Differential effects of commensal bacteria on progenitor cell adhesion, division symmetry and tumorigenesis in the Drosophila intestine

Development. 2021 Mar 9;148(5):dev186106. doi: 10.1242/dev.186106.

Abstract

Microbial factors influence homeostatic and oncogenic growth in the intestinal epithelium. However, we know little about immediate effects of commensal bacteria on stem cell division programs. In this study, we examined the effects of commensal Lactobacillus species on homeostatic and tumorigenic stem cell proliferation in the female Drosophila intestine. We identified Lactobacillus brevis as a potent stimulator of stem cell divisions. In a wild-type midgut, L.brevis activates growth regulatory pathways that drive stem cell divisions. In a Notch-deficient background, L.brevis-mediated proliferation causes rapid expansion of mutant progenitors, leading to accumulation of large, multi-layered tumors throughout the midgut. Mechanistically, we showed that L.brevis disrupts expression and subcellular distribution of progenitor cell integrins, supporting symmetric divisions that expand intestinal stem cell populations. Collectively, our data emphasize the impact of commensal microbes on division and maintenance of the intestinal progenitor compartment.

Keywords: Immunity; Integrins; Intestine; Microbiome; Stem cells; Tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Cell Adhesion*
  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation*
  • Cell Transformation, Neoplastic / drug effects
  • Down-Regulation
  • Drosophila / metabolism*
  • Drosophila / microbiology
  • Drosophila Proteins / deficiency
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Integrins / metabolism
  • Intestines / cytology*
  • Intestines / microbiology
  • Levilactobacillus brevis / drug effects
  • Levilactobacillus brevis / physiology*
  • Receptors, Notch / deficiency
  • Receptors, Notch / genetics
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Stem Cells / microbiology

Substances

  • Anti-Bacterial Agents
  • Drosophila Proteins
  • Integrins
  • N protein, Drosophila
  • Receptors, Notch

Grants and funding