Abstract: Objective To explore the characteristics of gut microbiota in patients with early-onset colorectal cancer(EOCRC)and its correlation with circulating inflammatory factor profiles.Methods A total of 326 EOCRC patients admitted to the Second Affiliated Hospital of Hunan University of Chinese Medicine from December 2021 to December 2024 were selected as the observation group,and 300 cases of late-onset colorectal cancer(LOCRC)were enrolled as the control group.The levels of high-mobility group box 1(HMGB1),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)were compared between the two groups.Differences in intestinal bacterial counts and and inflammatory factor levels among EOCRC patients with different clinical stages and pathological characteristics(differentiation degree,tumor size,lymphovascular invasion)were analyzed.Pearson correlation analysis was used to examine the correlation between specific gut bacteria and inflammatory cytokines in EOCRC patients.Results Serum levels of HMGB1,IL-6,and TNF-α in the observation group were significantly higher than those in the control group(all P<0.01).The counts of Escherichia coli(E.coli)and Enterococcus faecalis (E.faecalis),as well as the Simpson index,were higher in the observation group,while the counts of Bifidobacterium,Lactobacillus,and Bacteroides,and the Shannon index were lower than those in the control group(all P<0.01).Significant differences in gut microbiota and inflammatory factor levels were observed among EOCRC patients with different clinical stages,differentiation degrees,tumor sizes,and neural/vascular invasion status(all P<0.05).Specifically,EOCRC patients with stage Ⅲ,poor differentiation,tumor diameter >5 cm,and neurovascular invasion exhibited higher counts of E.coli and E.faecalis and higher levels of HMGB1,IL-6,and TNF-α,along with lower counts of Bifidobacterium,Lactobacillus,and Bacteroides(all P<0.05).Pearson correlation analysis showed that E.coli and E.faecalis were positively correlated with serum HMGB1,IL-6,and TNF-α in EOCRC patients,while Bifidobacterium,Lactobacillus,and Bacteroides were negatively correlated with these inflammatory factors(all P<0.01).Conclusion EOCRC patients have significant alterations in gut microbiota structure,and the abundance of specific bacterial is closely related to the spectrum of circulating inflammatory factors.The "microbiota-inflammation" axis is closely related to the clinicopathological characteristics of EOCRC,which can be used as a potential indicator to evaluate the severity of EOCRC and provide a new basis for its individualized treatment.

Key words: early-onset colorectal cancer, gut microbiota, high-mobility group box 1, interleukin-6, tumor necrosis factor-α