Group discussion around Pawel Kiela (Arizona): Two recent papers on dysbiosis and Intestinal Na+/H+ Exchange

Dr. Pawel KIELA
Department of Pediatrics- Steele Children’s Research Center- University of Arizona Health Sciences Center – TUCSON – AZ – USA
Two papers of his will be discussed during this group discussion:

Reduced Epithelial Na+/H+ Exchange Drives Gut Microbial Dysbiosis and Promotes Inflammatory Response in T Cell-Mediated Murine Colitis

Microbial Dysbiosis Associated with Impaired Intestinal Na+/H+ Exchange Accelerates and Exacerbates Colitis in Ex-Germ Free Mice



Pawel Kiela (Arizona), Connection between epithelial Na+/H+ exchange, gut microbiome, inflammation, colon cancer

Dr. Pawel KIELA
Department of Pediatrics- Steele Children’s Research Center- University of Arizona Health Sciences Center – TUCSON – AZ – USA


Les conférences FR TransBioMed
Invitation : Claire Larmonier – David Laharie – Thomas Pradeu – ImmunoConcEpT


The delicate connection between epithelial Na+/H+ exchange, gut microbiome, inflammation, and colon cancer

Pathogenic microorganisms as well as inflammatory mediators associated with acute infections or with chronic inflammatory bowel diseases (IBD) lead to inhibition of epithelial Na+/H+ exchange, a phenomenon commonly interpreted as leading to infection/inflammation- associated diarrhea. Moreover, chronic NHE3 deficiency exacerbates inflammation in part by promoting microbial dysbiosis. Our recent work indicates, however, that the effects of NHE3 inhibition are much more complex and may not be unidirectional in promoting pathology. Biology offers a plethora of examples of “double-edged swords”, whereby the same process, molecule or its regulation, plays protective or detrimental roles depending on the context, source, or the extent/duration of response. Short term inhibition of NHE3 may represent an evolutionarily permissible process in certain cases (infection or epithelial restitution), while in more chronic diseases like IBD or colorectal cancer, decreased or eliminated NHE3 activity leads to changes in gut microbiota and epithelial cell metabolism that furthers the disease process. These studies change the way we view Na+/H+ exchange in the context of infection/inflammation and colorectal cancer progression and shed new light into the novel roles of NHE3 in mucosal homeostasis and disease progression.

Raphael Enaud (Bordeaux University Hospital), Microbiota and cystic fibrosis: a new era?

Raphael Enaud (MD-PhD student) & Laurence Delhaes (MD-PhD)
Cystic fibrosis (CF) is the most common serious genetic disease in Caucasian population. Patient management has improved considerably in recent years. Pulmonary transplantation and protein therapeutics have changed the face of the disease. Before the first lung transplant, the CF disease prognosis was essentially conditioned by the respiratory function deterioration. Since then, the life expectancy of patients has increased and a new reality is emerging: cystic fibrosis is a systemic disease and affects other organs, notably the intestine, which is the site of chronic inflammation. New physiopathological, diagnostic and therapeutic issues emerge.
The research in cystic fibrosis domain did not escape the advent of microbiota analysis using metagenomics, and give us the opportunity to share with you current knowledges on CF microbiota. How does it constitute a new era in CF management? In which way can it explain the intestinal inflammation? Does the gut-lung axis represent a major pathway? Can gut microbiota be used as diagnostic or therapeutic tools?

Silvia Bulgheresi (University of Vienna), Dressed to Cooperate – Marine Nematode-Bacterium Symbioses

Silvia Bulgheresi (University of Vienna, Austria, Department of Ecogenomics & Systems Biology)

Up to now, the study of bacterial reproduction focused on model organisms. On the other hand, cell biological research on environmental bacteria – including those thriving on animal surfaces – are scarce. Marine nematodes engage in binary associations with chemosynthetic Gammaproteobacteria. The spatial dispositions of the bacterial symbionts on the surface of their cognate hosts is species-specific, invariable, and mediated by extraordinary reproductive strategies: the rod-shaped Laxus oneistus and Robbea hypermnestra symbionts widen and set their septation planes longitudinally (Leisch et al., 2012, 2016). The Eubostrichus fertilis symbiont can divide at virtually every length between 4 and 45 µm resulting in an unprecedented 10-fold length variation within the same cell population. Finally, the up to 120 µm-long E. dianeae symbiont is the longest bacteria known to divide by symmetric transverse fission (Pende et al., 2014). We want to determine the molecular and cellular mechanisms underlying the anomalous reproductive strategies of animal-attached bacteria and their ecological significance.

Thomas Bosch (Kiel), The Holobiont Imperative: Novel Perspectives for Biology and Medicine

Thomas Bosch (Zoologisches Institut, University of Kiel, Germany; Head of DFG project “Origin and Function of Metaorganisms”)

For a long time, the main purpose of host-associated microbiology was to study pathogenic bacteria and infectious disease; the potential benefit of good bacteria remained unrecognized. In the last 10 years, biology has made revolutionary advances from century-old debates about the relative importance of non-pathogenic bacteria. Today we know that individuals are not solitary, homogenous entities but consist of complex communities of many species that likely evolved during a billion years of coexistence. Holobionts (hosts and their microbes) and hologenomes (all genomes of the holobiont) are multipartite entities that result from ecological, evolutionary and genetic processes. I propose, therefore, that the health of animals, including humans, is fundamental multi-organismal; that any disturbance within the complex community of host and microbial cells has drastic consequences for the wellbeing of the individual member of this association; and that the microbiome can be viewed as an organ of the host. This newfound awareness of the dependency of phenotypes on other species and environmental conditions presents additional layers of complexity for evolutionary theory and raises many questions that are being addressed by new research programmes.

CANCELLED: Charlotte Brives (Centre Emile Durkheim, Bordeaux), The promises of phage therapy

This event is cancelled.
Charlotte Brives (Centre Emile Durkheim, Sciences Po Bordeaux, France)
The promises of phage therapy, or why phages are such an interesting object for anthropologists.
Phage therapy, the use of bacteriophage viruses to treat human bacterial infections, is a century-old practice developed in 1917 by Félix d’Hérelle. After an expansion phase, however, its use declined in Western Europe and the United States from the 1930s onwards. For several years, faced with the emergence of bacterial multi- or even toti-resistant to antibiotics, there has been a desire on the part of various players to see this therapy develop again. The decline and re-emergence of a very particular therapy that makes use of dynamic biological entities is a particularly interesting phenomenon for anthropology. This presentation will be an opportunity to present certain elements on the way biomedical knowledge is produced and used and to better question their underlying representations and conceptions (of the world, health, disease, relationships to other species). We will also see how these concepts, far from being neutral, cut across fields as diverse as science, law, or economics, and how they impose on public health practices and choices.
Charlotte Brives (chargée de recherche, CNRS) is specialized in anthropology of science and anthropology of medicine.

Murielle Thomas (INRA Jouy), The contribution of the microbiota to gut and lung physiology

Muriel Thomas (Micalis, INRA Jouy-en-Josas, PI “Epithelium and microbiota” team, France)

Full PDF presentation: Thomas Muriel_Bordeaux talk
The microbiota inhabiting the gut is a main actor of digestive physio-pathology, and we have contributed to show that the bacterial colonization is critical for a proper homeostasis of intestinal epithelial cells (1-5). Our data show how microbiota, specifically the primo-colonizing bacteria arriving early after birth, may impact genuine features of epithelium by considering its morphology, secretive, absorptive and storage functions. After decades of research about gut microbiota, it is well established that bacterial families strongly impact gut immunity and physiology in a specific manner.
In 2010, the lung microbiota has been described, disturbing the ancient dogma based on the absence of microbes in healthy lungs. The lung bacterial community involves mainly Pseudomonas, Streptococcus, Prevotella, Fusobacteria, and Veillonella in healthy human lungs and the bacterial load and composition are changing along respiratory pathologies. Thus, based on our expertise in gut, we have recently developed a new area of research in our team to study the impact of lung microbiota on lung physiology. In this context, we focused our study on the effect of lung microbiota in the susceptibility to asthma (model using the sensitization and a challenge with House Dust Mite). We have established that a microbial education of the mucosal microenvironment occurs in the lung and that appropriate bacterial lung stimuli during early life are critical for allergic asthma susceptibility. Our study brings evidence that there is a reciprocal influence between lung bacteria and asthma in neonatal mice, highlighting the bacterial impact on respiratory pathophysiology.
1.              Rul, F., Ben-Yahia, L., Chegdani, F., Wrzosek, L., Thomas, S., Noordine, M. L., Gitton, C., Cherbuy, C., Langella, P., and Thomas, M. (2011) Impact of the metabolic activity of Streptococcus thermophilus on the colon epithelium of gnotobiotic rats. J Biol Chem 286, 10288-10296
2.              Wrzosek, L., Miquel, S., Noordine, M. L., Bouet, S., Joncquel Chevalier-Curt, M., Robert, V., Philippe, C., Bridonneau, C., Cherbuy, C., Robbe-Masselot, C., Langella, P., and Thomas, M. (2013) Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii influence the production of mucus glycans and the development of goblet cells in the colonic epithelium of a gnotobiotic model rodent. BMC Biol 11, 61
3.              Deschemin, J. C., Noordine, M. L., Remot, A., Willemetz, A., Afif, C., Canonne-Hergaux, F., Langella, P., Karim, Z., Vaulont, S., Nicolas, G and Thomas, M. (2016) The microbiota shifts the iron sensing of intestinal cells. FASEB J. Jan;30(1):252-61.
4.              Miquel, S., Leclerc, M., Martin, R., Chain, F., Lenoir, M., Raguideau, S., Hudault, S., Bridonneau, C., Northen, T., Bowen, B., Bermudez-Humaran, L. G., Sokol, H., Thomas, M., and Langella, P. (2015) Identification of metabolic signatures linked to anti-inflammatory effects of Faecalibacterium prausnitzii. MBio 6
5.              Tomas, J., Reygner, J., Mayeur, C., Ducroc, R., Bouet, S., Bridonneau, C., Cavin, J. B., Thomas, M., Langella, P., and Cherbuy, C. (2015) Early colonizing Escherichia coli elicits remodeling of rat colonic epithelium shifting toward a new homeostatic state. ISME J 9, 46-58