Microbial and Metabolic Gut Profiling across Seven Malignancies Identifies Fecal and Formic Acid as Commonly Altered in Cancer Patients.

Maria Kulecka, Pawe�� Czarnowski, Aneta Ba��abas, Maryla Turkot, Kamila Kruczkowska-Tarantowicz, Natalia ��eber-Lubecka, Michalina D��browska, Ewa Paszkiewicz-Kozik, Jan Walewski, Iwona ��ugowska, Hanna Kose��a-Paterczyk, Piotr Rutkowski, Anna Kluska, Magdalena Pi��tkowska, Agnieszka Jagie����o-Gruszfeld, Micha�� Tenderenda, Cieszymierz Gawi��ski, Lucjan Wyrwicz, Magdalena Borucka, Maciej Krzakowski, Leszek Zaj��c, Micha�� Kami��ski, Micha�� Mikula, Jerzy Ostrowski
Author Information
  1. Maria Kulecka: Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland.
  2. Pawe�� Czarnowski: Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland. ORCID
  3. Aneta Ba��abas: Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland. ORCID
  4. Maryla Turkot: Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland. ORCID
  5. Kamila Kruczkowska-Tarantowicz: Department of Internal Medicine and Hematology, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, Poland.
  6. Natalia ��eber-Lubecka: Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland.
  7. Michalina D��browska: Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland. ORCID
  8. Ewa Paszkiewicz-Kozik: Department of Lymphoid Malignancies, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
  9. Jan Walewski: Department of Lymphoid Malignancies, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland. ORCID
  10. Iwona ��ugowska: Early Phase Clinical Trials Unit, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
  11. Hanna Kose��a-Paterczyk: Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
  12. Piotr Rutkowski: Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
  13. Anna Kluska: Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
  14. Magdalena Pi��tkowska: Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
  15. Agnieszka Jagie����o-Gruszfeld: Department of Breast Cancer & Reconstructive Surgery, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland. ORCID
  16. Micha�� Tenderenda: Department of Oncological Surgery and Neuroendocrine Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
  17. Cieszymierz Gawi��ski: Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Cancer Research Institute, 02-781 Warsaw, Poland.
  18. Lucjan Wyrwicz: Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Cancer Research Institute, 02-781 Warsaw, Poland.
  19. Magdalena Borucka: Department of Lung and Chest Cancer, Maria Sk��odowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
  20. Maciej Krzakowski: Department of Lung and Chest Cancer, Maria Sk��odowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
  21. Leszek Zaj��c: Department of Gastrointestinal Surgical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
  22. Micha�� Kami��ski: Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland.
  23. Micha�� Mikula: Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland. ORCID
  24. Jerzy Ostrowski: Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland.

Abstract

The key association between gut dysbiosis and cancer is already known. Here, we used whole-genome shotgun sequencing (WGS) and gas chromatography/mass spectrometry (GC/MS) to conduct metagenomic and metabolomic analyses to identify common and distinct taxonomic configurations among 40, 45, 71, 34, 50, 60, and 40 patients with colorectal cancer, stomach cancer, breast cancer, lung cancer, melanoma, lymphoid neoplasms and acute myeloid leukemia (AML), respectively, and compared the data with those from sex- and age-matched healthy controls (HC). ��-diversity differed only between the lymphoid neoplasm and AML groups and their respective HC, while ��-diversity differed between all groups and their HC. Of 203 unique species, 179 and 24 were under- and over-represented, respectively, in the case groups compared with HC. Of these, was under-represented in each of the seven groups studied, was under-represented in all but the stomach cancer group, and 22 species were under-represented in the remaining five case groups. There was a marked reduction in the gut microbiome cancer index in all case groups except the AML group. Of the short-chain fatty acids and amino acids tested, the relative concentration of formic acid was significantly higher in each of the case groups than in HC, and the abundance of seven species of correlated negatively with most amino acids and formic acid, and positively with the levels of acetic, propanoic, and butanoic acid. We found more differences than similarities between the studied malignancy groups, with large variations in diversity, taxonomic/metabolomic profiles, and functional assignments. While the results obtained may demonstrate trends rather than objective differences that correlate with different types of malignancy, the newly developed gut microbiota cancer index did distinguish most of the cancer cases from HC. We believe that these data are a promising step forward in the search for new diagnostic and predictive tests to assess intestinal dysbiosis among cancer patients.

Keywords

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Grants

  1. 2017/27/B/NZ5/01504/National Science Center
  2. 2018/31/B/NZ7/02675/National Science Center
  3. 2020/ABM/01/00004/The Medical Research Agency

MeSH Term

Humans
Gastrointestinal Microbiome
Female
Feces
Male
Formates
Middle Aged
Aged
Neoplasms
Adult
Dysbiosis
Metabolomics
Metabolome
Gas Chromatography-Mass Spectrometry
Metagenomics

Chemicals

Formates
formic acid

Word Cloud

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