A conference about relation between gut microbiota and colorectal cancer (CRC) was organized by the Canceropole in Paris this June 28th. Experts presented their studies linking different topics : the host microbiota crosstalk, associations between bacteria and cancer and how microbiota could impact antibiotics and anticancer therapies.
Gerard Eberl from Pasteur Institute started the conference insisting about the importance of microbiota and its potential symbiosis regarding mucosal immunity. Gut microbiota is different among different niches and in case of disease, microbes could take some advantage to growth in specific niche. Host and its microbiota could be seen as a super-organism, a holobiont. There is equilibrium between the microbiota and the host conferring a robust homeostasis. The goal of this seminar is to understand how this equilibrium work. It has been demonstrated that different bacteria have particular interaction with the organism, like for example Bacteroides fragilis and its polysaccharide A but also segmented filamentous bacteria (SFB) which stick to epithelial cells without penetrate it. Gerard Eberl also noticed that gut virus could also play a role to protect the host against pathogens.
Valerie Gaboriau from INRA explained how the balance is complex between bacteria and innate immunity. Delivery mode and diet impacted microbiota on early life. Microbiota became more and more complex until its maturity around 3 years old. The gut microbiota, mainly non cultivable, is composed by two main phyla, Bacteroidetes and Firmicutes. Homeostasis resulted about innate and adaptive immunity. Microbiota established regulation of immune response and barrier against pathogens. Concerning innate defences, the epithelium play a major goal. Valerie Gaboriau describes the epithelium as a sensor, a sampler and a barrier. This barrier is physical, through the mucus, and chemical, through alpha-defensin for example. The sensor ability of epithelium is supported by Toll like receptor localized in the membrane and Nod like receptor localized in the cytoplasm which could be activated by microbial pattern like flagellin for example. The simulation of those receptors induce immune regulation cascade.
Patricia Lepage from INRA, invited us to study the gut microbiome through the prism of meta-omics tools. Metagenomics, metatranscriptomics, metaproteomics and metabolomics are example of approaches to study the human gut microbiota. Those approaches showed for example that the microbiota did not totally recover after many antibiotics courses. The metagenomic approach permitted to establish a useful catalog of 3.3 millions gene of the gut microbiota and to highlight that human shared a core microbiome. With inflammatory bowel disease and cancer for example, the microbiota is destructured and correlation between bacterial species is lost. It appeared that obese patients have less bacterial genes that lean patients. With cancer, it was shown that Fusobacterium, Bacteroides and Escherichia was more prevalent.
Ivo Gomperts Boneca from Pasteur institute comes back to one famous cancer bacterial association: Helicobacter pylori and gastric carcinoma. H. pylori, a major cause of gastroduodenal disease was cultivated for the first time in vitro in 1982. H. pylori notably induce cancer using two ways: 1) induction by CagA protein with oncogenic property and 2) the peptidoglycan translocation requiring a soluble lytic transglucosidase.
Mathias Chamaillard from Pasteur institute described how the triumvirate, composed by microbial dysbiosis, NOD2 and IBD, control the risk the CRC. The gut microbiota control intestinal homeostasis and tumorigenesis. Nod-like receptors are keys for host microbiota crosstalk. Their mutations are implied in a lot of chronic disorders. Using transplantation experiments, it was shown that microbiota from NOD knock out mice drove the disease risk. Furthermore, microbiota transplantation could rescue NOD knock out mice from colitis. The dysbiotic microbial ecology of NOD KO mice is linked with colitis. Mathias Chamaillard concluded saying that faecal transplantation seems to be a promising strategy but need more metabolic characterization.
Shaynoor Dramsi from Pasteur institute talked about the association between Streptococcus gallolyticus and colon cancer. Indeed, this subtype of S. bovis known to be an opportunistic pathogen for infective endocarditis is often associated with CRC. By the way, patients which have an infective endocarditis caused by S. gallolyticus are invited to undergo a colonoscopy to check tumor presence. Except two colonization factors (pil1 and pil3 genes), there is no pathogenic island in the genome of S. gallolyticus. The pil1 operon through his collagen binding domain permits collagen adhesion on epithelial cells. The pil3 operon have a putative mucus binding domain which permit the translocation and S.gallolyticus dissemination.
Eric Oswald from INRA raised the question if Escherichia coli is an enemy inside us. E.coli is one of the first bacteria which colonize new born but become a subdominant bacteria in the rest of life. The pks genes island permit to excrete a genotoxin, the colibactin, preferentially present in E.coli subtype B2. 20% of the newborn are in contact with his subtype. It was shown that E. coli colibactin create DNA damages in newborn enterocyte but that E.coli subtype rapidly decreases over time. In adult age, genotoxic E. coli increase epithelial cells proliferation with more chromosomal instability and cells apoptosis. those studies highlighted the fact that only one bacterial gene could make the difference in the gut ecosystem.
To finish, Romina Goldszmid (Center for Cancer Research, NCI) and Laurence Zitvogel (Institut Gustave Roussy) have focussed on the fact that gut microbiota have to take in account for the therapy and notably chemotherapy for cancer. For example, it was shown that antibiotics which decrease the microbial density in the gut is associated with low efficiency of anti-tumor effect of chemotherapy. In the other side, CTX induces dysbiosis in the small intestine and breaks immune tolerance to gut commensals.