Colorectal cancer (CRC) is the most common type cancers in the world. CRC occurs sporadically in the majority of cases, indicating the predominant cause of the disease are environmental factors. Diet-induced changes in gut-microbiome are recently supposed to contribute on epidemics of CRC. This study was aimed to investigate the association of metagenomics and metabolomics in gut extracellular vesicles (EVs) of CRC and healthy subjects. A total of 40 healthy volunteers and 32 patients with CRC were enrolled in this study. Metagenomic profiling by sequencing 16 S rDNA was performed for assessing microbial codiversity. We explored the small molecule metabolites using gas chromatography-time-of-flight mass spectrometry. In total, stool EVs were prepared from 40 healthy volunteers and 32 patients with CRC. Metagenomic profiling demonstrated that bacterial phyla, particularly of Firmicutes and Proteobacteria, were significantly altered in patients with colorectal cancer. Through metabolomics profiling, we determined seven amino acids, four carboxylic acids, and four fatty acids; including short-chain to long chain fatty acids that altered in the disease group. Binary logistic regression was further tested to evaluate the diagnostic performance. In summary, the present findings suggest that gut flora dysbiosis may result in alternation of amino acid metabolism, which may be correlated with the pathogenesis of CRC.Colorectal cancer (CRC) is the most common type cancers in the world 1 . The majority of CRC occurs sporadically, indicating that environmental influences are the predominant cause of the disease 2 . Dietary pattern has long been considered as the most important lifestyle risk factor for CRC. In vivo and in vitro studies have investigated the effect of protein intake on CRC risk and suggest that consumption of excessive protein could lead to DNA damage and influence on the maintenance of colonocyte intergrity 3,4 . Diet-induced changes in gut-microbiome are recently supposed to contribute on epidemics of CRC. Accordingly, studies have suggested that the intestinal microbiome might be important for CRC initiation and progression, since tumors preferentially develop in the distal colon and rectum, which are colonized by approximately 70% of host microbiomes 2,5 . The microbiome has the potential to generate a microenvironment that favors the development of CRC, presumably by recruiting mediators such as interleukins, tumor necrosis factor-alpha, and reactive oxygen species 6,7 . Furthermore, metabolic products of the gut microbiota might increase the risk of developing colorectal cancer. For example, high levels of acetaldehyde produced by the gut microbiota can break down colonial folate, thereby increasing CRC risk 7 .Microbe-derived extracellular vesicles (EVs) are emerging as an important new research subject in understanding the intersection of the gut-microbial communities and human health. Gut microbiota can secrete different types of EVs, including outer membrane vesicles (OMVs), shedding vesicles, and a...

Emerging evidence has suggested that the gut microbiota contribute to brain dysfunction, including pathological symptoms of Alzheimer disease (AD). Microbiota secrete membrane vesicles, also called extracellular vesicles (EVs), which contain bacterial genomic DNA fragments and other molecules and are distributed throughout the host body, including blood. In the present study, we investigated whether bacteria-derived EVs in blood are useful for metagenome analysis in an AD mouse model. Sequence readings of variable regions of 16S rRNA genes prepared from blood EVs in Tg-APP/PS1 mice allowed us to identify over 3,200 operational taxonomic units corresponding to gut microbiota reported in previous studies. Further analysis revealed a distinctive microbiota landscape in Tg-APP/PS1 mice, with a dramatic alteration in specific microbiota at all taxonomy levels examined. Specifically, at the phylum level, the occupancy of p_Firmicutes increased, while the occupancy of p_Proteobacteria and p_Bacteroidetes moderately decreased in Tg-APP/PS1 mice. At the genus level, the occupancy of g_Aerococcus, g_Jeotgalicoccus, g_Blautia, g_Pseudomonas and unclassified members of f_Clostridiale and f_Ruminococcaceae increased, while the occupancy of g_Lactobacillus, unclassified members of f_S24-7, and g_Corynebacterium decreased in Tg-APP/PS1 mice. A number of genus members were detected in Tg-APP/PS1 mice, but not in wild-type mice, while other genus members were detected in wild-type mice, but lost in Tg-APP/PS1 mice. The results of the present study suggest that the bodily microbiota profile is altered in Tg-APP/PS1 mice, and that blood EVs are useful for the metagenome analysis of bodily microbiota in AD.

Colorectal cancer (CRC) is the third most common form of cancer and poses a critical public health threat due to the global spread of westernized diets high in meat, cholesterol, and fat. Although the link between diet and colorectal cancer has been well established, the mediating role of the gut microbiota remains elusive. In this study, we sought to elucidate the connection between the gut microbiota, diet, and CRC through metagenomic analysis of bacteria isolated from the stool of CRC (n = 89) and healthy (n = 161) subjects. This analysis yielded a dozen genera that were significantly altered in CRC patients, including increased Bacteroides, Fusobacterium, Dorea, and Porphyromonas prevalence and diminished Pseudomonas, Prevotella, Acinetobacter, and Catenibacterium carriage. Based on these altered genera, we developed two novel CRC diagnostic models through stepwise selection and a simplified model using two increased and two decreased genera. As both models yielded strong AUC values above 0.8, the simplified model was applied to assess diet-based CRC risk in mice. Mice fed a westernized high-fat diet (HFD) showed greater CRC risk than mice fed a regular chow diet. Furthermore, we found that nonglutinous rice, glutinous rice, and sorghum consumption reduced CRC risk in HFD-fed mice. Collectively, these findings support the critical mediating role of the gut microbiota in diet-induced CRC risk as well as the potential of dietary grain intake to reduce microbiota-associated CRC risk. Further study is required to validate the diagnostic prediction models developed in this study as well as the preventive potential of grain consumption to reduce CRC risk.

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