# Dysbiosis-Mediated Regulation of Stem Cells the First Hit for Cancer Generation

**Authors:** Ciro Gargiulo-Isacco, Van Hung Pham, Kieu C. D. Nguyen, Toai C. Tran, Sergey K. Aityan, Raffaele Del Prete, Emilio Jirillo, Luigi Santacroce

PMC · DOI: 10.3390/ijms27020628 · 2026-01-08

## TL;DR

The human microbiota influences cancer development by regulating stem cells through microbial metabolites and signaling molecules.

## Contribution

This paper highlights how microbiota regulates stem cell pathways and contributes to cancer initiation and disease progression.

## Key findings

- Microbial metabolites modulate stem cell pathways like Hedgehog, Wnt/β-catenin, and Notch.
- Specific microbiota taxa in oral, intestinal, and urogenital niches are linked to cancer initiation and therapy resistance.
- Microbiota composition affects infection dynamics with distinct profiles for Gram-positive and Gram-negative strains.

## Abstract

Human microbiota, a complex consortium of microorganisms co-evolved with the host, profoundly influences tissue development, immune regulation, and disease progression. Growing evidence shows that microbial metabolites and signaling molecules modulate key stem cell pathways—such as Hedgehog, Wnt/β-catenin, and Notch—thereby reprogramming stem cell fate toward tumor-suppressive or tumor-promoting outcomes. Specific taxa within oral, intestinal, and urogenital niches have been linked to cancer initiation, therapy resistance, and recurrence. In parallel, clinical studies reveal that microbiota composition affects infection dynamics: bacterial isolates from symptomatic urinary tract infections inhibit commensal growth more strongly than the reverse, with Gram-positive and Gram-negative strains displaying distinct interaction profiles. Collectively, these findings highlight microbiota’s dual role in regulating cellular plasticity and pathogenicity. Elucidating host–microbe and microbe–microbe mechanisms may guide microbiota-targeted interventions to improve cancer and infectious disease management.

## Linked entities

- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}
- **Diseases:** infection (MESH:D007239), urinary tract infections (MESH:D014552), infectious disease (MESH:D003141), Cancer (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12840956/full.md

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Source: https://tomesphere.com/paper/PMC12840956