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

Abstract

Commensal bacteria regulate the growth and differentiation of intestinal epithelial cells.Deregulated growth compromises the efficacy of critical repair pathways, and promotes tissue dysplasia and tumorigenesis. Despite the importance of bacteria-derived cues for tissue homeostasis, we know little about how intestinal commensals directly influence stem cell division programs. In this study, we examined the effects of common fly symbionts on tissue growth and tumorigenesis in the Drosophila intestine. We identified the cell wall of Lactobacillus brevis as a potent stimulator of Notch-deficient tumor growth. Our work uncovered a complex feed-forward loop between tumor growth and intestinal colonization by L. brevis. Mechanistically, we showed that L. brevis disrupts the expression and apicobasal distribution of integrins in intestinal progenitors, and supports an increase in stem cell numbers characterized by elevated numbers of symmetric stem cell divisions. Collectively, this work highlights host-commensal interactions that influence intestinal growth and stem cell division.

Microbial recognition regulates intestinal epithelial growth in homeostasis and disease

“…Conversely, germ-free Apc min/+ mice have decreased tumor growth, a model dependent on overactive Wnt signaling instead of overt inflammation [104]. Similarly, the microbiome of Drosophila promotes growth of Notchdeficient and BMP-deficient tumors [35,207,208]. These observations suggest the microbiome protects against inflammation-mediated tumorigenesis, while promoting noninflammatory tumor growth.…”

Host-Microbe-Pathogen Interactions: A Review of Vibrio cholerae Pathogenesis in Drosophila

“…For example, IMD is required to survive enteric infections with entemopathogenic Pseudomonas entomophila (122). Additionally, IMD pathway mutants are characterized by changes to the composition of the intestinal microbiome, modified distribution of live bacteria throughout the intestine (123), and elevated bacterial loads in the intestine (17,(123)(124)(125)(126)(127). It is tempting to speculate that IMD controls bacterial populations through the direct release of antimicrobial peptides into the gut lumen.…”

Salmonella enhances osteogenic differentiation in adipose-derived mesenchymal stem cells

“…Though many microbe-host relationships are beneficial to host health and function, pathogenic microbes present currently unknown short and long-term consequences to proximal host cells (O'Rourke and Kempf, 2019). Many stem cells are primed for bacterial interactions and even take cues from association with commensal bacteria (Nigro and Sansonetti, 2015;Ferguson et al, 2021), but the unique proliferation and differentiation properties of stem cells may also make them a target for pathogens looking to evade the immune system and persist long-term (Granick et al, 2012;Jain et al, 2020).…”