Study Of Probiotics Based On Intestinal Flora And Short-chain Fatty Acid Metabolism To Improve Immune Function In Postoperative Colorectal Cancer Patients

Objective:To investigate the effects of probiotics on intestinal flora,short-chain fatty acid metabolic characteristics and immune function in postoperative patients with colorectal cancer(CRC),and to provide a basis for novel treatment options for colorectal cancer.Methods:This is a prospective,single-blind,randomized controlled study in which Siliankang(Combined Bifidobacterium,Lactobacillus,Enterococcus and Bacillus cereus Tablets,Live.)was selected as a probiotic preparation.Based on the established inclusion and exclusion criteria,100 colorectal cancer patients who underwent radical surgery at the Second Affiliated Hospital of Nanchang University from March 2021to June 2022 were included,and 50 patients were randomly selected as the HOS group(preoperative group,n=50)by the coin flip method,and the patients were randomly divided into the PRO group using the random number table method in the ratio of 1:1(postoperative oral probiotic group,n=50)and CTL group(postoperative oral placebo group,n=50),and patients in both groups were given probiotics and placebo after surgery,respectively.The basic information(name,gender,age),tumor site,pathological findings,and blood was collected for routine blood tests(C-reactive protein,leukocytes,neutrophils,lymphocytes,etc.),blood biochemistry and immune function(CD4~+,CD8~+,CD4~+/CD8~+)before and 7 days after surgery were recorded for each patient.Stool samples were collected from patients in the HOS group before bowel preparation was performed,and the first postoperative stool samples were collected from patients in the CTL and PRO groups at the end of the study and stored at-80°C pending 16S r RNA high-throughput sequencing and GC-MS/MS analysis of short-chain fatty acid concentrations.Results:1.There was no significant difference between the general information of the CTL and HOS groups(P>0.05),and there was no significant difference between the inflammatory indexes(C-reactive protein,leukocytes,neutrophils)and nutritional indexes(albumin)of the two groups before surgery(P>0.05),while on the 7th postoperative day,the inflammatory indexes were significantly higher and nutritional indexes were significantly lower in both groups(P<0.05);and PRO group had significantly lower inflammatory indexes and significantly higher nutritional indexes than the CTL group(P<0.05).2.On postoperative day 7,lymphocytes were reduced compared with admission day 1(P<0.05),while no significant differences were found in CD4~+,CD8~+,and CD4~+/CD8~+(P>0.05)On postoperative day 7,CD4~+,CD4~+/CD8~+,and lymphocytes were higher in the PRO group than in the CTL group,and CD8+was lower than in the CTL group,and the differences were statistically significant(P<0.05).3.Probiotic administration significantly increased the bacterial diversity index of the intestinal flora of CRC patients undergoing radical surgery,increasing the relative abundance of Bacteroidetes,decreasing Fusobacteria,and Proteobacteria at the phylum level.At the genus level,increasing Parabacteroides,Roseburia,and Bacteroides,and decreasing the relative abundance of Lachnospiraceae＿Clostridium genera.4.Probiotics also promoted the production of SCFAs.In patients with postoperative colorectal cancer,the levels of acetic acid,propionic acid,and butyric acid decreased in the HOS and PRO groups,while the levels of acetic acid,propionic acid,and butyric acid increased significantly after probiotic intervention(P<0.05);the levels of isobutyric acid and isovaleric acid decreased after surgery(P<0.05),but probiotic intervention could not increase their levels(P>0.05);hexanoic acid and valeric acid were at low levels in all three groups of samples and no significant differences were seen preoperatively and postoperatively(P>0.05).Conclusion:1.Postoperative patients with colorectal cancer experienced inflammatory reactions,impaired immune function,dysbiosis of intestinal flora and altered metabolism of short-chain fatty acids,decreased beneficial bacteria and increased harmful bacteria,and decreased production of SCFAs acetic acid,propionic acid and butyric acid;2.After taking probiotics in postoperative colorectal cancer patients,the intestinal flora diversity was restored,the relative abundance of probiotics was increased,the colonization of harmful bacteria was reduced,and the production of short-chain fatty acids was promoted,which reduced the inflammatory response and thus enhanced the immune function whose mechanism needs to be further studied.