International Cancer Microbiome Consortium consensus statement on the role of the human microbiome in carcinogenesis

Abstract

ObjectiveIn this consensus statement, an international panel of experts deliver their opinions on key questions regarding the contribution of the human microbiome to carcinogenesis.DesignInternational experts in oncology and/or microbiome research were approached by personal communication to form a panel. A structured, iterative, methodology based around a 1-day roundtable discussion was employed to derive expert consensus on key questions in microbiome-oncology research.ResultsSome 18 experts convened for the roundtable discussion and five key questions were identified regarding: (1) the relevance of dysbiosis/an altered gut microbiome to carcinogenesis; (2) potential mechanisms of microbiota-induced carcinogenesis; (3) conceptual frameworks describing how the human microbiome may drive carcinogenesis; (4) causation versus association; and (5) future directions for research in the field.The panel considered that, despite mechanistic and supporting evidence from animal and human studies, there is currently no direct evidence that the human commensal microbiome is a key determinant in the aetiopathogenesis of cancer. The panel cited the lack of large longitudinal, cohort studies as a principal deciding factor and agreed that this should be a future research priority. However, while acknowledging gaps in the evidence, expert opinion was that the microbiome, alongside environmental factors and an epigenetically/genetically vulnerable host, represents one apex of a tripartite, multidirectional interactome that drives carcinogenesis.ConclusionData from longitudinal cohort studies are needed to confirm the role of the human microbiome as a key driver in the aetiopathogenesis of cancer.

Alterations of the Predominant Fecal Microbiota and Disruption of the Gut Mucosal Barrier in Patients with Early-Stage Colorectal Cancer

“…In addition, Coker et al also revealed CRCassociated mycobiome dysbiosis characterized by altered fungal composition and ecology, signifying that the gut mycobiome might also play a role in CRC development [5]. Recently, an international panel of experts from International Cancer Microbiome Consortium delivered a consensus statement on the role of the human microbiome in carcinogenesis [17], which emphasized that future studies should provide direct evidence to demonstrate the roles of the human commensal microbiome in the aetiopathogenesis of cancer including CRC.…”

Malnutrition Accelerates Colorectal Cancer Progression through Macrophage Activated by B Cells Immune via Gut Microbiota

“…It brought to our attention that Atopobium and Fusobacterium were identi ed as sarcoidosis-associated bacteria, which may enable new insights into the pathogenesis and treatment of CRC [12]. In CRC, the abundance of Atopobium parvulum and Actinomyces odontolyticus, were signi cantly increased only in multiple polypoid adenomas and/or intramucosal carcinomas, indicating those two bacteria may be considered as the microbiome therapy target in CRC [13]. These studies provided evidence that not only the single effect, but also synergistic effects of Atopobium with other gut microbiota such as Fusobacterium, Stomatobaculum,and Actinomyces may lead to different clinical outcomes.…”

Toxicomicrobiomics: The Human Microbiome vs. Pharmaceutical, Dietary, and Environmental Xenobiotics

“…With any such reported association, a cause-and-effect question is raised: do microbiome variations play a role in disease causation or is it just an association that could merely be used as a biomarker for the adverse health outcome (Maruvada et al, 2017;Rosato et al, 2018). For example, causation has been demonstrated in inflammatory bowel diseases (Moustafa et al, 2018) and colorectal cancer (Tjalsma et al, 2012;Scott et al, 2019).…”

“…Using such biomarkers as non-invasive alternatives to biopsies and endoscopy, for example, would be a promising futuristic diagnostic (Ren et al, 2019) and predictive/preventive tool (Penalver Bernabe et al, 2018). For example, the human microbiota was found to release molecules and metabolites that affect the onset, progression, and treatment of cancer (Scott et al, 2019;Rao et al, 2020). True personalized cancer therapy may only be achieved through a full understanding of the effect of microbiome on chemotherapy (Table 2) and tumorigenesis, thus allowing proper patient stratification-based on specific biomarkers, microbiome types, and metabotypes (Rizkallah et al, 2010;Kuntz and Gilbert, 2017).…”