| ObjectiveIn this study,patients with initially treated advanced colorectal cancer who received chemotherapy with CAPEOX regimen were selected as the research objects.By comparing the changes of Fusobacterium nucleatum,Streptococcus,Bifidobacteria and Lactobacillus acidophilus as well as the changes of peripheral blood cytokine levels before and after chemotherapy,we analyze the differences of 4 kinds of specific bacteria and 12 kinds of cytokines in stool in chemotherapy sensitive group and chemotherapy non-sensitive group,gastrointestinal reaction group and no gastrointestinal reaction group respectively,we explore the correlation between intestinal flora and cytokines,chemotherapy efficacy and gastrointestinal reaction.This study provide theoretical basis for further exploring the chemotherapy efficacy and the methods of reducing gastrointestinal reaction by regulating intestinal flora and inflammatory state,and demonstrates broad prospects of searching for potentially valuable therapeutic prediction indicators.MethodsIn this study,40 patients diagnosed with advanced colorectal cancer by pathology were enrolled in the Oncology Department of Qingdao Central Hospital Affiliated to Qingdao University from September 2021 to September 2022.All enrolled patients required CAPEOX chemotherapy according to CSCO guidelines.Fecal samples of enrolled patients were collected within 3 days before chemotherapy and 3 days after the completion of the second cycle of chemotherapy.Peripheral blood was collected at the same time point.Quantitative real-time PCR was used to detect the number of Fusobacterium nucleatum,Streptococcus,Bifidobacteria and Lactobacillus acidophilus in feces,and the changes before and after chemotherapy were compared.Flow cytometry was used to detect cytokines,and its respective changes were compared.The differences of 4specific bacteria and cytokines were compared before and after chemotherapy between chemotherapy sensitive group and chemotherapy non-sensitive group and between groups with and without gastrointestinal reactions.The correlation between the different indexes and the efficacy and adverse reactions was analyzed.Results(1)Changes in the number of specific intestinal flora before and after colorectal cancer chemotherapyAfter colorectal cancer chemotherapy,the number of Fusobacterium nucleatum,Bifidobacteria and Lactobacillus acidophilus in feces decreased significantly,with statistical significance(P<0.01);there was no statistical difference in the number of Streptococcus(P>0.05).(2)Changes of cytokine levels in colorectal cancer before and after chemotherapyThe levels of IL-1β,IL-2,IL-8 and TNF-αwere increased after chemotherapy,with statistical significance(P<0.01);the levels of IL-4 and IL-10 were decreased after chemotherapy,and the differences were statistically significant(P<0.05);the levels of IL-5,IL-6,IL-12 P70,IL-17,IFN-αand IFN-γwere not statistically different.(P>0.05).(3)Differences in the number of specific bacteria in the intestinal tract of patients with colorectal cancer before and after chemotherapy between chemotherapy sensitive group and chemotherapy non-sensitive groupBefore chemotherapy,there was no significant difference in the number of Fusobacterium nucleatum,Streptococcus,Bifidobacterium and Lactobacillus acidophilus between chemotherapy sensitive group and chemotherapy non-sensitive group(P>0.05).After chemotherapy,the number of Fusobacterium nucleatum in chemotherapy sensitive group was significantly lower than that in chemotherapy non-sensitive group,and the difference was statistically significant(P<0.01);The number of intestinal Bifidobacterium in chemotherapy sensitive group was significantly higher than that in chemotherapy non-sensitive group,the difference was statistically significant(P<0.01);there was no significant difference in the number of Streptococcus and Lactobacillus acidophilus between two groups(P>0.05).(4)Difference of cytokine levels in peripheral blood of patients with colorectal cancer before and after chemotherapy between chemotherapy sensitive group and chemotherapy non-sensitive groupBefore chemotherapy,there were no significant differences in the levels of IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12P70,IL-17,TNF-α,IFN-αand IFN-γin peripheral blood between chemotherapy sensitive group and chemotherapy non-sensitive group(P>0.05).After chemotherapy,there was no statistical significance in the above indexes between the two groups(P>0.05).(5)Correlation between specific intestinal bacteria and chemotherapy efficacy in patients with colorectal cancer after chemotherapyCorrelation analysis of different intestinal flora and efficacy between chemotherapy sensitive group and chemotherapy non-sensitive group after chemotherapy showed that the number of Fusobacterium nucleatum was negatively correlated with efficacy(r_s=-0.520,P<0.01),while the number of Bifidobacterium was positively correlated with efficacy(r_s=0.402;P<0.05).(6)Differences in the number of specific intestinal bacteria in patients with colorectal cancer before and after chemotherapy between the gastrointestinal reaction group and the non-gastrointestinal reaction groupThere were no significant differences in the number of Fusobacterium nucleatum,Streptococcus,Bifidobacterium and Lactobacillus acidophilus between the groups with and without gastrointestinal reaction before chemotherapy(P>0.05).After chemotherapy,the number of intestinal Streptococcus,Bifidobacterium and Lactobacillus acidophilus in the group with gastrointestinal reaction was significantly lower than that in the group without gastrointestinal reaction,the difference was statistically significant(P<0.01);there was no significant difference in the number of Fusobacterium nucleatum between the two groups(P>0.05).(7)The difference of cytokine levels in peripheral blood of colorectal cancer patients before and after chemotherapy between gastrointestinal reaction group and no gastrointestinal reaction groupThere were no significant differences in the levels of IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12P70,IL-17,TNF-α,IFN-αand IFN-γin peripheral blood of patients with and without gastrointestinal reaction before chemotherapy(P>0.05).After chemotherapy,the levels of IL-1β,IL-2 and IL-6 in peripheral blood of patients with gastrointestinal reaction were significantly higher than those of patients without gastrointestinal reaction,the differences were statistically significant(P<0.01);the level of IL-10 in the group with gastrointestinal reaction was significantly lower than that in the group without gastrointestinal reaction,the difference was statistically significant(P<0.05);there were no significant differences in IL-4,IL-5,IL-8,IL-12,P70,IL-17,TNF-α,IFN-αand IFN-γ(P>0.05).(8)Association of intestinal specific bacteria and cytokines with gastrointestinal reactions after chemotherapy in patients with colorectal cancerCorrelation analysis of intestinal flora and cytokines with gastrointestinal reactions showed that the number of Streptococcus,Bifidobacterium and Lactobacillus acidophilus were negatively correlated with gastrointestinal reactions(r_s=-0.453,r_s=-0.483,r_s=-0.343;P<0.05).IL-1β,IL-2 and IL-6 were positively correlated with gastrointestinal reactions(r_s=0.556,r_s=0.476,r_s=0.406;P<0.05).IL-10 was negatively correlated with gastrointestinal reactions(r_s=-0.329;P<0.05).Conclusion(1)CAPEOX chemotherapy for colorectal cancer patients reduces the number of intestinal pathogenic bacteria(Fusobacterium nucleatum)and intestinal probiotics(Bifidobacterium and Lactobacillus acidophilus),leading to intestinal flora imbalance and promoting the occurrence of inflammatory response in the body.(2)Patients with colorectal cancer receiving CAPEOX chemotherapy have poor efficacy in patients with a large number of Fusobacterium nucleatum and Bifidobacterium intestinal,while patients with a large number of Bifidobacterium intestinal.Dynamic monitoring of the number of Fusobacterium nucleatum and Bifidobacterium intestinal can help predict the efficacy of chemotherapy,and it is expected to improve the efficacy of chemotherapy through targeted adjustment of intestinal flora.(3)After CAPEOX chemotherapy,colorectal cancer patients with a large number of intestinal probiotics(Streptococcus,Bifidobacterium and Lactobacillus acidophilus)and low inflammatory status had a mild gastrointestinal reaction,while patients with a small number of intestinal probiotics and high inflammatory status had a severe gastrointestinal reaction.It provides a theoretical basis for further exploration of reducing gastrointestinal reactions by adjusting intestinal flora and inflammatory state. |
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