The Third International Congress of Translational Research in Human Nutrition (#ICTRHN2015) took place in Clermont-Ferrand, France, on June 26 & 27, 2015.
In this post, we bring you the highlights of the event introduction on microbiota-host crosstalk and of the first two symposia: new approaches in microbiota characterization, and gut inflammation.
Introductory lecture – Microbiota-host crosstalks: Decrypting signals in the crypt
Prof. Philippe Sansonetti, Institut Pasteur, Paris, France
After introducing the concept of the gut microbiota-host symbiosis, Prof. Sansonetti talked about the crypt-specific gut microbiota. The presence of stem cells and paneth cells in the crypts, which are important cells for intestinal homeostasis, make this particular niche very interesting to study. Prof. Sansonetti explained that the crypt specific core microbiota is composed of aerobic and non-fermentative species. He focused his talk on the role of crypt microbiota in differentiation and maturation of the crypts and on the mechanisms involved in these gut microbiota-host interactions using the organoid model. Different gut microbiota components (peptidoglycan, muramyl-dipeptide) are involved in these cytoprotective effects.
Symposium 1 – New approaches in microbiota characterization
Prof. Joël Doré, INRA-Micalis, Jouy-en-Josas, France – Metagenome: Man-gut microbiota symbiosis disruption diseases
Prof. Doré talked about the principal characteristics of the gut metagenome and current approaches for analyzing metagenomic data. He spoke about “The International Human Microbiome Standards” (IHMS) project, which aims to coordinate the development of standard operating procedures to optimize data quality and comparability in the human microbiome field. He also presented the concept of using co-abundant genes across a series of metagenomic samples to make possible the assembly of microbial genomes without the need for reference sequences.
Prof. Doré also presented different studies showing the potential usefulness of gut microbiota analysis for risk detecting the risk of a disease, diagnosing a disease, or patient monitoring of diseases such as liver cirrhosis and obesity. Gene richness appears to be of particular interest in that context.
Prof. Gary Wu, University of Pennsylvania School of Medicine, Philadelphia, USA – Diet, the gut microbiome and its metabolome in health and diseases
Prof. Wu explained how the host may interact with the gut microbiota through mucin and antimicrobial peptide production as well as how the microbiota may interact with us through their metabolites such as short chain fatty acids for instance. Other factors may also influence these interactions: diet, antibiotics and xenobiotics with their capability to shape the gut microbiota.
Diet not only shapes gut microbiota composition but also metabolites produced by the gut microbiota (such as trimethylamine-N-oxide or TMAO) which may impact on diseases (cardiovascular disease for TMAO). The gut microbiome and metabolome determine the relation between dietary consumption and the metabolite products that are ultimately present in the gut lumen and plasma of the human and affect the host. To illustrate this concept, Prof. Wu analyzed gut microbiota composition and plasma metabolome in healthy human vegans or omnivores living in an urban USA environment. Plasma metabolome of vegans differs markedly from omnivores whereas gut microbiota composition was more similar. Importantly, the gut microbiota influenced metabolite production from dietary substrates. This highlights the importance of considering the composition of the gut microbiota when developing prebiotics as substrate to produce desirable metabolites with beneficial effects.
Symposium 2 – Gut inflammation: from physiology to pathology
Prof. Arthur Kaser, University of Cambridge, UK – Impaired autophagy, endoplasmic reticulum stress and Crohn’s disease
Prof. Kaser talked about the genetic variant for ATG16L1 (involved in autophagy pathway actions) which is one of the three strongest genetic risk factors of Crohn’s disease. Autophagy dysfunction due to this genetic defect causes endoplasmic reticulum (ER) stress in Paneth cells which is a common feature in inflammatory bowel diseases. Moreover, using a mouse model for ER stress in intestinal epithelial cells (IEC XBP1 deleted mice), he showed that ER stress in genetically deficient mice for ATG16L1 results in Crohn’s-disease-like ileitis. Importantly, Prof. Kaser proposed a role of ileitis-associated gut microbiota dysbiosis in the disease.
Prof. Nicolas Barnich, University of Clermont-Ferrand, France – Bacteria and inflammation
Prof. Barnich discussed gut microbiota changes associated with inflammatory bowel diseases and in particular the emergence of opportunistic pathogens (adherent-invasive Escherichia coli) and the decrease in Faecalibacterium praustnitzii during Crohn’s disease. The gut mucosal colonization with adherent-invasive Escherichia coli (AIEC) may drive the disease through triggering intestinal inflammation. He discussed a role for the abnormal expression of CEACAM6 (carcinoembryonic antigen-related cell adhesion molecule 6) during Crohn’s disease since AIEC are able to interact with CEACAM6 and to induce expression of this receptor. However, human CEACAM6 expression alone is not sufficient to provoke adherent-invasive Escherichia coli colonization in mice. He talked about the impact of the Western diet in that context since high-fat diet consumption constitutes a risk for inflammatory bowel diseases. He showed that only in the context of a Western diet does CAECAM6 expression lead to a higher ability of AIEC bacteria to colonize the gut mucosa and to induce inflammation. The second part of his talk was dedicated to epigenetic modulations of CEACAM6 gene by microorganisms and environmental factors. He also discussed the development of therapy using mannosides and Saccharomyces cerevisiae for AIEC eradication.
Prof. Jonathan M Rhodes, University of Liverpool, UK – Microbiota-diet interactions in inflammatory bowel diseases and colon cancer
Prof. Rhodes talked about changes in the mucosa-associated microbiota, including the increase in Escherichia coli, during inflammatory bowel diseases and colon cancer. Accordingly, he proposed that dietary components capable of blocking bacteria-epithelial adherence could have beneficial effects in these diseases. Among these dietary components he discussed the effects of soluble dietary fibers which are able to block Escherichia coli adhesion and invasion in colon epithelial cells and to inhibit translocation to Peyer’s patches. Interestingly the effects of dietary fibers on bacterial adhesion are mediated by interactions with the epithelium and not by interactions with the bacteria themselves. Importantly, other dietary components such as emulsifiers and detergents may be harmful by increasing bacterial translocation. He showed a correlation between emulsifier intake and incidence of Crohn’s disease, suggesting that the increase in consumption of emulsifiers in processed food during these last few decades could be an explanation for the rising incidence of Crohn’s disease.
Prof. Dirk Haller, University of Munich, Germany – Microbiota modulation in inflammatory bowel diseases
After discussing gut microbiota dysbiosis and the reduction in microbial gene richness associated with inflammatory bowel diseases, Prof. Haller addressed the following question: is this dysbiosis in the bacterial community causally linked to adverse effects in the host such as the onset of ileitis? By using a model of spontaneous ileitis in germ-free mice he showed that the disease is microbiota-dependent, since no ileitis is observed in germ-free mice whereas mice in a conventional animal facility develop intestinal inflammation. Moreover, dysbiotic microbiota transplantation to germ-free mice induces Crohn’s disease-like inflammation in genetically susceptible recipients. He also showed that in specific-pathogen-free conditions, not all the mice will develop Crohn’s disease-like ileitis; some of them are non-responders. Interestingly, gut microbiota from non-responder mice clustered with wild type mice, whereas gut microbiota from responder mice clustered separately. Gut colonization of germ-free mice with non-responder gut microbiota did not result in colitis. During his presentation, Prof. Haller showed the causal relationship between intestinal dysbiosis and inflammatory bowel diseases.