Sporamin Intervention Altered the Gut Microbiome and Tumor Tissue Transcriptome in Mice Intraperitoneally Xenografted With the Human Colorectal Carcinoma LoVo Cells

Abstract

BackgroundAccumulating evidence indicates that sporamin, the main storage protein in the sweet potato (Ipomoea batatas), can suppress the development of colorectal cancer (CRC), but the changes in the gut microbiome after sporamin intervention and its relationships with the pathogenesis of CRC have not been investigated.MethodsTwelve male athymic BALB/c nude mice were randomly divided into four groups, CG1, CG2, TCG, and TTG. Mice in TCG and TTG were intraperitoneally transplanted with the LoVo cancer cells before the interventions started. CG2 and TTG were intragastrically infused with sporamin (0.5 g/kg BW/ day) for four weeks while CG1 and TCG were infused with the same volume of water during the experiment. Fecal samples were collected after the interventions and then examined for the changes in the microbiota using the 16S ribosomal RNA (rRNA) sequencing technology. The functional capabilities of the gut microbiota were predicted with the PICRUSt pipeline. Transcriptomic profiling of the tumor tissues was carried out for tumor-bearing mice with the RNA-sequencing (RNA-seq) technology and the resultant differentially expressed genes (DEGs) were then analyzed in terms of gene ontology (GO), protein-protein interaction (PPI), transcription factors (TF) prediction, and biological pathway annotations. ResultsSporamin significantly reduced the tumor burden of tumor-bearing mice and brought beneficial changes to the gut microbiome in both kinds of mice. It significantly increased the proportions of Barnesiella and Lactobacillus but reduced that of Bacteroides in tumor-bearing mice. The phenylalanine metabolism pathway, the glyoxylate, dicarboxylate metabolism, the bacterial secretion system, the glycan biosynthesis and metabolism, and the biosynthesis of stilbenoid, diarylheptanoid, and gingerol were favorably modulated by sporamin intervention. Sporamin mainly modulate the expression of the genes involved in the protein processing in the endoplasmic reticulum, the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway, and the mineral absorption pathway. ConclusionSporamin could favorably alter the gut microbiome and its metabolome, improving the gut microenvironment and the viability of the gut microbiota and increasing the detoxification and bioactive substance production activities in the large intestine, by which the host’s metabolome may be altered and in turn exerts a suppressing effect on the protein synthesis and growth of tumor tissues.