Vitamin A deficiency (VAD) plays an essential role in the pathogenesis of Alzheimer’s disease (AD). However, the specific mechanism by which VAD aggravates cognitive impairment is still unknown. At the intersection of microbiology and neuroscience, the gut-brain axis is undoubtedly contributing to the formation and function of neurological systems, but most of the previous studies have ignored the influence of gut microbiota on the cognitive function in VAD. Therefore, we assessed the effect of VAD on AD pathology and the decline of cognitive function in AD model mice and determined the role played by the intestinal microbiota in the process. Twenty 8-week-old male C57BL/6J amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice were randomly assigned to either a vitamin A normal (VAN) or VAD diet for 45 weeks. Our results show that VAD aggravated the behavioral learning and memory deficits, reduced the retinol concentration in the liver and the serum, decreased the transcription of vitamin A (VA)-related receptors and VA-related enzymes in the cortex, increased amyloid-β peptides (Aβ40 and Aβ42) in the brain and gut, upregulate the translation of beta-site APP-cleaving enzyme 1 (BACE1) and phosphorylated Tau in the cortex, and downregulate the expression of brain-derived neurotrophic factor (BDNF) and γ-aminobutyric acid (GABA) receptors in the cortex. In addition, VAD altered the composition and functionality of the fecal microbiota as exemplified by a decreased abundance of Lactobacillus and significantly different α- and β-diversity. Of note, the functional metagenomic prediction (PICRUSt analysis) indicated that GABAergic synapse and retinol metabolism decreased remarkably after VAD intervention, which was in line with the decreased expression of GABA receptors and the decreased liver and serum retinol. In summary, the present study provided valuable facts that VAD exacerbated the morphological, histopathological, molecular biological, microbiological, and behavioral impairment in the APP/PS1 transgenic mice, and the intestinal microbiota may play a key mediator role in this mechanism.

Sporamin, a proteinase inhibitor isolated from the sweet potato (Ipomoea batatas), has shown promising anticancer effect against colorectal cancer (CRC) in vitro and in vivo but its mechanisms of action are poorly understood. In the present study, high throughput RNA sequencing (RNA-seq) technology was applied to explore the transcriptomic changes induced by sporamin in the presence of thapsigargin (TG), a non-12-O-tetradecanolphorbol-13-acetate type cancer promoter, in the LoVo human CRC cells. Cellular total RNA was extracted from the cells after they were treated with vehicle (CTL), 1 μM of thapsigargin (TG), or 1 μM of TG plus 30 μM of sporamin (TGSP) for 24 h. The migratory capacity of the cells was determined by wound healing assay. The gene expression profiles of the cells were determined by RNA-seq on an Illumina platform. GO enrichment analysis, KEGG pathway analysis, protein-protein interaction (PPI) network construction, and transcription factors (TF) prediction were all performed based on the differentially expressed genes (DEGs) across groups with a series of bioinformatics tools. Finally, the effect and potential molecular targets of the sporamin at the transcriptome level were evaluated. Sporamin significantly inhibited the migration of cells induced by TG. Among the 17915 genes detected in RNA-seq, 46 DEGs were attributable to the effect of sporamin. RT-PCR experiment validated that the expression of RGPD2, SULT1A3, and BIVM-ERCC5 were up-regulated while NYP4R, FOXN1, PAK6, and CEACAM20 were down-regulated. Sporamin enhanced the mineral absorption pathway, worm longevity regulating pathway, and pyrimidine metabolism pathway. Two TFs (SMIM11A and ATOH8) were down-regulated by sporamin. HMOX1 (up-regulated) and NME1-NME2 (down-regulated) were the main nodes in a PPI network consisting of 16 DEGs that were modulated by sporamin in the presence of TG. Sporamin could favorably alter the gene expression profile of CRC cells, up-regulating the genes that contribute to the homeostasis of intracellular metal ions and the activities of essential enzymes and DNA damage repairment. More studies are warranted to verify its effect on specific genes and delineate the mechanism of action implicated in the process.

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.