The Regional Specificity of Mucosa-Associated Microbiota in Patients with Distal Colorectal Cancer

Abstract

<b><i>Background/Aims:</i></b> Recent studies have demonstrated that the populations of several microbes are significantly increased in fecal samples from patients with colorectal cancer (CRC), suggesting their involvement in the development of CRC. The aim of this study was to identify microbes which are increased in distal CRCs and to identify the specific location of microbes increased in mucosal tissue around the tumor. <b><i>Methods:</i></b> Tissue specimens were collected from surgical resections of 28 distal CRCs. Five samples were collected from each specimen (location A: tumor, B: adjacent normal mucosa, C: normal mucosa 1 cm proximal to the tumor, D: normal mucosa 3 cm proximally, and E: normal mucosa 6 cm proximally). The microbiota in the sample were analyzed using 16S rRNA gene amplicon sequencing and the relative abundance (RA) of microbiota compared among the 5 locations. <b><i>Results:</i></b> At the genus level, the RA of <i>Fusobacterium</i> and <i>Streptococcus</i> at location A was the highest among the 5 locations, significantly different from that in location E. The dominant species of each genus was <i>Fusobacterium nucleatum</i> and <i>Streptococcus anginosus.</i> The RAs of these species gradually decreased from locations B to E with a statistically significant difference in <i>F. nucleatum</i>. The genus <i>Peptostreptococcus</i> also showed a similar trend, and the RA of <i>Peptostreptococcus stomatis</i> in location A was significantly associated with depth of tumor invasion and tumor size. <b><i>Conclusion:</i></b> Although the clinical relevance is not clear yet, these results suggest that <i>F. nucleatum, S. anginosus</i>, and <i>P. stomatis</i> can spread to the adjacent normal tissues and may change the surrounding microenvironment to support the progression of CRC.

First reported case of Peptostreptococcus stomatis bacteremia in left orbit apex syndrome patient after dental repair

“…Most of the current studies on P. stomatis have used molecular techniques such as whole-genome sequenced and 16S rRNA gene ampli cation to directly analyze the composition of microbial species in mucosal tissues, feces and other related specimens from patients with oral and gastrointestinal in ammatory diseases and cancer [11]. It is found that there is a higher expression in patients with periodontitis [12], colorectal cancer, gastric cancer, oral cancer and gallbladder cancer, which is considered to be related to the pathogenesis of these diseases [13][14][15][16]. However, it is rare to isolate and culture P.stomatis and carry out routine identi cation and antimicrobial sensitivity test, there is no case report that it causes OAS.…”

Fusobacterium nucleatum and colorectal cancer: From phenomenon to mechanism

“…Likewise, Fn abundance is substantially higher in the tumor than in neighboring normal mucosal tissue from the same individual ( Castellarin et al., 2012 ; Kostic et al., 2012 ; Flanagan et al., 2014 ; Li et al., 2016 ; Gao et al., 2017 ; Yamaoka et al., 2018 ). Interestingly, in the surrounding tissue of CRC, the abundance of Fn is gradually decreased with the distance from the tumor ( Cuellar-Gómez et al., 2021 ; Kono et al., 2021 ). Fn is also positively associated with the progress of CRC.…”