Gut microbial and functional alterations lead to metagenomic signatures for midgut neuroendocrine tumor patients and for carcinoid syndrome

in Endocrine-Related Cancer
Authors:
Merijn C F Mulders ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands

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https://orcid.org/0000-0002-4590-5925
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Peter M Van Koetsveld ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands

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Richard A Feelders ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands

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Leo J Hofland ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands

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https://orcid.org/0000-0002-4897-2197
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Wouter W de Herder ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands

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Robert Kraaij Laboratory of Population Genomics, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

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Johannes Hofland ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands

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https://orcid.org/0000-0003-0679-6209

Correspondence should be addressed to M C F Mulders: m.mulders@erasmusmc.nl

This paper is part of a special collection highlighting the work of emerging leaders in the endocrine cancer field.

DOI:
https://doi.org/10.1530/ERC-24-0145
Volume/Issue:
Volume 32: Issue 2
Article Type:
Research Article
Article ID:
e240145
Online Publication Date:
10 Jan 2025
Copyright:
© the author(s) 2025
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Midgut neuroendocrine tumors (NET) derive from enterochromaffin cells, which have a close interrelationship with intestinal microbiota. Recently, we have utilized 16S rRNA sequencing to uncover that midgut NET patients have a depleted gut microbiome and a specific fecal microbial signature. This study aims to validate these findings and to further characterize the role of microbes and microbial metabolic pathways in midgut NET patients with and without carcinoid syndrome (CS). Fecal samples from 60 midgut NET patients and 20 household-matched controls were subjected to whole metagenome sequencing. The gut microbial community composition of midgut NET patients differed from that of controls, with 2 genera, 17 species and 9 microbial pathways showing differential abundance (P < 0.001). No differences in the microbial composition were observed between midgut NET patients with and without CS (P > 0.05). However, we did observe changes in inter-genus correlations of Bacteroides, Odoribacter, Parasutterella, Klebsiella, Ruminococcus and Proteobacteria when comparing these two patient groups. A signature of 16 microbial species (area under the receiver operating characteristics (AUROC) curve 0.892) or 18 microbial pathways (AUROC 0.909) accurately predicted the presence of a midgut NET. Furthermore, a microbial signature consisting of 14 functional microbial pathways distinguished CS patients from non-CS patients (AUROC 0.807). Thus, this study confirms that the gut microbiome of midgut NET patients is altered at the metagenomic level, which is not related to the presence of CS. A fecal microbial signature could constitute a novel biomarker for the diagnosis of midgut NET or CS.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© the author(s) 2025
Article ID:
e240145
Received Date:
27 Jun 2024
Rev-recd:
08 Nov 2024
Accepted Date:
04 Dec 2024
Print Publication Date:
01 Feb 2025
Online Publication Date:
10 Jan 2025
Keywords:
gut microbiome; neuroendocrine tumor; carcinoid syndrome; diagnosis; biomarkers

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