Faecal microbiome and metabolic signatures in rectal neuroendocrine tumors

Wei Hu; Ze Min Chen; Xia Xi Li; Lan Lu; Gen Hua Yang; Zheng Xia Lei; Li Juan You; Xiao Bing Cui; Si Cun Lu; Zhi Yong Zhai; Zhi Yu Zeng; Ye Chen; Si Lin Huang; Wei Gong

doi:10.7150/thno.66464

Faecal microbiome and metabolic signatures in rectal neuroendocrine tumors

Theranostics. 2022 Jan 31;12(5):2015-2027. doi: 10.7150/thno.66464. eCollection 2022.

Authors

Wei Hu^{1

2}, Ze Min Chen^{1

2}, Xia Xi Li^{1

2}, Lan Lu³, Gen Hua Yang^{1

2}, Zheng Xia Lei^{1

2}, Li Juan You^{1

2}, Xiao Bing Cui^{1

2}, Si Cun Lu^{1

2}, Zhi Yong Zhai^{1

2}, Zhi Yu Zeng^{1

2}, Ye Chen^{1

2}, Si Lin Huang⁴, Wei Gong^{1

2}

Affiliations

¹ Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China.
² The Third School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong, China.
³ Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, Sichuan, China.
⁴ Department of Gastroenterology, South China Hospital, Health Science Center, Shenzhen University, Shenzhen, Guangdong, China.

Abstract

Background: The prevalence of rectal neuroendocrine tumors (RNET) has increased substantially over the past decades. Little is known on mechanistic alteration in the pathogenesis of such disease. We postulate that perturbations of human gut microbiome-metabolome interface influentially affect the development of RNET. The study aims to characterize the composition and function of faecal microbiome and metabolites in RNET individuals. Methods: We performed deep shotgun metagenomic sequencing and untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomic profiling of faecal samples from the discovery cohort (18 RNET patients, 40 controls), and validated the microbiome and metabolite-based classifiers in an independent cohort (15 RNET participants, 19 controls). Results: We uncovered a dysbiotic gut ecological microenvironment in RNET patients, characterized by aberrant depletion and attenuated connection of microbial species, and abnormally aggregated lipids and lipid-like molecules. Functional characterization based on our in-house and Human Project Unified Metabolic Analysis Network 2 (HUMAnN2) pipelines further indicated a nutrient deficient gut microenvironment in RNET individuals, evidenced by diminished activities such as energy metabolism, vitamin biosynthesis and transportation. By integrating these data, we revealed 291 robust associations between representative differentially abundant taxonomic species and metabolites, indicating a tight interaction of gut microbiome with metabolites in RNET pathogenesis. Finally, we identified a cluster of gut microbiome and metabolite-based signatures, and replicated them in an independent cohort, showing accurate prediction of such neoplasm from healthy people. Conclusions: Our current study is the first to comprehensively characterize the perturbed interface of gut microbiome and metabolites in RNET patients, which may provide promising targets for microbiome-based diagnostics and therapies for this disorder.

Keywords: Gut microbiota; Metabolite; Rectal neuroendocrine tumor; Shotgun metagenomic sequencing; Untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics..

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Gastrointestinal Microbiome*
Humans
Metabolome
Metabolomics / methods
Metagenome
Metagenomics
Microbiota*
Neuroendocrine Tumors*
Tumor Microenvironment