Imperial College London
Alternate

ProfessorJulianMarchesi

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor of Digestive Health
 
 
 
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Contact

 

+44 (0)20 3312 6197j.marchesi

 
 
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Location

 

Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Alexander:2023:10.1186/s40168-023-01518-w,
author = {Alexander, J and Posma, J and Scott, A and Poynter, L and Mason, S and Herendi, L and Roberts, L and McDonald, J and Cameron, S and Darzi, A and Goldin, R and Takats, Z and Marchesi, J and Teare, J and Kinross, J},
doi = {10.1186/s40168-023-01518-w},
journal = {Microbiome},
pages = {1--14},
title = {Pathobionts in the tumour microbiota predict survival following resection for colorectal cancer},
url = {http://dx.doi.org/10.1186/s40168-023-01518-w},
volume = {11},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background and aimsThe gut microbiota is implicated in the pathogenesis of colorectal cancer (CRC). We aimed to map the CRC mucosal microbiota and metabolome and define the influence of the tumoral microbiota on oncological outcomes.MethodsA multicentre, prospective observational study was conducted of CRC patients undergoing primary surgical resection in the UK (n = 74) and Czech Republic (n = 61). Analysis was performed using metataxonomics, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), targeted bacterial qPCR and tumour exome sequencing. Hierarchical clustering accounting for clinical and oncological covariates was performed to identify clusters of bacteria and metabolites linked to CRC. Cox proportional hazards regression was used to ascertain clusters associated with disease-free survival over median follow-up of 50 months.ResultsThirteen mucosal microbiota clusters were identified, of which five were significantly different between tumour and paired normal mucosa. Cluster 7, containing the pathobionts Fusobacterium nucleatum and Granulicatella adiacens, was strongly associated with CRC (PFDR = 0.0002). Additionally, tumoral dominance of cluster 7 independently predicted favourable disease-free survival (adjusted p = 0.031). Cluster 1, containing Faecalibacterium prausnitzii and Ruminococcus gnavus, was negatively associated with cancer (PFDR = 0.0009), and abundance was independently predictive of worse disease-free survival (adjusted p = 0.0009). UPLC-MS analysis revealed two major metabolic (Met) clusters. Met 1, composed of medium chain (MCFA), long-chain (LCFA) and very long-chain (VLCFA) fatty acid species, ceramides and lysophospholipids, was negatively associated with CRC (PFDR = 2.61 × 10−11); Met 2, composed of phosphatidylcholine species, nucleosides and amino acids, was strongly associated with CRC (PFDR&
AU  - Alexander,J
AU  - Posma,J
AU  - Scott,A
AU  - Poynter,L
AU  - Mason,S
AU  - Herendi,L
AU  - Roberts,L
AU  - McDonald,J
AU  - Cameron,S
AU  - Darzi,A
AU  - Goldin,R
AU  - Takats,Z
AU  - Marchesi,J
AU  - Teare,J
AU  - Kinross,J
DO  - 10.1186/s40168-023-01518-w
EP  - 14
PY  - 2023///
SN  - 2049-2618
SP  - 1
TI  - Pathobionts in the tumour microbiota predict survival following resection for colorectal cancer
T2  - Microbiome
UR  - http://dx.doi.org/10.1186/s40168-023-01518-w
UR  - https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-023-01518-w
UR  - http://hdl.handle.net/10044/1/103536
VL  - 11
ER  -
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