AUTHOR=Oliero Manon , Hajjar Roy , Cuisiniere Thibault , Fragoso Gabriela , Calvé Annie , Santos Manuela M. 

TITLE=Inulin impacts tumorigenesis promotion by colibactin-producing Escherichia coli in ApcMin/+ mice

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1067505

DOI=10.3389/fmicb.2023.1067505

ISSN=1664-302X

ABSTRACT=<sec><title>Introduction</title><p>The prebiotic inulin has previously shown both protective and tumor-promoting effects in colorectal cancer (CRC). These inconsistencies may be due to the gut microbial composition as several bacteria have been associated with CRC. Specifically, polyketide synthase-positive (<italic>pks+</italic>) <italic>Escherichia coli</italic> promotes carcinogenesis and facilitates CRC progression through the production of colibactin, a genotoxin that induces double-strand DNA breaks (DSBs). We investigated whether colibactin-producing <italic>Escherichia coli</italic> changed the protection conferred by inulin against tumor growth and progression using the <italic>Apc<sup>Min/+</sup></italic> mouse model of CRC.</p></sec><sec><title>Methods</title><p>Mice received a 2% dextran sodium sulfate (DSS) solution followed by oral gavage with the murine <italic>pks + E. coli</italic> strain NC101 (EcNC101) and were fed a diet supplemented with 10% cellulose as control or 10% inulin for 4 weeks.</p></sec><sec><title>Results</title><p>Inulin supplementation led to increase EcNC101 colonization compared to mice receiving the control diet. The increased colonization of EcNC101 resulted in more DSBs, tumor burden, and tumor progression in <italic>Apc<sup>Min/+</sup></italic> mice. The tumorigenic effect of EcN101 in <italic>Apc<sup>Min/+</sup></italic> mice mediated by inulin was dependent on colibactin production. Pasteurized <italic>E. coli</italic> Nissle 1917 (EcN), a probiotic, suppressed the inulin-driven EcNC101 expansion and impacted tumor progression.</p></sec><sec><title>Discussion</title><p>Our results suggest that the presence of <italic>pks + E. coli</italic> influences the outcome of inulin supplementation in CRC and that microbiota-targeted interventions may mitigate this effect. Given the prevalence of <italic>pks + E. coli</italic> in both healthy and CRC populations and the importance of a fiber-rich diet, inulin supplementation in individuals colonized with <italic>pks +</italic> bacteria should be considered with caution.</p></sec>