|
|
|
EQUIPE 3 : PHYSIOPATHOLOGIE DE L'AXE INTESTIN-CERVEAU
TEAM 3 : PHYSIOPATHOLOGY OF GUT BRAIN AXIS |
Mini CV
Since 2021 : Research Director 2 , Physiopathology Of Gut Brain Axis, Digestive health research institute, INSERM U1220, Toulouse, France
Since 2016: Research scientist, research team intestinal neuroimmune interaction, Digestive health research institute, INSERM U1220, Toulouse, France 2011-2015: Research scientist, research team on Mediators of inflammation and pain directed, Dept. of Immunology and Infectious Diseases, INSERM U1043, Toulouse, France. 2007-2011: Post-doctoral fellow, Dept of Immunology and Infectious Diseases, INSERM U563, Toulouse, France. 2004-2007: Post-doctoral fellow, Dept of Pharmacology and Therapeutics, University of Calgary Canada. 2001-2004: PhD Student, University of Toulouse, France, Dept of Neuro-Gastroenterology & Nutrition, INRA Toulouse, France.
|
expertise
|
Recherche/projet research/project
Role of bacterial and host lipids in intestinal homeostasis
Irritable bowel syndrome (IBS) is characterized by abdominal pain and bowel dysfunction such as constipation (IBSC), diarrhea (IBS-D), or mixed bowel patterns. It affects about 5% of the French population and 11% worldwide; it is the most frequent functional intestinal disorder in patients visiting general practitioners or gastroenterologists. While IBS is not a life-threatening disease, it can be responsible for an important alteration of quality of life (QoL) affecting all its dimensions. This alteration of QoL is superior to that observed in other chronic diseases such as diabetes or Crohn’s disease. The absence of knowledge about etiology, the extent of the symptoms and the poor efficiency of therapeutics available make IBS extremely difficult to treat. The pathophysiology of IBS is multifactorial and still poorly understood. Translational research using patient biopsies highlighted a pronociceptive environment in IBS characterized by an increase in pro-inflammatory nociceptive mediators activating sensory neurons and inducing pain5. Our team has demonstrated that several bioactive lipids (5,6-EET, 5-oxoETE or PGE2) are increased in gut biopsies of IBS patients and have nociceptive properties6,7. These studies have shown that bioactive lipids could directly stimulate sensory nerves via the activation of nociceptors and induce visceral hypersensitivity. IBS is now rather described as the result of an alteration in bidirectional interactions between the colon and the enteric and central nervous system. The description of a dysbiosis in IBS has added a new dimension to this paradigm. Transfer of the gut microbiota from IBS patients, but not from healthy individuals, induces intestinal dysfunction, such as visceral hypersensitivity, in axenic rats similar to that seen in IBS patients suggesting that the gut microbiota contributes to the symptoms associated with IBS. Multiple reports have linked IBS pathogenesis with gut microbiota dysbiosis, a condition that refers to decrease/loss of microbial diversity and richness, owing to the changes from commensal bacteria to pathogens in the human gut. Nevertheless, there is a discrepancy in the bacterial composition reported by the different studies. For instance, in IBS-D, Tap and colleagues quantified an increase in Bacteroides and in contrast, Su and collaborators described a decrease in the same IBS subtype. A functional microbiota is formed by the repertoire of expressed genes and, even more importantly, by proteins and metabolites. In IBS, a lot of studies investigated the compositional level but few studies have investigated active genes, proteins, or metabolites. However, studies of molecules produced by the microbiota may be more relevant than composition when it comes to understand the role played by microbiota in host function. In fact, the taxonomic composition of the human microbiome varies tremendously across individuals, while its functional capacity is highly conserved across individuals. This conserved functional capacity is defined as the functional redundancy of the microbiota. Although this redundancy is important to maintain the stability and resilience of the human microbiome, it introduces the idea that species are may be substituable in a given microbiota in terms of function. Unlike inflammatory bowel disease, no increase in bacterial translocation could be observed in IBS patients indicating that if the bacteria have an impact on visceral pain, this is done through the action of the molecules, secreted and/or transformed by the bacteria, able to cross the intestinal barrier. Amongst metabolites, several bacterial lipids including lipopeptides, long chain and short chain fatty acid or secondary bile acids have been described for their capacity to cross the epithelial barrier. Our general aim is to identify lipid metabolites differentially produced by the gut microbiota of IBS patients and to determine their effect on the host with a focus on intestinal homeostasis.
Irritable bowel syndrome (IBS) is characterized by abdominal pain and bowel dysfunction such as constipation (IBSC), diarrhea (IBS-D), or mixed bowel patterns. It affects about 5% of the French population and 11% worldwide; it is the most frequent functional intestinal disorder in patients visiting general practitioners or gastroenterologists. While IBS is not a life-threatening disease, it can be responsible for an important alteration of quality of life (QoL) affecting all its dimensions. This alteration of QoL is superior to that observed in other chronic diseases such as diabetes or Crohn’s disease. The absence of knowledge about etiology, the extent of the symptoms and the poor efficiency of therapeutics available make IBS extremely difficult to treat. The pathophysiology of IBS is multifactorial and still poorly understood. Translational research using patient biopsies highlighted a pronociceptive environment in IBS characterized by an increase in pro-inflammatory nociceptive mediators activating sensory neurons and inducing pain5. Our team has demonstrated that several bioactive lipids (5,6-EET, 5-oxoETE or PGE2) are increased in gut biopsies of IBS patients and have nociceptive properties6,7. These studies have shown that bioactive lipids could directly stimulate sensory nerves via the activation of nociceptors and induce visceral hypersensitivity. IBS is now rather described as the result of an alteration in bidirectional interactions between the colon and the enteric and central nervous system. The description of a dysbiosis in IBS has added a new dimension to this paradigm. Transfer of the gut microbiota from IBS patients, but not from healthy individuals, induces intestinal dysfunction, such as visceral hypersensitivity, in axenic rats similar to that seen in IBS patients suggesting that the gut microbiota contributes to the symptoms associated with IBS. Multiple reports have linked IBS pathogenesis with gut microbiota dysbiosis, a condition that refers to decrease/loss of microbial diversity and richness, owing to the changes from commensal bacteria to pathogens in the human gut. Nevertheless, there is a discrepancy in the bacterial composition reported by the different studies. For instance, in IBS-D, Tap and colleagues quantified an increase in Bacteroides and in contrast, Su and collaborators described a decrease in the same IBS subtype. A functional microbiota is formed by the repertoire of expressed genes and, even more importantly, by proteins and metabolites. In IBS, a lot of studies investigated the compositional level but few studies have investigated active genes, proteins, or metabolites. However, studies of molecules produced by the microbiota may be more relevant than composition when it comes to understand the role played by microbiota in host function. In fact, the taxonomic composition of the human microbiome varies tremendously across individuals, while its functional capacity is highly conserved across individuals. This conserved functional capacity is defined as the functional redundancy of the microbiota. Although this redundancy is important to maintain the stability and resilience of the human microbiome, it introduces the idea that species are may be substituable in a given microbiota in terms of function. Unlike inflammatory bowel disease, no increase in bacterial translocation could be observed in IBS patients indicating that if the bacteria have an impact on visceral pain, this is done through the action of the molecules, secreted and/or transformed by the bacteria, able to cross the intestinal barrier. Amongst metabolites, several bacterial lipids including lipopeptides, long chain and short chain fatty acid or secondary bile acids have been described for their capacity to cross the epithelial barrier. Our general aim is to identify lipid metabolites differentially produced by the gut microbiota of IBS patients and to determine their effect on the host with a focus on intestinal homeostasis.
