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Published on: November 5, 2020
Absence of a pancreatic microbiome in intraductal papillary mucinous neoplasm
Marie-Madlen Pust1,2,3, Darío Missael Rocha Castellanos4, Kara Rzasa5
1Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA xavier@molbio.mgh.harvard.edu mpust@mgh.harvard.edu cfernandez@mgh.harvard.edu.
Objective:
This study aims to validate the existence of a microbiome within intraductal papillary mucinous neoplasm (IPMN) that can be differentiated from the taxonomically diverse DNA background of next-generation sequencing procedures.
Design:
We generated 16S rRNA amplicon sequencing data to analyse 338 cyst fluid samples from 190 patients and 19 negative controls, the latter collected directly from sterile syringes in the operating room. A subset of samples (n=20) and blanks (n=5) were spiked with known concentrations of bacterial cells alien to the human microbiome to infer absolute abundances of microbial traces. All cyst fluid samples were obtained intraoperatively and included IPMNs with various degrees of dysplasia as well as other cystic neoplasms. Follow-up culturing experiments were conducted to assess bacterial growth for microbiologically significant signals.
Results:
Microbiome signatures of cyst fluid samples were inseparable from those of negative controls, with no difference in taxonomic diversity, and microbial community composition. In a patient subgroup that had recently undergone invasive procedures, a bacterial signal was evident. This outlier signal was not characterised by higher taxonomic diversity but by an increased dominance index of a gut-associated microbe, leading to lower taxonomic evenness compared with the background signal.
Conclusion:
The 'microbiome' of IPMNs and other pancreatic cystic neoplasms does not deviate from the background signature of negative controls, supporting the concept of a sterile environment. Outlier signals may appear in a small fraction of patients following recent invasive endoscopic procedures. No associations between microbial patterns and clinical or cyst parameters were apparent.
Insights
The microbiome in pancreatic cysts like intraductal papillary mucinous neoplasms (IPMNs) does not differ from sterile controls. Transient bacterial signals may occur after invasive procedures.
Area of Science:
- Gastroenterology
- Microbiology
- Oncology
Background:
- Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cystic neoplasms.
- The presence and nature of a microbiome within IPMNs remain unclear.
- Distinguishing true IPMN microbiomes from sequencing background noise is challenging.
Purpose of the Study:
- To validate the existence of a distinct microbiome within IPMNs.
- To differentiate IPMN-associated microbial signatures from next-generation sequencing background.
- To investigate potential microbial differences in pancreatic cystic neoplasms.
Main Methods:
- 16S rRNA amplicon sequencing of 338 IPMN cyst fluid samples and 19 negative controls.
- Spiking experiments to infer absolute microbial abundances.
- Follow-up culturing to assess bacterial growth.
Main Results:
- IPMN cyst fluid microbiome signatures were indistinguishable from negative controls.
- No significant differences in taxonomic diversity or community composition were observed.
- A small subgroup of patients with recent invasive procedures showed an outlier bacterial signal, characterized by increased dominance of a gut-associated microbe.
Conclusions:
- The 'microbiome' of IPMNs and other pancreatic cystic neoplasms does not differ from background sterile controls.
- Evidence supports a largely sterile environment within these neoplasms.
- Transient bacterial signals may arise post-invasive procedures, but no associations with clinical or cyst parameters were found.
