Interactions of Segmented Filamentous Bacteria (Candidatus Savagella) and bacterial drivers in colitis-associated colorectal cancer development.

Abstract

Colorectal cancer (CRC) risk is influenced by host genetics, sex, and the gut microbiota. Using a genetically susceptible mouse model of CRC induced via inoculation with pathobiont Helicobacter spp. and demonstrating variable tumor incidence, we tested the ability of the Th17-enhancing commensal Candidatus Savagella, more commonly denoted as Segmented Filamentous Bacteria (SFB), to influence the incidence and severity of colitis-associated CRC in male and female mice. To document the composition of the gut microbiota during CRC development and identify taxa associated with disease, fecal samples were collected before and throughout disease development and characterized via 16S rRNA sequencing. While there were no significant SFB-dependent effects on disease incidence or severity, SFB was found to exert a sex-dependent protective effect in male mice. Furthermore, SFB stabilized the GM against Helicobacter-induced changes post-inoculation, resulting in a shift in disease association from Helicobacter spp. to Escherichia coli. These data support sex-dependent SFB-mediated effects on CRC risk, and highlight the complex community dynamics within the GM during exposure to inflammatory pathobionts.