Transcriptomic and Proteomic Study on the High-Fat Diet Combined With AOM/DSS-Induced Adenomatous Polyps in Mice

Abstract

ObjectiveTo screen and identify molecular targets and bacteria genus leading to adenomatous polyps in mouse induced by high-fat diet (HFD) +AOM/DSS using omics technology.MethodsThe molecular targets of colorectal adenoma disease were obtained from the GeneCards and OMIM database. The SPF C57BL mice were randomly divided into blank (Control) and AOM/DSS+HFD colorectal adenoma model (ADH) groups. The ADH model group was intraperitoneally injected with AOM reagent. Then, mice were given with 2.5% DSS (in free drinking water) and high-fat diet to establish the mouse model. During this period, the changes of physical signs of mice in each group were observed. After the end of modeling, HE staining was used to evaluate the histopathological change of mice. The differentially expressed genes and proteins in the Control group and ADH group were detected by RNA-seq transcriptome sequencing and Tandem Mass Tags (TMT) quantitative proteomics. The histological results were analyzed by intersection with the intestinal adenoma molecular targets obtained from the database. Moreover, the changes of intestinal flora in the two groups were examined. The correlation between targets and differential bacteria was analyzed and verified by Parallel Reaction Monitoring (PRM) to comprehensively evaluate the mouse model of adenomatous polyp induced by AOM/DSS+HFD.ResultsThe general condition and histopathological results of mice confirmed that the ADH mouse model was successfully established and tubular adenoma was formed. A total of 604 genes and 42 proteins related to intestinal adenoma were obtained by histological analysis and database intersection analysis. The intestinal microflora of ADH mice was different from that of normal mice, and the constituents and abundance of intestinal flora were similar to those of human intestinal adenoma. GATA4 and LHPP were selected as potential pathological markers of the model mice by correlation analysis of targets and intestinal flora. The results of PRM verification were highly consistent with the results of RNA-Seq transcriptome sequencing and TMT analysis.ConclusionThe pathological results, molecular pathological markers and the changes of intestinal flora suggest that the mouse ADH model is ideal for studying the transformation of inflammatory cancer. The ADH model will be helpful for understanding the occurrence and development of human colorectal cancer at the transcriptomic and proteomic level.

Analysis of the relationship between the gut microbiota enterotypes and colorectal adenoma

“…Clinically, the occurrence of colorectal polyps and adenomas is closely related to dietary habits. Colorectal adenomas occur in patients with relatively control diets or vegetarians, and these patients have a reduced risk of colorectal adenomas ( Guo et al, 2021 ; Nguyen et al, 2021 ). Studies have indicated that enterotypes is related to long-term diet, and the intestinal microbes that cause colorectal adenomas may be different among different enterotypes ( Wu et al, 2011 ).…”

Safety and Efficacy of the Bordetella bronchiseptica Vaccine Combined with a Vegetable Oil Adjuvant and Multi-Omics Analysis of Its Potential Role in the Protective Response of Rabbits

“…Integrating multi-omics analyses is critical to elucidating gene and protein regulation networks from a global viewpoint. Transcriptome and proteome analyses in combination has been widely applied in many research fields, such as human and animal physiology and pathology research [ 57 , 58 , 59 ]. To the best of our knowledge, no studies have reported the use of multi-omics to analyze the effects of vegetable oil adjuvants.…”

Exploring the Mechanism of Action of Canmei Formula Against Colorectal Adenoma Through Multi-Omics Technique

“…This study found that the content of erysipelatoclostridium in ADH mice increased significantly, and CMF could significantly reduce the content of erysipelatoclostridium in the intestine, so it is speculated that Erysipelatoclostridium flora can be a potential pathogenic bacteriain the development of intestinal adenoma. Previous studies showed that Candidatus_Saccharimonas was negatively correlated with LHPP ( Guo et al, 2021 ), and CMF was speculated to play a major role in the anti-CRA effect of Candidatus_Saccharimonas and LHPP, but the relationship between the two is not clear. Further research will be carried out by combining metagenomic sequencing and metabonomics.…”

“…Through clustering and frequency analysis and data mining, our research group found that the core drug for the treatment of CRA was CMF, which consists of Mume Sieb 30 g and Marci Hieronymi 30 g ( Zhang et al, 2019 ). In addition, we successfully established a CRA mouse model induced by high-fat diet in combination with AOM/DSS treatment ( Guo et al, 2021 ). However, at present, the study on CMF remains at the level of overall clinical efficacy, and the mechanism of its action has not been reported, which greatly hindered its promotion and application in clinical practice.…”

“…Therefore, the regulation of intestinal flora plays important roles in the prevention and treatment of intestinal adenoma ( Zhang Y. et al, 2021 ). Traditional Chinese medicine is usually administered orally, and interacts with intestinal flora through the digestive tracts ( Guo et al, 2021 ). Studies have shown that Traditional Chinese medicine exerts therapeutic effects by regulating intestinal flora structure, increasing beneficial bacteria and reducing pathogenic bacteria ( Zhang H.-Y.…”