Journal
MSYSTEMS
Volume 4, Issue 5, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/mSystems.00289-19
Keywords
gut microbiome; human stool samples; small RNAs; microRNAs
Categories
Funding
- Italian Institute for Genomic Medicine (IIGM), Italy
- Compagnia di San Paolo Torino, Italy
- Fondazione Umberto Veronesi
- Lega Italiana per La Lotta contro i Tumori
- Grant Agency of the Czech Republic [17-16857S]
- Fondazione CRT [2017.2025]
- Associazione Italiana Celiachia Onlus/Fondazione Celiachia Onlus [015_FC_2017]
- Federazione Italiana Ricerca sul Cancro and Associazione Italiana Ricerca sul Cancro (FIRC-AIRC 2019)
- Fulbright
- Oncobiome European H2020 research project [825410]
- European Research Council [ERC MetaPG-716575]
- H2020 Societal Challenges Programme [825410] Funding Source: H2020 Societal Challenges Programme
Ask authors/readers for more resources
Dysbiotic configurations of the human gut microbiota have been linked to colorectal cancer (CRC). Human small noncoding RNAs are also implicated in CRC, and recent findings suggest that their release in the gut lumen contributes to shape the gut microbiota. Bacterial small RNAs (bsRNAs) may also play a role in carcinogenesis, but their role has been less extensively explored. Here, we performed small RNA and shotgun sequencing on 80 stool specimens from patients with CRC or with adenomas and from healthy subjects collected in a cross-sectional study to evaluate their combined use as a predictive tool for disease detection. We observed considerable overlap and a correlation between metagenomic and bsRNA quantitative taxonomic profiles obtained from the two approaches. We identified a combined predictive signature composed of 32 features from human and microbial small RNAs and DNA-based microbiome able to accurately classify CRC samples separately from healthy and adenoma samples (area under the curve [AUC] = 0.87). In the present study, we report evidence that host-microbiome dysbiosis in CRC can also be observed by examination of altered small RNA stool profiles. Integrated analyses of the microbiome and small RNAs in the human stool may provide insights for designing more-accurate tools for diagnostic purposes. IMPORTANCE The characteristics of microbial small RNA transcription are largely unknown, while it is of primary importance for a better identification of molecules with functional activities in the gut niche under both healthy and disease conditions. By performing combined analyses of metagenomic and small RNA sequencing (sRNA-Seq) data, we characterized both the human and microbial small RNA contents of stool samples from healthy individuals and from patients with colorectal carcinoma or adenoma. With the integrative analyses of metagenomic and sRNA-Seq data, we identified a human and microbial small RNA signature which can be used to improve diagnosis of the disease. Our analysis of human and gut microbiome small RNA expression is relevant to generation of the first hypotheses about the potential molecular interactions occurring in the gut of CRC patients, and it can be the basis for further mechanistic studies and clinical tests.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available