Blood bacterial DNA, intestinal adenoma and colorectal cancer

Author:

Mutignani MassimilianoORCID,Penagini RobertoORCID,Gargari Giorgio,Guglielmetti Simone,Cintolo Marcello,Airoldi Aldo,Leone Pierfrancesco,Carnevali PietroORCID,Ciafardini Clorinda,Petrocelli Giulio,Mascaretti Federica,Oreggia Barbara,Dioscoridi Lorenzo,Cavalcoli Federica,Primignani Massimo,Pugliese Francesco,Bertuccio PaolaORCID,Soru Pietro,Magistro CarmeloORCID,Ferrari GiovanniORCID,Speciani Michela,Bonato Giulia,Bini Marta,Cantù PaoloORCID,Caprioli Flavio,Vangeli Marcello,Forti Edoardo,Mazza StefanoORCID,Tosetti Giulia,Bonzi RossellaORCID,Vecchi Maurizio,Vecchia Carlo LaORCID,Rossi MartaORCID

Abstract

ABSTRACTObjectiveWe aimed to investigate the relation of blood bacterial DNA load and profiling with intestinal adenoma (IA) and colorectal cancer (CRC) patients.DesignWe performed 16S rRNA gene analysis of blood from 100 incident histologically confirmed CRC cases, 100 IA and 100 healthy subjects, matched to cases by centre, sex and age. Bacterial load was analysed using multiple conditional logistic regression. Differences in terms of abundance of bacteria between groups were estimated through analysis based on negative binomial distribution normalization. Random Forest was applied to predict the group assignment.ResultsWe found an overrepresentation of blood 16S rRNA gene copies in colon cancer as compared to tumor-free controls (IA and healthy subjects). The odds ratio of colon cancer for the highest versus the lowest three quintiles of gene copies was 2.62. (95% confidence interval=1.22-5.65). No difference was found for rectal cancer and IA. For high 16S rRNA, community diversity was higher in colon cancers than controls. CRC cases had an enrichment of Peptostreptococcaceae and Acetobacteriaceae and a reduced abundance of Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae. Identified variables predicted CRC from control and IA patients with an accuracy of 0.70.ConclusionColon cancer patients had a higher DNA bacterial load and a different bacterial profiling as compared to healthy subjects, IA and rectal cancers, indicating a higher passage of bacteria from gastrointestinal tract to bloodstream. Further studies are needed to confirm this result and exploit it to conceive new non-invasive techniques for an early diagnosis of CRC.

Publisher

Cold Spring Harbor Laboratory

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