Periodic Reporting for period 4 - ONCOBIOME (Gut OncoMicrobiome Signatures (GOMS) associated with cancer incidence, prognosis and prediction of treatment response.)
Periodo di rendicontazione: 2023-01-01 al 2024-07-31
Beyond its role in regulating multiple physiological functions that impact health, the intestinal metagenome is implicated in cancer initiation, progression and responses to therapies, even for extraintestinal neoplasia. Hence, there is an urgent need to fully identify and functionally characterize minimalist commensal ecosystems relevant to cancer, with reliable and robust methods, to validate cancer-associated gut microbiome fingerprints of high clinical relevance, and to develop diagnosis tools that will become part of the oncological arsenal for the optimization and personalization of therapy. Based on retro-and pro-spective studies, with large discovery and validation cohorts enrolling >5,000 cancer patients across 10 countries, ancillary to ongoing innovative clinical trials or FDA/EMA approvals across 4 frequent cancer types, ONCOBIOME will pursue the following aims: 1/ identify and validate core or cancer-specific Gut OncoMicrobiome Signatures (GOMS) associated with cancer occurrence, prognosis, response to, or progression on, therapy (polychemotherapy, immune checkpoint inhibitors, dendritic cell vaccines) or adverse effects, 2/ decipher the functional relevance of these cancer-associated gut commensal ecosystems in the regulation of host metabolism, immunity and oncogenesis, 3/ integrate these GOMS with other oncology hallmarks (clinics, genomics, immunomics, metabolomics), 4/ design optimal companion tests, based on those integrated signatures to predict cancer occurrence and progression. With high carat interdisciplinary experts, ONCOBIOME expects to validate cancer or therapy-specific Gut OncoMicrobiome Signatures (GOMS) across breast, colorectal, melanoma and lung cancers adjusting for covariates, to unravel the mode of action of these GOMS in innovative platforms, thus lending support to the design of cancer preventive campaigns using well characterized pre-and pro-biotics.
The consortium has made significant progress during this fourth period, beyond expectations.
So far, ONCOBIOME achieved most of its goals while exploiting prospective trials and two national registries. More than 30 cohorts of patients with stage III/IV cancer, either observational or interventional studies based on chemo+/-immuno-therapy, diet, fecal microbiota transplantation (FMT), or live biotherapeutics were investigated prospectively using various omics technologies (including primarily metagenomics and metabolomics). In total, 5,339 cancer patients and 4,535 healthy controls were enrolled allowing stool sequencing of up to 12,059 stool specimens within the ONCOBIOME network.
The partners prepared a Data Sharing and Use Agreement (signed by all parties on September 2023) as the fundamental base to practically centralise the whole consortium clinical and metagenomics data within the web iCloud (CO-DB System). In parallel, the ONCOBIOME consortium investigated the mechanistic links between the intestinal microbiota and cancer immunosurveillance. The Consortium has already published >200 peer-reviewed papers, including in top level journals (Science, Nature Medicine, Cell, etc.). Seventeen publications directly acknowledging ONCOBIOME were issued during P4.
So far, ONCOBIOME achieved most of its goals while exploiting prospective trials and two national registries. More than 30 cohorts of patients with stage III/IV cancer, either observational or interventional studies based on chemo+/-immuno-therapy, diet, fecal microbiota transplantation (FMT), or live biotherapeutics were investigated prospectively using various omics technologies (including primarily metagenomics and metabolomics). In total, 5,339 cancer patients and 4,535 healthy controls were enrolled allowing stool sequencing of up to 12,059 stool specimens within the ONCOBIOME network.
The partners prepared a Data Sharing and Use Agreement (signed by all parties on September 2023) as the fundamental base to practically centralise the whole consortium clinical and metagenomics data within the web iCloud (CO-DB System). In parallel, the ONCOBIOME consortium investigated the mechanistic links between the intestinal microbiota and cancer immunosurveillance. The Consortium has already published >200 peer-reviewed papers, including in top level journals (Science, Nature Medicine, Cell, etc.). Seventeen publications directly acknowledging ONCOBIOME were issued during P4.
The European Union-sponsored ONCOBIOME network has spurred an international effort to identify and validate relevant gut microbiota-related biomarkers in oncology, generating a unique and publicly available microbiome resource. ONCOBIOME explores the effects of the microbiota on gut permeability and metabolism, as well as on antimicrobial and antitumor immune responses. Methods for the diagnosis of gut dysbiosis have been developed based on onco-microbiome signatures associated with the diagnosis, prognosis, and treatment responses in patients with cancer. The mechanisms explaining how dysbiosis compromises natural or therapy-induced immunosurveillance are explored. Through its integrative approach of leveraging multiple cohorts across populations, cancer types and stages, ONCOBIOME has laid the theoretical and practical grounds for the recognition of microbiota alterations as a hallmark of cancer influencing therapy outcome. ONCOBIOME launched microbiota-centered interventions and lobbies in favor of official guidelines for avoiding diet-induced or iatrogenic (e.g. antibiotic- or proton pump inhibitor- induced) dysbiosis.