston, MA 02115, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
⁸ Department CIBIO, University of Trento, Trento 38123, Italy; IEO, European Institute of Oncology, IRCCS, Milan 20141, Italy.
⁹ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Harvard Chan Microbiome in Public Health Center, Boston, MA 02115, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
¹⁰ Harvard Chan Microbiome in Public Health Center, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
¹¹ Harvard Chan Microbiome in Public Health Center, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
¹² Harvard Chan Microbiome in Public Health Center, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
¹³ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Harvard Chan Microbiome in Public Health Center, Boston, MA 02115, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: msong@hsph.harvard.edu.

PMID: 42202778
DOI: 10.1016/j.chom.2026.05.001

Abstract

Although the gut microbiome is implicated in colorectal cancer (CRC), microbiome and metabolome alterations along the adenoma-carcinoma sequence remain unclear. Here, we profile stool metagenomes obtained from 354 women 12.1 ± 4.8 years following adenoma resection and from their 1:1-matched controls, as well as stool metabolomes from 184 pairs. Metagenomic profiles are compared with those from 14 independent CRC case-control studies. Microbial composition differs between adenoma cases and controls and agrees with CRC-associated alterations (Pearson's rho = 0.26, p < 0.0001). Thirty-one microbes, including Faecalibacterium prausnitzii and Flavonifractor plautii, are altered in both conditions and correlate with lifestyle factors. Thirty metabolites and 7 sub-pathways, particularly sphingolipids, are associated with adenomas. Adenomas also exhibit disease-specific microbe-metabolite associations, including those between Bilophila wadsworthia and alanine-containing dipeptides. These findings reveal gut microbial and metabolomic alterations detectable years after adenoma resection, supporting the presence of an altered microbiome along the adenoma-CRC continuum.

Keywords: adenoma resection; adenoma-carcinoma continuum; colorectal cancer; fecal metabolome; gut microbiome; metagenomics.

MeSH terms

Adenoma* / microbiology
Adenoma* / surgery
Aged
Case-Control Studies
Colorectal Neoplasms* / metabolism
Colorectal Neoplasms* / microbiology
Colorectal Neoplasms* / surgery
Feces* / chemistry
Feces* / microbiology
Female
Gastrointestinal Microbiome*
Humans
Metabolome*
Metagenome
Metagenomics
Middle Aged