Julien Terroire
Academic and research departments
Faculty of Engineering and Physical Sciences, School of Biosciences.About
My research project
The Gut Microbiome in Parkinson's Disease and Application of Machine Learning to the Gut MicrobiomeThe gut microbiome is now known to be a player in the development of multiple diseases such as type II diabetes or autism. The gut-brain axis is a strong relationship between the gut microbiome and the brain and could be involved in some neurodegenerative diseases like Parkinson's disease (PD). But for now, this only suspicions. My project aims to identify the microbial communities impacted or involved in the PD development to better understand the disease and its link with the microbial communities of the human gut.
Supervisors
The gut microbiome is now known to be a player in the development of multiple diseases such as type II diabetes or autism. The gut-brain axis is a strong relationship between the gut microbiome and the brain and could be involved in some neurodegenerative diseases like Parkinson's disease (PD). But for now, this only suspicions. My project aims to identify the microbial communities impacted or involved in the PD development to better understand the disease and its link with the microbial communities of the human gut.
Publications
Background: The intra-tumoural microbiome can influence pancreatic tumourigenesis and chemoresistance, and therefore patient survival. The role played by bile microbiota in PDAC is unknown. We aimed to define bile microbiome signatures in patients presenting with obstructive jaundice caused by benign and malignant pancreaticobiliary disease to develop novel cancer biomarkers. Methods: Prospective bile samples were obtained from 37 patients who underwent either endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC). Variable regions (V3–V4) of the 16S rRNA genes were amplified by PCR and next generation sequencing was performed. The cohort consisted of 12 PDAC, 6 cholangiocarcinoma, 10 choledocholithiasis, 7 gallstone pancreatitis and 2 primary sclerosing cholangitis patients. Bile samples from 8 patients were excluded from the analysis because of low read count. Results: Using the 16S rRNA method, we identified a total of 108 genera from 29 individuals (12 PDAC and 17 benign). Bile microbial diversity significantly differed between patients with PDAC vs. benign disease (p=0.0173). The separation of PDAC from benign samples is clearly seen through unsupervised clustering based on Canberra distances. We found 4 genera to be of significantly different abundance between PDAC vs. benign groups by association p-value and supported by false discovery rate (fdr). These were Escherichia, Rothia, Streptococcus and Prevotella. Conclusion: We show that patients with obstructive jaundice caused by PDAC have an altered microbiome composition in the bile, compared to those with benign disease. These bile-based microbes could be developed into potential diagnostic and prognostic biomarkers for PDAC and warrant further investigation.
Pancreatic ductal adenocarcinoma (PDAC) has a very poor survival. The intra-tumoural microbiome can influence pancreatic tumourigenesis and chemoresistance and, therefore, patient survival. The role played by bile microbiota in PDAC is unknown. We aimed to define bile microbiome signatures that can effectively distinguish malignant from benign tumours in patients presenting with obstructive jaundice caused by benign and malignant pancreaticobiliary disease. Prospective bile samples were obtained from 31 patients who underwent either Endoscopic Retrograde Cholangiopancreatography (ERCP) or Percutaneous Transhepatic Cholangiogram (PTC). Variable regions (V3–V4) of the 16S rRNA genes of microorganisms present in the samples were amplified by Polymerase Chain Reaction (PCR) and sequenced. The cohort consisted of 12 PDAC, 10 choledocholithiasis, seven gallstone pancreatitis and two primary sclerosing cholangitis patients. Using the 16S rRNA method, we identified a total of 135 genera from 29 individuals (12 PDAC and 17 benign). The bile microbial beta diversity significantly differed between patients with PDAC vs. benign disease (Permanova p = 0.0173). The separation of PDAC from benign samples is clearly seen through unsupervised clustering of Aitchison distance. We found three genera to be of significantly lower abundance among PDAC samples vs. benign, adjusting for false discovery rate (FDR). These were Escherichia (FDR = 0.002) and two unclassified genera, one from Proteobacteria (FDR = 0.002) and one from Enterobacteriaceae (FDR = 0.011). In the same samples, the genus Streptococcus (FDR = 0.033) was found to be of increased abundance in the PDAC group. We show that patients with obstructive jaundice caused by PDAC have an altered microbiome composition in the bile compared to those with benign disease. These bile-based microbes could be developed into potential diagnostic and prognostic biomarkers for PDAC and warrant further investigation.