---
title: "Inulin-driven gut microbiome changes increase sporadic colon cancer susceptibility in mice"
id: "biorxiv-8-dietary-fiber-type-specific-gut-microbiome-preconditioning-drives-differential"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-8-dietary-fiber-type-specific-gut-microbiome-preconditioning-drives-differential"
content_type: "clinical_feed_article"
specialty: "Gastroenterology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.21.753221v1?rss=1"
published_at: "2026-09-24T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Inulin-driven gut microbiome changes increase sporadic colon cancer susceptibility in mice
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-8-dietary-fiber-type-specific-gut-microbiome-preconditioning-drives-differential
- **Specialty:** [Gastroenterology](https://medichelpline.com/clinical-feed/gastroenterology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.21.753221v1?rss=1)
- **Published At:** 2026-09-24T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Dietary fiber structure differentially shaped colon tumor outcomes in a mouse AOM model: **inulin** supplementation produced markedly higher tumor rates than other fibers or control. - Experimental design: four-week-old male mice fed low-fiber control or 7.5% (w/w) cellulose, agar, pectin, or inulin diets for 28 weeks with eight intraperitoneal azoxymethane (**AOM**, 7.5 mg/kg) injections. - Outcome: refined inulin supplementation elevated **tumor incidence** to ~70% versus ~10–20% in the other diet groups. - Functional evidence: cecal extracts from inulin-fed, AOM-treated mice increased proliferation of HT29 colorectal cancer cells in vitro. - Microbiome profiling (longitudinal 16S rRNA) identified 36 **inulin-specific microbial signatures** that converged on two functional axes: loss of **short-chain fatty acid (SCFA)** and fermentation cross-feeding taxa, and reprogramming of amino acid and nitrogen metabolism. - Metabolomics (1H-NMR of cecal contents) showed accumulation of succinate, fumarate, and lactate, and depletion of propionate and multiple amino acids — changes observed exclusively in AOM-treated (carcinogen-exposed) mice, not in carcinogen-naive animals. - Network analysis uncovered two stable co-occurrence hubs present only in AOM-treated animals that structurally integrated the fermentation/SCFA axis with the amino-acid/nitrogen metabolism axis. - Interpretation: **inulin** preconditions the gut microbiome toward a functionally vulnerable state (reduced fermentation throughput and altered amino acid metabolism) that, when combined with carcinogen exposure, is amplified into a tumor-promoting ecosystem. - The report is a preprint and has not undergone peer review; authors declared no competing interests.
## Clinical Analysis & Structured Key Points
Dietary fiber-type-specific gut microbiome preconditioning drives differential susceptibility to sporadic colon cancer development | bioRxiv Skip to main content New Results Dietary fiber-type-specific gut microbiome preconditioning drives differential susceptibility to sporadic colon cancer development Sangshan Tian , View ORCID Profile Sumudu Rajakaruna , Gopi Yalavarthi , Umesh K Goand , Tinghua Chen , Won Gu , Justin Silverman , Fuhua Hao , Seth R Bordenstein , Jordan E Bisanz , Amit K Tiwari , Andrew D Patterson , View ORCID Profile Vishal Singh doi: https://doi.org/10.64898/2026.09.21.753221 Sangshan Tian 1 The Pennsylvania State University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Sumudu Rajakaruna 1 The Pennsylvania State University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sumudu Rajakaruna Gopi Yalavarthi 1 The Pennsylvania State University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Umesh K Goand 1 The Pennsylvania State University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Tinghua Chen 1 The Pennsylvania State University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Won Gu 1 The Pennsylvania State University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Justin Silverman 1 The Pennsylvania State University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Fuhua Hao 1 The Pennsylvania State University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Seth R Bordenstein 1 The Pennsylvania State University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jordan E Bisanz 1 The Pennsylvania State University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Amit K Tiwari 2 University of Arkansas for Medical Sciences Find this author on Google Scholar Find this author on PubMed Search for this author on this site Andrew D Patterson 1 The Pennsylvania State University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Vishal Singh 1 The Pennsylvania State University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Vishal Singh For correspondence: vxs28{at}psu.edu Abstract Info/History Metrics Supplementary material Preview PDF Abstract Background: Dietary fiber intake is broadly associated with reduced colorectal cancer (CRC) risk, yet processed fiber supplements exert inconsistent and occasionally opposing effects on colon tumorigenesis. How structurally distinct dietary fibers differentially shape the gut microbiome-metabolome axis to influence carcinogenic susceptibility remains poorly understood. Objective: To determine whether structurally distinct dietary fibers differentially modulate colon tumor development and characterize the underlying gut microbiome and metabolic mechanisms. Design: Four-week-old male mice were maintained on low-fiber control or fiber-supplemented diets (7.5%w/w: cellulose, agar, pectin, or inulin) for 28 weeks and received eight intraperitoneal azoxymethane injections (AOM; 7.5 mg/kg). Temporal fecal microbiomes were profiled by 16S-rRNA sequencing, cecal metabolites quantified by H-NMR spectroscopy, and microbiome-metabolome interactions assessed by co-occurrence networks. Results: Refined inulin supplementation markedly elevated colon tumor incidence (~70%) compared with all other groups (~10-20%), and cecal extracts from inulin-fed mice promoted HT29 cancer-cell proliferation. Longitudinal microbiome profiling identified 36 inulin-specific microbial signatures converging on two axes: depletion of SCFAs and fermentation cross-feeding taxa and reprogramming of amino acid and nitrogen metabolism. Metabolomics confirmed succinate, fumarate, and lactate accumulation alongside propionate and amino acid depletion exclusively under AOM conditions, with no differences in carcinogen-naive animals. Two stable co-occurrence hubs were identified exclusively in AOM-treated animals, structurally integrating both functional axes. Conclusion: Inulin supplementation preconditions the gut microbiome toward functional vulnerability, characterized by disrupted fermentation throughput and reprogrammed amino acid metabolism, that is amplified by carcinogen exposure into a tumor-promoting ecosystem, providing a mechanistic basis for the disproportionately higher tumor prevalence in inulin-fed animals. Competing Interest Statement The authors have declared no competing interest. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license . Back to top Previous Next Posted September 24, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Dietary fiber-type-specific gut microbiome preconditioning drives differential susceptibility to sporadic colon cancer development Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Dietary fiber-type-specific gut microbiome preconditioning drives differential susceptibility to sporadic colon cancer development Sangshan Tian , Sumudu Rajakaruna , Gopi Yalavarthi , Umesh K Goand , Tinghua Chen , Won Gu , Justin Silverman , Fuhua Hao , Seth R Bordenstein , Jordan E Bisanz , Amit K Tiwari , Andrew D Patterson , Vishal Singh bioRxiv 2026.09.21.753221; doi: https://doi.org/10.64898/2026.09.21.753221 Share This Article: Copy Citation Tools Dietary fiber-type-specific gut microbiome preconditioning drives differential susceptibility to sporadic colon cancer development Sangshan Tian , Sumudu Rajakaruna , Gopi Yalavarthi , Umesh K Goand , Tinghua Chen , Won Gu , Justin Silverman , Fuhua Hao , Seth R Bordenstein , Jordan E Bisanz , Amit K Tiwari , Andrew D Patterson , Vishal Singh bioRxiv 2026.09.21.753221; doi: https://doi.org/10.64898/2026.09.21.753221 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8025) Biochemistry (18803) Bioengineering (14932) Bioinformatics (44519) Biophysics (22647) Cancer Biology (19785) Cell Biology (26960) Clinical Trials (138) Developmental Biology (14000) Ecology (21056) Epidemiology (2067) Evolutionary Biology (25500) Genetics (16189) Genomics (23540) Immunology (18737) Microbiology (42585) Molecular Biology (18115) Neuroscience (93664) Paleontology (701) Pathology (2989) Pharmacology and Toxicology (5106) Physiology (8134) Plant Biology (16034) Scientific Communication and Education (2098) Synthetic Biology (4575) Systems Biology (10258) Zoology (2393)
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