Dataset Information

Alterations of Gut Mycobiota Profiles in Adenoma and Colorectal Cancer.

ABSTRACT: Accumulating evidence indicates that gut microbiota dysbiosis contributes to colorectal cancer and adenoma. However, a few studies revealed the altered gut mycobiota architecture in colorectal cancer. The present study characterized the gut mycobiota profiles in adenoma and colorectal cancer patients by metagenomic sequencing. Malassezia restricta increased, while Leucoagaricus_sp_SymCcos and fungal_sp_ARF18 significantly decreased in adenoma. Phanerochaete_chrysosporium, Lachancea_waltii, and Aspergillus_rambellii were the top 3 fungi that were significantly enriched in colorectal cancer, while Candida_versatilis, Pseudocercospora_pini_densiflorae, and Candida_sp_JCM_15000 were dominant in the healthy controls. Thirteen fungi, ranked as critical biomarkers in diagnosing colorectal cancer, showed positive associations among all samples. Lachancea_waltii and Phanerochaete_chrysosporium showed the most significant association within CRC. The values of area under the receiver-operating characteristics curve (AUROC) of selected 13 mycobiota were 0.926 in the training model and 0.757 in the 10-fold validation model. Our study provided a reliable investigation of the alterations of gut mycobiota in the development of colorectal cancer and established a convincing diagnostic model for colorectal cancer, which might improve the treatment strategy for colorectal cancer in the future.

SUBMITTER: Gao R

PROVIDER: S-EPMC8908310 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Alterations of Gut Mycobiota Profiles in Adenoma and Colorectal Cancer.

Gao Renyuan R Xia Kai K Wu Minkang M Zhong Hui H Sun Jing J Zhu Yin Y Huang Linsheng L Wu Xiaocai X Yin Lu L Yang Rong R Chen Chunqiu C Qin Huanlong H

Frontiers in cellular and infection microbiology 20220224

Accumulating evidence indicates that gut microbiota dysbiosis contributes to colorectal cancer and adenoma. However, a few studies revealed the altered gut mycobiota architecture in colorectal cancer. The present study characterized the gut mycobiota profiles in adenoma and colorectal cancer patients by metagenomic sequencing. Malassezia restricta increased, while Leucoagaricus_sp_SymCcos and fungal_sp_ARF18 significantly decreased in adenoma. Phanerochaete_chrysosporium< ...[more]

PMID: 35281451

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Project description:BackgroundColorectal cancer is a leading cause of cancer-related deaths worldwide. The human gut microbiome has become an active area of research for understanding the initiation, progression, and treatment of colorectal cancer. Despite multiple studies having found significant alterations in the carriage of specific bacteria within the gut microbiome of colorectal cancer patients, no single bacterium has been unequivocally connected to all cases. Whether alterations in species carriages are the cause or outcome of cancer formation is still unclear, but what is clear is that focus should be placed on understanding changes to the bacterial community structure within the cancer-associated gut microbiome.ResultsBy applying a novel set of analyses on 252 previously published whole-genome shotgun sequenced fecal samples from healthy and late-stage colorectal cancer subjects, we identify taxonomic, functional, and structural changes within the cancer-associated human gut microbiome. Bacterial association networks constructed from these data exhibited widespread differences in the underlying bacterial community structure between healthy and colorectal cancer associated gut microbiomes. Within the cancer-associated ecosystem, bacterial species were found to form associations with other species that are taxonomically and functionally dissimilar to themselves, as well as form modules functionally geared towards potential changes in the tumor-associated ecosystem. Bacterial community profiling of these samples revealed a significant increase in species diversity within the cancer-associated gut microbiome, and an elevated relative abundance of species classified as originating from the oral microbiome including, but not limited to, Fusobacterium nucleatum, Peptostreptococcus stomatis, Gemella morbillorum, and Parvimonas micra. Differential abundance analyses of community functional capabilities revealed an elevation in functions linked to virulence factors and peptide degradation, and a reduction in functions involved in amino-acid biosynthesis within the colorectal cancer gut microbiome.ConclusionsWe utilize whole-genome shotgun sequenced fecal samples provided from a large cohort of late-stage colorectal cancer and healthy subjects to identify a number of potentially important taxonomic, functional, and structural alterations occurring within the colorectal cancer associated gut microbiome. Our analyses indicate that the cancer-associated ecosystem influences bacterial partner selection in the native microbiota, and we highlight specific oral bacteria and their associations as potentially relevant towards aiding tumor progression.

Project description: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.

Project description:The occurrence and development of colorectal cancer (CRC) and advanced adenoma (AA) are closely related to the gut microbiome, and AA has a high cancerization progression rate to CRC. Current studies have revealed that bacteriological analysis cannot identify CRC from AA. The objective was to explore microbial targets that could identify CRC and AA from a microecological perspective and to figure out the best way to identify CRC based on fecal microbes. The metagenomic sequencing data were used to describe the gut microbiome profile and analyze the differences between microbial abundance and microbial single nucleotide polymorphism (SNP) characteristics in AA and CRC patients. It was found that there were no significant differences in the diversity between the two groups. The abundance of bacteria (e.g., Firmicutes, Clostridia, and Blautia), fungi (Hypocreales), archaea (Methanosarcina, Methanoculleus, and Methanolacinia), and viruses (Alphacoronavirus, Sinsheimervirus, and Gammaretrovirus) differed between AA and CRC patients. Multiple machine-learning algorithms were used to establish prediction models, aiming to identify CRC and AA. The accuracy of the random forest (RF) model based on the gut microbiome was 86.54%. Nevertheless, the accuracy of SNP was 92.31% in identifying CRC from AA. In conclusion, using microbial SNP was the best method to identify CRC, it was superior to using the gut microbiome, and it could provide new targets for CRC screening. IMPORTANCE There are differences in characteristic microorganisms between AA and CRC. However, current studies have indicated that bacteriological analysis cannot identify CC from AA, and thus, we wondered if there were some other targets that could be used to identify CRC from AA in the gut microbiome. The differences of SNPs in the gut microbiota of intraindividuals were significantly smaller than those of interindividuals. In addition, compared with intestinal microbes, SNP was less affected by time with certain stability. It was discovered that microbial SNP was better than the gut microbiome for identifying CRC from AA. Therefore, screening characteristic microbial SNP could provide a new research direction for identifying CRC from AA.

Dataset Information

Alterations of Gut Mycobiota Profiles in Adenoma and Colorectal Cancer.

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Alterations of Gut Mycobiota Profiles in Adenoma and Colorectal Cancer.

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