Gut flora profiling and fecal metabolite composition of colorectal cancer patients and healthy individuals

Wang, Xiaoxue; Wang, Jianping; Rao, Benqiang; Deng, Li

doi:10.3892/etm.2017.4367

Cited by 72 publications

(60 citation statements)

References 31 publications

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“…Enhanced amino acid levels are closely related to CRC risk. Possible reasons for this might include the following: changes in dietary habits, as high protein intake has long been regarded the most important lifestyle risk factor for colorectal cancer 32 ; inflammation, which diminishes the absorption of nutrients in patients with cancer 5,27 ; degradation of dietary protein by fermenting bacteria in the distal colon of patients with CRC, which elevates the levels of amino acid metabolites in stool 16 . One study on amino acid utilization and catabolism in bacteria from the human intestine identified bacteria belonging to the Clostridium clusters (Bacillus, Lactobacillus and some Proteobacteria) as those mostly responsible for the fermentation of amino acids 29 .…”

Section: Discussionmentioning

confidence: 99%

Colorectal cancer diagnostic model utilizing metagenomic and metabolomic data of stool microbial extracellular vesicles

Kim

Yang

Seo³

et al. 2020

Sci Rep

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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...

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Section: Discussionmentioning

confidence: 99%

Colorectal cancer diagnostic model utilizing metagenomic and metabolomic data of stool microbial extracellular vesicles

Kim

Yang

Seo³

et al. 2020

Sci Rep

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“…It is even more desirable to have a paired gut microbiotametabolome data set to dissect the contribution of gut microbiota in metabolomic profiles, as the gut metabolome is derived not only from microbial metabolism but also jointly from diet and host metabolism. So far, in the context of CRC research, there have been only a few studies which globally profiled both gut microbiome and metabolome simultaneously (25)(26)(27). However, all such studies included only CRC patients and controls and lacked patients with adenoma in the study populations.…”

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confidence: 99%

Fecal Metabolomic Signatures in Colorectal Adenoma Patients Are Associated with Gut Microbiota and Early Events of Colorectal Cancer Pathogenesis

Kim

Vogtmann

Ahlquist

et al. 2020

mBio

117

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Colorectal adenomas are precancerous lesions of colorectal cancer (CRC) that offer a means of viewing the events key to early CRC development. A number of studies have investigated the changes and roles of gut microbiota in adenoma and carcinoma development, highlighting its impact on carcinogenesis. However, there has been less of a focus on the gut metabolome, which mediates interactions between the host and gut microbes. Here, we investigated metabolomic profiles of stool samples from patients with advanced adenoma (n = 102), matched controls (n = 102), and patients with CRC (n = 36). We found that several classes of bioactive lipids, including polyunsaturated fatty acids, secondary bile acids, and sphingolipids, were elevated in the adenoma patients compared to the controls. Most such metabolites showed directionally consistent changes in the CRC patients, suggesting that those changes may represent early events of carcinogenesis. We also examined gut microbiome-metabolome associations using gut microbiota profiles in these patients. We found remarkably strong overall associations between the microbiome and metabolome data and catalogued a list of robustly correlated pairs of bacterial taxa and metabolomic features which included signatures of adenoma. Our findings highlight the importance of gut metabolites, and potentially their interplay with gut microbes, in the early events of CRC pathogenesis. IMPORTANCE Colorectal adenomas are precursors of CRC. Recently, the gut microbiota, i.e., the collection of microbes residing in our gut, has been recognized as a key player in CRC development. There have been a number of gut microbiota profiling studies for colorectal adenoma and CRC; however, fewer studies have considered the gut metabolome, which serves as the chemical interface between the host and gut microbiota. Here, we conducted a gut metabolome profiling study of colorectal adenoma and CRC and analyzed the metabolomic profiles together with paired microbiota composition profiles. We found several chemical signatures of colorectal adenoma that were associated with some gut microbes and potentially indicative of future CRC. This study highlights potential early-driver metabolites in CRC pathogenesis and guides further targeted experiments and thus provides an important stepping stone toward developing better CRC prevention strategies.

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“…To date, the most efficient quenching methods immediately suspend the microbial culture in the quenching agent and remove biomass through low‐speed centrifugation or fast‐filtration . Extraction of microbial metabolites is then achieved by the addition of extraction buffer, with or without mechanical microbial cell lysis . Organic solvents are the most commonly applied extraction agents.…”

Section: Investigating the Gut Microbiome With Metabolomicsmentioning

confidence: 99%

“…Metabolomics has become a powerful tool to study the metabolic differences of individuals in healthy and diseased states. Metabolomics on fecal samples from individuals affected by diseases such as IBD and colorectal cancer (CRC) has uncovered interesting metabolic differences when the metabolite profiles are compared to healthy controls. The results obtained from these metabolomic studies, as summarized in Table can give insight into the potential role of microbiome dysbiosis in diseased states and help identify therapeutic targets.…”

Section: Investigating the Gut Microbiome With Metabolomicsmentioning

confidence: 99%

“…Further, Wang et al. also used GC‐MS to study the fecal metabolites of healthy individuals compared to those with CRC . Distinct differences were observed between the two groups, with significantly higher levels of SCFA metabolites (acetic acid, valeric acid, isobutyric acid, and isovaleric acid) and nine amino acids associated with CRC.…”

Section: Investigating the Gut Microbiome With Metabolomicsmentioning

confidence: 99%

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Metaproteomic and Metabolomic Approaches for Characterizing the Gut Microbiome

et al. 2019

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The gut microbiome has been shown to play a significant role in human healthy and diseased states. The dynamic signaling that occurs between the host and microbiome is critical for the maintenance of host homeostasis. Analyzing the human microbiome with metaproteomics, metabolomics, and integrative multi-omics analyses can provide significant information on markers for healthy and diseased states, allowing for the eventual creation of microbiome-targeted treatments for diseases associated with dysbiosis. Metaproteomics enables functional activity information to be gained from the microbiome samples, while metabolomics provides insight into the overall metabolic states affecting/representing the host-microbiome interactions. Combining these functional -omic platforms together with microbiome composition profiling allows for a holistic overview on the functional and metabolic state of the microbiome and its influence on human health. Here the benefits of metaproteomics, metabolomics, and the integrative multi-omic approaches to investigating the gut microbiome in the context of human health and diseases are reviewed.Samples collected from the human gut contains microbiome and host proteins. These microbiome/host proteins directly represent the functional activity of the intestinal ecosystem and can be simultaneously measured by metaproteomics. Metaproteomics can also provide valuable information on the pathways and taxaspecific functions, which provides a more in-depth perspective for studying detailed mechanisms underlying host-microbiome

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Gut flora profiling and fecal metabolite composition of colorectal cancer patients and healthy individuals

Cited by 72 publications

References 31 publications

Colorectal cancer diagnostic model utilizing metagenomic and metabolomic data of stool microbial extracellular vesicles

Colorectal cancer diagnostic model utilizing metagenomic and metabolomic data of stool microbial extracellular vesicles

Fecal Metabolomic Signatures in Colorectal Adenoma Patients Are Associated with Gut Microbiota and Early Events of Colorectal Cancer Pathogenesis

Metaproteomic and Metabolomic Approaches for Characterizing the Gut Microbiome

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