Journal article
Mucosal microbiome markers of complete pathologic response to neoadjuvant therapy in rectal carcinoma
Cancer research communications, Vol.5(5), pp.756-766
05/01/2025
DOI: 10.1158/2767-9764.CRC-25-0036
PMCID: PMC12051095
PMID: 40259625
Abstract
The intestinal microbiome contributes to colorectal carcinogenesis, disease progression, and response to therapy. Pathologic complete response is the therapeutic goal of neoadjuvant chemoradiation in rectal carcinoma. Nonoperative management has become an accepted strategy, and markers of complete treatment response are needed. Intestinal commensal bacteria contribute to treatment response and radiation colitis, and microbiome-targeted therapies have shown promise in clinical trials. We investigated the relationship between mucosa-associated bacteria, neoadjuvant therapy response, and radiation colitis symptoms in 57 patients who received neoadjuvant regimens with no therapy, chemotherapy only, or chemoradiation. The design was a retrospective cohort study. Microbiome profiling was performed by 16S rDNA sequencing of formalin-fixed paraffin-embedded tissue at the proximal margin of resection. Global beta diversity differed according to neoadjuvant therapy modality and was associated with radiation colitis. Taxonomic differences were detectable at phylum and lower classification levels, and radiation-induced colitis was associated with enrichment of the Bacillaceae family. Taxonomic features, including reduced Streptococcus, Lachnospiraceae, and Bacillaceae, were enriched in complete histopathologic responders to neoadjuvant therapy. Taxon-based prediction of metabolic pathways identified enrichment of prokaryotic NAD+ biosynthesis and salvage pathways in complete responders. Mucosal microbiome responses to multimodal neoadjuvant therapy reflect symptomatic radiation colitis, histopathological evidence of radiation injury, and pathologic treatment response. Post-treatment microbiome beta diversity markers of complete pathologic response may be useful in decisions to manage rectal carcinoma non-operatively.
Details
- Title: Subtitle
- Mucosal microbiome markers of complete pathologic response to neoadjuvant therapy in rectal carcinoma
- Creators
- Ibrahim M Abukhiran - University of IowaAmr H Masaadeh - University of IowaJames D Byrne - University of IowaDustin E Bosch - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Cancer research communications, Vol.5(5), pp.756-766
- DOI
- 10.1158/2767-9764.CRC-25-0036
- PMID
- 40259625
- PMCID
- PMC12051095
- NLM abbreviation
- Cancer Res Commun
- ISSN
- 2767-9764
- eISSN
- 2767-9764
- Publisher
- AMER ASSOC CANCER RESEARCH
- Grant note
- University of Iowa Department of PathologyNational Institute of Allergy and Infectious Disease: K08AI159619 NCI of the NIH: P30CA086862 University of Iowa Holden Comprehensive Cancer Center's Gastrointestinal Molecular Epidemiology Resource
This work was supported by a faculty-directed house staff research award (I.M. Abukhiran, A.H. Masaadeh, and D.E. Bosch) from the University of Iowa Department of Pathology and a career development award from the National Institute of Allergy and Infectious Disease (K08AI159619 to D.E. Bosch). The authors thank Dr. Ashutosh Mangalam and the University of Iowa Microbiome Core facility for their assistance with 16S rDNA PCR, library preparation, and sequencing. The authors thank Dr. Carlos Chan and the Biospecimen Procurement and Molecular Epidemiology Resources for providing the fresh frozen colon specimens. The research reported in this publication was supported by the NCI of the NIH under award number P30CA086862. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Research specimens and/or clinical data were obtained from the University of Iowa Holden Comprehensive Cancer Center's Gastrointestinal Molecular Epidemiology Resource, an institutional review board-approved biospecimen repository and data registry (IRB 201202743).
- Language
- English
- Electronic publication date
- 04/21/2025
- Date published
- 05/01/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pathology; Radiation Oncology
- Record Identifier
- 9984813299602771
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