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

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 effects of commensal Lactobacillus species on homeostatic, and tumorigenic stem cell growth in the Drosophila intestine. We identified Lactobacillus brevis as a potent stimulator of stem cell growth. In a wildtype midgut, Lactobacillus brevis activates growth regulatory pathways that drive stem cell divisions. In a Notch-deficient background, Lactobacillus brevis-mediated growth causes rapid expansion of mutant progenitors, leading to accumulation of large, multi-layered tumors throughout the midgut. Mechanistically, we showed that Lactobacillus 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 growth and maintenance of the intestinal progenitor compartment.