Parvimonas micra can translocate from the subgingival sulcus of the human oral cavity to colorectal adenocarcinoma

Abstract

Oral and intestinal samples from a cohort of 93 colorectal cancer (CRC) patients and 30 healthy controls (non‐CRC) were collected for microbiome analysis. Saliva (28 non‐CRC and 94 CRC), feces (30 non‐CRC and 97 CRC), subgingival fluid (20 CRC) and tumor tissue samples (20 CRC) were used for 16S metabarcoding and/or RNA sequencing (RNAseq) approaches. A differential analysis of the abundance, performed with the ANCOM‐BC package, adjusting the p‐values by the Holm‐Bonferroni method, revealed that Parvimonas was significantly over‐represented in feces from CRC patients (p‐value <0.001) compared to healthy controls. A total of 11 Parvimonas micra isolates were obtained from the oral cavity and adenocarcinoma of CRC patients. Genome analysis identified a pair of isolates from the same patient that shared 99.2% identity, demonstrating that P. micra can translocate from the subgingival cavity to the gut. The data suggest that P. micra could migrate in a synergistic consortium with other periodontal bacteria. Metatranscriptomics confirmed that oral bacteria were more active in tumor than in non‐neoplastic tissues. We suggest that P. micra could be considered as a CRC biomarker detected in non‐invasive samples such as feces.

Ectopic colonization by oral bacteria as an emerging theme in health and disease

“… 2022 ). Moreover, P. micra was also detected by 16S rRNA gene amplicon sequencing in liver tissue in a patient with liver metastasis, although in this case the authors were unable to isolate the bacterium (Conde-Pérez et al 2023 ). These observations suggest a causal link between invasion of distant places by P. micra and CRC.…”

“…In the past, there have been several studies that have shown an association between ectopic colonization by oral bacteria in the intestinal tract and different intestinal diseases. The most studied phenomenons include IBDs (Atarashi et al 2017 , Dinakaran et al 2019 , Hu et al 2021 ), colorectal cancer (CRC; Castellarin et al 2012 , Flemer et al 2017 , 2018 , Osman et al 2021 , Conde-Pérez et al 2023 ) and childhood undernutrition (Vonaesch et al 2018 , 2022 , Chen et al. 2020 , Collard et al 2022 , Donowitz et al 2022 ).…”

“…Similarly, P. micra is typically found as a commensal with low absolute abundance within the subgingival cavity, respiratory system, and GI tract. However, under certain conditions, it can exhibit opportunistic pathogenic behavior, particularly in the context of periodontal disease (Conde-Pérez et al 2023 ). Recent reports based on 16S rRNA gene amplicon sequencing show that this bacterium is present in higher relative abundance in fecal samples from CRC patients and can be isolated from colonic carcinoma tissue (Osman et al 2021 , Zhao et al 2022 , Bergsten et al.…”

“…qPCR or 16S rRNA amplicon sequencing), and reinforces the need of increasing efforts toward isolating live bacteria to corroborate ectopic colonization. Despite this controversy, most of the studies mentioned in this review pointed out ectopic colonization by oral bacteria in CRC through a combination of metagenomic analysis confirmed by qPCR (Castellarin et al 2012 ), 16S rRNA amplicon sequencing (Flemer et al 2017 , 2018 , Osman et al 2021 ), and direct isolation of the ectopic colonizer strain (Bullman et al 2017 , Conde-Pérez et al 2023 ). Thus, we consider they have provided solid evidence for ectopic colonization by oral bacteria in tumor tissue.…”

“…Despite large efforts directed on understanding the role and function of the human microbiome during the past decades, the causal association between ectopic colonization by oral bacteria and pathophysiology remains poorly understood. Recent literature starts to shed light on the molecular mechanisms that link ectopic colonization by oral bacteria with pathophysiological disturbances such as inflammation (Atarashi et al 2017 , Vonaesch et al 2022 , Bergsten et al 2022 , Conde-Pérez et al 2023 , Miao et al 2023 ), immune system subversion (Bergsten et al 2022 , Conde-Pérez et al 2023 ) or decreased lipid absorption (Vonaesch et al 2022 ). The aim of this review is to provide an overview, summarize and conceptualize the current knowledge about ectopic colonization by oral bacteria and describe its implication in health and disease.…”