Human colon mucosal biofilms from healthy or colon cancer hosts are carcinogenic

Abstract

<p class="first" id="d9303768e433">Mucus-invasive bacterial biofilms are identified on the colon mucosa of approximately 50% of colorectal cancer (CRC) patients and approximately 13% of healthy subjects. Here, we test the hypothesis that human colon biofilms comprise microbial communities that are carcinogenic in CRC mouse models. Homogenates of human biofilm-positive colon mucosa were prepared from tumor patients (tumor and paired normal tissues from surgical resections) or biofilm-positive biopsies from healthy individuals undergoing screening colonoscopy; homogenates of biofilm-negative colon biopsies from healthy individuals undergoing screening colonoscopy served as controls. After 12 weeks, biofilm-positive, but not biofilm-negative, human colon mucosal homogenates induced colon tumor formation in 3 mouse colon tumor models (germ-free <i>Apc ^MinΔ850/+ </i>; <i>Il10 ^–/– </i> or <i>Apc ^MinΔ850/+ </i> and specific pathogen–free <i>Apc ^MinΔ716/+ </i> mice). Remarkably, biofilm-positive communities from healthy colonoscopy biopsies induced colon inflammation and tumors similarly to biofilm-positive tumor tissues. By 1 week, biofilm-positive human tumor homogenates, but not healthy biopsies, displayed consistent bacterial mucus invasion and biofilm formation in mouse colons. 16S rRNA gene sequencing and RNA-Seq analyses identified compositional and functional microbiota differences between mice colonized with biofilm-positive and biofilm-negative communities. These results suggest human colon mucosal biofilms, whether from tumor hosts or healthy individuals undergoing screening colonoscopy, are carcinogenic in murine models of CRC. </p><p class="first" id="d9303768e460"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/6eb66634-d61f-4095-ad4d-9d7484035f46/PubMedCentral/image/jci-129-124196-g229.jpg"/> </div> </p>