Related Experiment Video
Updated: Jul 8, 2025
Perturbations of Circulating miRNAs in Irritable Bowel Syndrome Detected Using a Multiplexed High-throughput Gene Expression Platform
Published on: November 30, 2016
Midgut neuroendocrine tumor patients have a depleted gut microbiome with a discriminative signature
M C F Mulders1, A S Audhoe1, P M Van Koetsveld1
1ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus Medical Center and Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands.
Rationale:
When compared to other types of cancer, the prevalence of midgut neuroendocrine tumors (NET) has disproportionally increased over the past decades. To date, there has been very little progress in discovering (epi)genetic drivers and treatment options for these tumors. Recent microbiome research has revealed that enteroendocrine cells communicate with the intestinal microbiome and has provided novel treatment targets for various other cancer types. Hence, our aim was to analyze the role of the gut microbiome in midgut NET patients.
Methods:
Fecal samples, prospectively collected from patients and control subjects, were analyzed with next generation 16S sequencing. Patients with neuroendocrine carcinomas and recent antibiotics use were excluded. Relevant variables were extracted from questionnaires and electronic health records. Microbial composition was compared between patients and controls as well as between groups within the patient cohort.
Results:
87 midgut NET patients and 95 controls were included. Midgut NET patients had a less rich and diverse gut microbiome than controls (p < 0.001). Moreover, we identified 31 differentially abundant species and a gut microbial signature consisting of 17 species that was predictive of midgut NET presence with an area under the receiver operating characteristic curve of 0.863. Gut microbial composition was not directly associated with the presence of the carcinoid syndrome, tumor grade or multifocality. Nonetheless, we did observe a potential link between microbial diversity and the presence of carcinoid syndrome symptoms within the subset of patients with elevated 5-hydroxyindolacetic acid levels.
Conclusion:
Midgut NET patients have an altered gut microbiome which suggests a role in NET development and could provide novel targets for microbiome-based diagnostics and therapeutics.
Insights
Midgut neuroendocrine tumor (NET) patients exhibit altered gut microbiomes, indicating a potential role in tumor development. This discovery opens avenues for novel microbiome-based diagnostics and therapeutics for NET.
Area of Science:
- Gastroenterology
- Oncology
- Microbiome Research
Background:
- Midgut neuroendocrine tumors (NET) show a disproportionate increase in prevalence.
- Limited progress in identifying (epi)genetic drivers and treatments for midgut NET.
- The gut microbiome's role in enteroendocrine cell communication suggests potential therapeutic targets.
Purpose of the Study:
- To investigate the role of the gut microbiome in patients with midgut neuroendocrine tumors.
- To compare the gut microbial composition between midgut NET patients and healthy controls.
Main Methods:
- Analysis of fecal samples using next-generation 16S sequencing.
- Exclusion of patients with neuroendocrine carcinomas and recent antibiotic use.
- Comparison of microbial composition between patient and control groups.
Main Results:
- Midgut NET patients displayed significantly reduced gut microbiome richness and diversity compared to controls (p < 0.001).
- A 17-species gut microbial signature accurately predicted midgut NET presence (AUC = 0.863).
- Microbiome composition was not directly linked to carcinoid syndrome, tumor grade, or multifocality, but diversity showed a potential association with carcinoid syndrome symptoms in a subset of patients.
Conclusions:
- Midgut NET patients possess an altered gut microbiome.
- The gut microbiome may play a role in the development of midgut NET.
- The gut microbiome presents potential targets for novel diagnostic and therapeutic strategies for midgut NET.
