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Longitudinal changes in the gut microbiota of Vietnamese patients with colorectal cancer undergoing surgery and chemotherapy
Hang Thi Thu Le, Hung Xuan Le, Dao Thi Huyen, Tuan-Anh Tran, Dong Van Quyen, Le Huu Song, Thuan Van Tran, Olivier Thas, Pham Thi Tuyet Nhung, Tam Thi Thanh Tran
Hang Thi Thu Le, Tuan-Anh Tran, Tam Thi Thanh Tran, Department of Life Sciences, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, Hanoi 10000, Viet Nam
Hung Xuan Le, Department of Research Methodology and Biostatistics, Institute of Preventive Medicine and Public Health, Hanoi Medical University, Hanoi 10000, Viet Nam
Hung Xuan Le, Olivier Thas, Data Science Institute, Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, Diepenbeek 3590, Belgium
Dao Thi Huyen, Le Huu Song, Vietnamese-German Center for Medical Research, Hanoi 10000, Viet Nam
Dao Thi Huyen, Le Huu Song, Pham Thi Tuyet Nhung, 108 Military Central Hospital, Hanoi 10000, Viet Nam
Dong Van Quyen, Institute of Biology, Vietnam Academy of Science and Technology, Hanoi 10000, Viet Nam
Thuan Van Tran, National Cancer Hospital and Vietnam National Cancer Institute, Hanoi 10000, Viet Nam
Thuan Van Tran, Pham Thi Tuyet Nhung, Hanoi Medical University, Hanoi 10000, Viet Nam
Co-first authors: Hang Thi Thu Le and Hung Xuan Le.
Co-corresponding authors: Pham Thi Tuyet Nhung and Tam Thi Thanh Tran.
Author contributions: Le HTT and Le HX contributed equally as co-first authors; Nhung PTT and Tran TTT contributed equally as co-corresponding authors; Nhung PTT and Tran TTT contributed to the conceptualization and study design; Le HTT, Huyen DT, Tran TA, Quyen DV, Song LH, Tran TV, Nhung PTT, and Tran TTT contributed to sample collection, methodology, and experimental work; Le HX, Nhung PTT, Thas O, and Tran TTT contributed to data analysis and interpretation; Le HTT, Le HX, Nhung PTT, and Tran TTT drafted the manuscript; all authors reviewed the draft, contributed to editing and approved the submitted version.
Supported by the Vietnam National Foundation for Science and Technology Development, No. 108.04-2021.22.
Institutional review board statement: The study was approved by the Hanoi Medical University Institutional Review Board (Approval No. 503/GCN-HĐĐĐNCYSH-ĐHYHN).
Informed consent statement: All study participants received a thorough explanation of the study’s objectives and signed a written informed consent before inclusion in the study.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: Raw 16S rRNA gene sequencing data are available at the NCBI Sequence Read Archive, under BioProject PRJNA1367939.
Corresponding author: Tam Thi Thanh Tran, PhD, Department of Life Sciences, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Nghia Do Ward, Hanoi 10000, Viet Nam.
tran-thi-thanh.tam@usth.edu.vn
Received: December 30, 2025
Revised: January 22, 2026
Accepted: February 26, 2026
Published online: May 14, 2026
Processing time: 128 Days and 2.4 Hours
BACKGROUND
Colorectal cancer (CRC) is one of the leading common cancers worldwide. Emerging evidence indicates that the gut microbiota influences tumor progression and response to anti-CRC therapies. Yet, longitudinal studies tracking microbiota changes during the treatment period are rare, and none has been conducted in Vietnam.
AIM
To describe gut bacterial diversity and composition changes during CRC treatment, and their association with the response to treatment.
METHODS
Clinical data and fecal samples were obtained from 31 patients with CRC at diagnosis, after surgery, and after chemotherapy completion. After surgery, 13 patients received single-agent therapy [5-fluorouracil (5-FU)] and 18 received combination therapy (≥ 2 drugs, including 5-FU and oxaliplatin). Gut microbial diversity and community composition were characterized using 16S rRNA short-amplicon sequencing (V3-V4) of fecal genomic DNA, followed by downstream analysis with the QIIME2 pipeline.
RESULTS
In patients with CRC, the fecal microbiota alpha and beta diversity (unweighted UniFrac distance) and taxonomic composition changed over time during the treatment period. Alpha diversity decreased after surgery and after chemotherapy compared with baseline (diagnosis), and this was accompanied by the loss of several bacterial families and genera. Several pathogenic taxa, previously identified as overrepresented in patients with CRC relative to healthy individuals, strongly decreased after surgery and after chemotherapy, such as Parvimonas, Peptostreptococcus, Porphyromonas, Desulfovibrio, Prevotella, and Turicibacter. After chemotherapy, short-chain fatty acid-producing bacteria also were reduced, particularly within the genera NK4A214, UCG-005, and UCG-002 (Oscillospiraceae family), as well as the Eubacterium ruminantium and Ruminococcus gauvreauii species. Additionally, several taxa showed differences in function of the chemotherapy regimen and treatment response, which did not remain significant after multiple testing correction.
CONCLUSION
Following surgery and chemotherapy, the gut microbiota profile changed in patients with CRC, with loss of both disease-associated and beneficial bacteria. These results emphasize the potential of microbiota-targeted strategies for improving therapeutic outcomes and quality of life.
Core Tip: Gut microbiota plays key roles in intestinal inflammation and tumor development, but also in shaping the anti-tumor immune responses. We longitudinally monitored the gut microbiota of patients with colorectal cancer (CRC) at diagnosis, after surgery and after chemotherapy. Alpha diversity declined and the overall microbial composition (unweighted UniFrac distance) changed at the three timepoints. Overall, CRC-associated pathogens and short-chain fatty acid-producing bacteria were decreased at post-treatment timepoints. Collectively, these results underscore the clinical potential of microbiota-targeted approaches to strengthen the gut barrier and enhance chemotherapy efficacy.
