Fecal Metabolomic Signatures in Colorectal Adenoma Patients Are Associated with Gut Microbiota and Early Events of Colorectal Cancer Pathogenesis
ABSTRACT 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 carci...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2020-02-01
|
| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.03186-19 |
| _version_ | 1818424681622929408 |
|---|---|
| author | Minsuk Kim Emily Vogtmann David A. Ahlquist Mary E. Devens John B. Kisiel William R. Taylor Bryan A. White Vanessa L. Hale Jaeyun Sung Nicholas Chia Rashmi Sinha Jun Chen |
| author_facet | Minsuk Kim Emily Vogtmann David A. Ahlquist Mary E. Devens John B. Kisiel William R. Taylor Bryan A. White Vanessa L. Hale Jaeyun Sung Nicholas Chia Rashmi Sinha Jun Chen |
| author_sort | Minsuk Kim |
| collection | DOAJ |
| description | ABSTRACT 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. |
| first_indexed | 2024-12-14T14:01:55Z |
| format | Article |
| id | doaj.art-4c9dce8970ac4103b3c5282d6a0dfa44 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-14T14:01:55Z |
| publishDate | 2020-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-4c9dce8970ac4103b3c5282d6a0dfa442022-12-21T22:58:42ZengAmerican Society for MicrobiologymBio2150-75112020-02-0111110.1128/mBio.03186-19Fecal Metabolomic Signatures in Colorectal Adenoma Patients Are Associated with Gut Microbiota and Early Events of Colorectal Cancer PathogenesisMinsuk Kim0Emily Vogtmann1David A. Ahlquist2Mary E. Devens3John B. Kisiel4William R. Taylor5Bryan A. White6Vanessa L. Hale7Jaeyun Sung8Nicholas Chia9Rashmi Sinha10Jun Chen11Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USAMetabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USADivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USADivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USADivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USADivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USACarl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USAMicrobiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USAMicrobiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USAMicrobiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USAMetabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USAMicrobiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.03186-19carcinogenesiscolorectal adenomacolorectal cancermetabolomicsmicrobiomemicrobiota |
| spellingShingle | Minsuk Kim Emily Vogtmann David A. Ahlquist Mary E. Devens John B. Kisiel William R. Taylor Bryan A. White Vanessa L. Hale Jaeyun Sung Nicholas Chia Rashmi Sinha Jun Chen Fecal Metabolomic Signatures in Colorectal Adenoma Patients Are Associated with Gut Microbiota and Early Events of Colorectal Cancer Pathogenesis mBio carcinogenesis colorectal adenoma colorectal cancer metabolomics microbiome microbiota |
| title | Fecal Metabolomic Signatures in Colorectal Adenoma Patients Are Associated with Gut Microbiota and Early Events of Colorectal Cancer Pathogenesis |
| title_full | Fecal Metabolomic Signatures in Colorectal Adenoma Patients Are Associated with Gut Microbiota and Early Events of Colorectal Cancer Pathogenesis |
| title_fullStr | Fecal Metabolomic Signatures in Colorectal Adenoma Patients Are Associated with Gut Microbiota and Early Events of Colorectal Cancer Pathogenesis |
| title_full_unstemmed | Fecal Metabolomic Signatures in Colorectal Adenoma Patients Are Associated with Gut Microbiota and Early Events of Colorectal Cancer Pathogenesis |
| title_short | Fecal Metabolomic Signatures in Colorectal Adenoma Patients Are Associated with Gut Microbiota and Early Events of Colorectal Cancer Pathogenesis |
| title_sort | fecal metabolomic signatures in colorectal adenoma patients are associated with gut microbiota and early events of colorectal cancer pathogenesis |
| topic | carcinogenesis colorectal adenoma colorectal cancer metabolomics microbiome microbiota |
| url | https://journals.asm.org/doi/10.1128/mBio.03186-19 |
| work_keys_str_mv | AT minsukkim fecalmetabolomicsignaturesincolorectaladenomapatientsareassociatedwithgutmicrobiotaandearlyeventsofcolorectalcancerpathogenesis AT emilyvogtmann fecalmetabolomicsignaturesincolorectaladenomapatientsareassociatedwithgutmicrobiotaandearlyeventsofcolorectalcancerpathogenesis AT davidaahlquist fecalmetabolomicsignaturesincolorectaladenomapatientsareassociatedwithgutmicrobiotaandearlyeventsofcolorectalcancerpathogenesis AT maryedevens fecalmetabolomicsignaturesincolorectaladenomapatientsareassociatedwithgutmicrobiotaandearlyeventsofcolorectalcancerpathogenesis AT johnbkisiel fecalmetabolomicsignaturesincolorectaladenomapatientsareassociatedwithgutmicrobiotaandearlyeventsofcolorectalcancerpathogenesis AT williamrtaylor fecalmetabolomicsignaturesincolorectaladenomapatientsareassociatedwithgutmicrobiotaandearlyeventsofcolorectalcancerpathogenesis AT bryanawhite fecalmetabolomicsignaturesincolorectaladenomapatientsareassociatedwithgutmicrobiotaandearlyeventsofcolorectalcancerpathogenesis AT vanessalhale fecalmetabolomicsignaturesincolorectaladenomapatientsareassociatedwithgutmicrobiotaandearlyeventsofcolorectalcancerpathogenesis AT jaeyunsung fecalmetabolomicsignaturesincolorectaladenomapatientsareassociatedwithgutmicrobiotaandearlyeventsofcolorectalcancerpathogenesis AT nicholaschia fecalmetabolomicsignaturesincolorectaladenomapatientsareassociatedwithgutmicrobiotaandearlyeventsofcolorectalcancerpathogenesis AT rashmisinha fecalmetabolomicsignaturesincolorectaladenomapatientsareassociatedwithgutmicrobiotaandearlyeventsofcolorectalcancerpathogenesis AT junchen fecalmetabolomicsignaturesincolorectaladenomapatientsareassociatedwithgutmicrobiotaandearlyeventsofcolorectalcancerpathogenesis |