Integrated analysis of microbiome and metabolome reveals signatures in PDAC tumorigenesis and prognosis.

Autor:	Fang Y; Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, China.; National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing, China.; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Liu X; Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, China.; National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing, China.; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Ren J; Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, China.; National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing, China.; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Wang X; Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, China.; National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing, China.; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Zhou F; Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, China.; National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing, China.; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Huang S; Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China., You L; Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, China.; National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing, China.; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Zhao Y; Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, China.; National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing, China.; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Jazyk:	angličtina
Zdroj:	Microbiology spectrum [Microbiol Spectr] 2024 Nov 05; Vol. 12 (11), pp. e0096224. Date of Electronic Publication: 2024 Oct 10.
DOI:	10.1128/spectrum.00962-24
Abstrakt:	Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), is one of the most malignant tumors of the digestive system. Emerging evidence suggests the involvement of the microbiome and metabolic substances in the development of PDAC, yet the results remain contradictory. This study aims to identify the alterations and relationships in intratumoral microbiome and metabolites in PDAC. We collected matched tumor and normal adjacent tissue (NAT) samples from 105 PDAC patients and performed a 6-year follow-up. 2bRAD-M sequencing, untargeted liquid chromatography-tandem mass spectrometry, and untargeted gas chromatography-mass spectrometry were performed. Compared with NATs, microbial α-diversity decreased in PDAC tumors. The relative abundance of Staphylococcus aureus , Cutibacterium acnes, and Cutibacterium granulosum was higher in PDAC tumor after adjusting for confounding factors body mass index and M stage, and the presence of Ralstonia pickettii_B was found associated with a worse overall survival. Metabolomic analysis revealed distinctive differences in composition between PDAC and NAT, with 553 discriminative metabolites identified. Differential metabolites were revealed to originate from the microbiota and showed significant interactions with shifted bacterial species through KO (KEGG Orthology) genes. These findings suggest that the PDAC microenvironment harbors unique microbial-derived enzymatic reactions, potentially influencing the occurrence and development of PDAC by modulating the levels of glycerol-3-phosphate, succinate, carbonate, and beta-alanine. Importance: We conducted a large sample-size pancreatic adenocarcinoma microbiome study using a novel microbiome sequencing method and two metabolomic assays. Two significant outcomes of our analysis are: (i) commensal opportunistic pathogens Staphylococcus aureus , Cutibacterium acnes , and Cutibacterium granulosum were enriched in pancreatic ductal adenocarcinoma (PDAC) tumors compared with normal adjacent tissues, and (ii) worse overall survival was found related to the presence of Ralstonia pickettii_B . Microbial species affect the tumorigenesis, metastasis, and prognosis of PDAC via unique microbe-enzyme-metabolite interaction. Thus, our study highlights the need for further investigation of the potential associations between pancreatic microbiota-derived omics signatures, which may drive the clinical transformation of microbiome-derived strategies toward therapy-targeted bacteria. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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