Longitudinal changes in the gut microbiota of Vietnamese patients with colorectal cancer undergoing surgery and chemotherapy

Abstract

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.