Fecal Microbiota Restoration Modulates the Microbiome in Inflammation-Driven Colorectal Cancer

Abstract

ABSTRACTChronic inflammation of the colon (colitis) is a known risk factor for inflammatory-driven colorectal cancers (idCRC), and intestinal microbiota has been implicated in the etiology of id-CRC. Manipulation of the microbiome is a clinically viable therapeutic approach to limiting id-CRC. To understand the microbiome changes that occur over time in id-CRC, we used a mouse model of idCRC with the treatment of azoxymethane (AOM) and dextran sodium sulfate (DSS) and measured the microbiome over time using 16S rRNA amplicon sequencing. We included cohorts where the microbiome was restored using cage bedding swapping and where the microbiome was depleted using antibiotics to compare to untreated animals. We identified consistent increases inAkkermansiain mice receiving horizontal microbiome transfer (HMT), while the control cohort had consistent longitudinal increases inAnaeroplasmaandAlistipes. Additionally, fecal lipocalin-2 (Lcn-2) concentrations were elevated in unrestored animals compared to restored and antibiotic-treated counterparts following HMT. These observations suggest a potential role forAkkermansia, Anaeroplasma, and Alistipesin regulating colonic inflammation in id-CRC.