Difference Analysis Of Intestinal Microbiome In Patients With Benign And Malignant Breast Tumor

Objective: Intestinal microbiome refer to the microbiome composed of bacteria,fungi,viruses and other microorganisms living in the gastrointestinal tract,which restrict and depend on each other under normal physiological conditions and form a dynamic balance in the body.Recently,the role of gut microbes in health and disease has attracted more and more attention,and many observations and in vitro studies have shown that it may play a role in the occurrence and development of breast cancer.In this paper,the correlation between intestinal microbiome and breast cancer susceptibility was analyzed by comparing intestinal microbiome in patients with benign and malignant tumors.Methods: A total of 102 patients who visited our hospital from January 2019 to December 2020 were included,among whom 19 patients had pathologically confirmed benign breast tumor and 83 patients had pathologically confirmed malignant breast tumor.Stool samples were collected from patients with benign and malignant tumors.DNA was extracted from the two groups of stool samples,respectively,and PCR amplification was performed to establish a library.Illumina sequencing platform was used for sequencing.QIIME software was used for subsequent analysis.Alpha diversity analysis,species composition analysis,beta diversity analysis,functional analysis,and difference analysis were performed between stool samples from patients with benign and malignant tumors.Results: In 102 eligible patients,analysis of DNA sequencing results in stool samples from the benign tumor group and the malignant tumor group showed that there was no significant differences in flora diversity between the two groups.The samples of benign tumor group and malignant tumor were intermingled in the spatial position from the PCo A.And no obvious cluster distribution was expressed,with a P value of 0.956,suggesting that there was no significant difference in the bacteria between the two groups.We further performed species difference analysis and found that a total of 31 significantly different species were discovered at the genus level between benign and malignant tumors: Lefse analysis suggested that there was a significant enrichment of Clostridium,Faecalibacterium,Lachnospira,Erysirobotoutsia,Romboutsia,Fusicatenibacter,Xylophilus,and Arcanobacterium in benign tumors;while enrichment of Citrobacter was observed in malignant tumors.We use STAMP for the third-level KEGG function prediction.We found that 26 pathways such as lipopolysaccharide biosynthesis,cell motility and secretion,folic acid synthesis,biotin metabolism,pore ion channel,glutathione metabolism,D-arginine and D-ornithine metabolism,N-glycan biosynthesis,tricarboxylic acid cycle,and indole alkaloid biosynthesis were significantly different between benign and malignant tumors.Combining with clinical species difference analysis on the factors that may cause bacterial differences between malignant tumors-ER level,PR level,Ki67 status,histological grade suggested that Bacteroides,Bacteroidaceae,Rhodococcus,Opitutales,Hydrogenophilus,and Hydrogenophilaceae were significantly enriched in ER-negative breast cancer;Barnesiellaceae,Lactobacillus,Lactobacillus,Prevotella associated with short-chain fatty acid synthesis,Cloacibacillus,Fixed Bacteria,Haemophilus,Rhodophilaceae,and Haemophilus were enriched in the PR-negative breast cancer group;Ruminiclodium,Chlamydomonas,Flexible Bacteria,Chlorella,Ruminobium,Izimaplasales,Bacillus,Syntrophomonadaceae,and Haemophilus were enriched in the high Ki67 expression group(Ki67 ≥ 30%);Enterobacter,Erysipelotrichaceae,Romboutsia,Anaerostipes,Granulicatella,and Carnobacteriaceae were enriched in the premenopausal breast cancer group;Coriobacteriaceae,Collinsella,and Faecalitalea were enriched in the histological grade III breast cancer group;Megasphaera,Barnesiellaceae,Alloprevotella,Lachnospiraceae,Acinetobacter,Enorma,Flavonifractor,Burkholderiaceae and Eubacterium were enriched in the HER2-positive breast cancer group.Conclusion: The analysis found that a total of 31 significantly different species were found at the level of fecal intestinal microbiome distribution in patients with benign and malignant breast tumors;and 26 different metabolic pathways were significantly different.ER level,PR level,Ki67 status,histological grade and HER2 status can all have a certain impact on the production of differential strains of fecal intestinal microbiome in malignant tumors;these differential strains may be closely related to the occurrence and development of breast cancer,and are expected to be a novel target for the treatment of breast cancer with poor prognosis.