Pham Thi Tuyet Nhung ^1,2 Hang Thi Thu Le ³ Quang Huy Nguyen ³ Dao Thi Huyen ⁴ Dong Van Quyen ^3,5 Le Huu Song ² Tran Van Thuan ¹ Tam Thi Thanh Tran ^3*

• ¹ Hanoi Medical University, Hanoi, Red River Delta, Vietnam
• ² 108 Hospital, Hanoi, Vietnam
• ³ University of Science and Technology of Hanoi (USTH), Hanoi, Vietnam
• ⁴ Vietnamese - German Center of Excellence in Medical Research, Hanoi, Vietnam
• ⁵ Institute of Biotechnology, Vietnam Academy of Science and Technology, Hanoi, Red River Delta, Vietnam

Background: Colorectal cancer (CRC) is among the top three causes of global cancer-mortality. In Vietnam, CRC is the third leading cause of death in women and the fourth cause of cancer-mortality in men. A large number of metagenomic studies have been reported the relationship between altered composition and function of the gut microbiota with CRC, but this relationship in low and middle-income countries including Vietnam (with an estimated population of 100.3 million people in 2023, ranking 16 th largest country by population in the world) is not well explored.: We collected clinical data and faecal samples from 43 CRC patients and 44 healthy control subjects. Total community DNA of microorganisms was extracted from the faecal samples and analyzed for microbiota composition by Illumina Miseq amplicon sequencing targeting the V3-V4 region of the 16S rRNA gene. Results: We identified a significant difference in the overall faecal microbiota composition between CRC patients and healthy controls, and we detected several CRC-associated microbial signatures in faecal samples of Vietnamese patients with CRC which overlapped with signatures from other countries and meta-analyses. Although the CRC in patients with (n = 8) and without (n = 35) type 2 diabetes (T2D) exhibited distinct gut microbiota composition compared with healthy control, increased relative abundance of putatively pathogenic species including Parvimonas micra, Peptostreptococcus stomatis and Prevotella intermedia were consistent biomarkers for CRC. In contrast, several health-associated species were significantly depleted in CRC patients such as Lactobacillus johnsonii and Bifidobacterium longum in CRC/non-T2D patients, Ruminococcus species, Bacteriodes uniformis and Phascolarctobacterium faecium in CRC/non-T2D patients, and Butyricicoccus pullicaecorum in both CRC groups combined.Vietnamese cohort and highlight several gut microbial taxa that may have inhibitory or driver roles in CRC. This and future studies will be enabled the designing of future cancer diagnostics and treatment strategies for CRC targeting the microbiota in Vietnam.