Plasticity of gastro-intestinal mucosa in nutritional pathologies and after surgery (PIMS)
Team Le Gall / Bado
Department Hepato-Gastroenterology Department
Our team focus on the contribution of the gastrointestinal tract to nutritional pathologies including obesity, which is often associated with comorbidities such as type 2 diabetes or non-alcoholic fatty liver disease (NAFLD). The pharmacotherapy of obesity remains inconstant and today bariatric surgeries that are remodeling of the gastrointestinal tract are the only effective treatments when obesity becomes morbid. While these surgeries are generally extremely beneficial, we have reported that they can lead to intestinal failure, with severe malnutrition, microvesicular steatosis, and acute liver failure (Lancet. 2013). These clinical observations are reminiscent of the short bowel syndrome (SBS) resulting from an extensive resection of the small intestine and responsible for the main cause of intestinal failure.
Managing these pathologies – obesity and malnutrition resulting from intestinal failure – with increasing human, social and economic costs, requires research efforts to better understand their origins and identify new targets and therapeutic strategies.
To meet these social needs, our team gathers physiologists of the gastro-intestinal tract, basic scientists and clinicians (digestive surgeons, gastroenterologists and nutritionists) to develop basic and transitional researches to study gastrointestinal adaptations in response to obesity, surgical remodeling, and nutritional status (undernutrition / malnutrition).
We set up unique rat models of bariatric surgeries as vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB) and one-anastomosed gastric bypass (OAGB) (PLoS One 2015, Am J Physiol 2016, J Vis Exp. 2018) and rat models of Short Bowel Syndrome (jejuno-colonic or jejunum-ileum anastomosis) (Sci. Rep. 2016).
Combining experimental research in these preclinical models with clinical studies, we identified differences in intestinal adaptation that contribute to improved glucose homeostasis after RYGB vs VSG-type bariatric surgeries (Gastroenterology 2016; Trends Endocrinol Metab. 2017). We also characterized the structural and functional adaptations of residual intestinal mucosa and microbiota in humans and rats with short bowel syndrome (Sci. Rep. 2016, Microorganisms 2016, Front. Physiol. 2017).
In all these studies, we highlighted the plasticity of the gastrointestinal tract epithelial cells and its consequences on intestinal functions (Nutr Rev. 2018).
We are now extending our studies to both side of the intestinal epithelium: the mucosa layers containing the enteric nervous system (ENS) and immune cells versus the luminal microbiota. Our goal is to determine the functional consequences of changes in enteric neuronal and immune cells and microbiota on intestinal epithelial cell function.
Finally, “omics” studies of the intestinal mucosa in preclinical models and in patients will allow to identify new biomarkers and therapeutic targets to complement or replace surgery
Gastrointestinal tract anatomy in physiology and after remodeling by surgery.
A. Normal gastrointestinal tract anatomy.
B. Gastrointestinal tract anatomy after bariatric surgerie as vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB), or one-anastomosis gastric bypass (OAGB).
B. Gastrointestinal tract anatomy after massive resection of the intestine leading to short bowel syndrome (SBS). Three categories are recognized: end-jejunostomy with no colon and ileum (type 1); jejuno-colic anastomosis with no ileum and no ileocecal valve (type 2); and jejuno-ileal anastomosis preserving colon, ileo-cecal valve, and distal part of the ileum (type 3). Adapted from Nutr Rev. 2018.
Intestinal reprogramming and improvement of glucose homeostasis after bariatric surgery.
After RYGB, the jejunal mucosa in the alimentary limb becomes hyperplasic in rats, as well as in RYGB-operated obese subjects (compared to obese subjects). This hyperplasia is associated with a metabolic hyperactivity of the alimentary limb and results in increased glucose consumption, which can be visualized by PET / CT Scan analyses in humans. Adapted from Gastroenterology 2016
The gut connectome
Both sides of the gastro-intestinal epithelium could contribute to the adaptations in response to surgery readouts. In the mucosa, glial and neurons of the enteric nervous system and immune cells directly communicate with epithelial cells. In the outer side, microbiota-produced metabolites feed or signal intestinal epithelial cells
Translational research within the PIMS team
Our team gathers physiologists of the gastro-intestinal tract, basic scientists and clinicians (digestive surgeons, gastroenterologists and nutritionists) to develop bench-to-bedsides as well as bedside-to-bench researches.
Publication date : 04 January 2021 More
Bariatric surgery induces a new gastric mucosa phenotype with increased functional glucagon-like peptide-1 expressing cells Nature Communications
Autors : Ribeiro-Parenti Lara Anne-Charlotte Jarry Jean-Baptiste Cavin Willemetz Alexandra Le Beyec Le Bihan Johanne Aurélie Sannier Benadda Samira Pelletier Anne-Laure Muriel Hourseau Thibaut Léger Bastien Morlet Couvelard Anne Younes Anini Msika Simon Marmuse Jean-Pierre Ledoux Séverine Le Gall Maude Bado André
Publication date : 27 October 2020 More
Endocannabinoid Receptor-1 and Sympathetic Nervous System Mediate the Beneficial Metabolic Effects of Gastric Bypass Cell Rep.
Autors : Yuanchao Ye Marwa Abu El Haija Donald A Morgan Deng Guo Yang Song Aaron Frank Liping Tian Ruth A Riedl Colin M L Burnett Zhan Gao Zhiyong Zhu Shailesh K Shahi Kasra Zarei Couvelard Anne Poté Nicolas Ribeiro-Parenti Lara Bado André Lama Noureddine Andrew Bellizzi Paul Kievit Ashutosh K Mangalam Leonid V Zingman Le Gall Maude Justin L Grobe Lee M Kaplan Deborah Clegg Kamal Rahmouni Mohamad Mokadem
Publication date : 06 July 2020 More
Short Bowel Syndrome: A Paradigm for Intestinal Adaptation to Nutrition? Annu Rev Nutr.
Autors : Le Beyec Le Bihan Johanne Billiauws Lore Bado André Joly Francisca Le Gall Maude
Publication date : 30 April 2020 More
Long-term consequences of one anastomosis gastric bypass on esogastric mucosa in a preclinical rat model Scientific Reports
Autors : Matthieu Siebert Ribeiro-Parenti Lara Nicholas D. Nguyen Muriel Hourseau Belinda Duchêne Lydie Humbert Nicolas Jonckheere Grégory Nuel Jean-Marc Chevallier Henri Duboc Dominique Rainteau Simon Msika Nathalie Kapel Anne Couvelard Bado André Le Gall Maude
Publication date : 16 October 2019 More
Effect of different bariatric surgeries on dietary protein bioavailability in rats Physiol Gastrointest Liver Physiol
Autors : Tessier R Ribeiro-Parenti Lara Bruneau O Khodorova N Cavin JB Bado André Azzout-Marniche D Calvez J Le Gall Maude Gaudichon C
Publication date : 01 April 2019 More
Neuromedin U is a gut peptide that alters oral glucose tolerance by delaying gastric emptying via direct contraction of the pylorus and vagal-dependent mechanisms. FASEB J. 2019 Apr;33(4):5377-5388
Autors : Jarry AC Merah N Cisse Fanta Cayetanot F Fiamma MN Willemetz Alexandra Gueddouri D Barka B Valet P Guilmeau S Bado André Le Beyec Le Bihan Johanne Bodineau L Le Gall Maude
Publication date : 01 March 2019 More
Intestinal plasticity in response to nutrition and gastrointestinal surgery. Nutr Rev
Autors : Le Gall Maude Thenet S Aguanno D Jarry AC1 Genser L Ribeiro-Parenti Lara Joly Francisca Ledoux Séverine Bado André Le Beyec Le Bihan Johanne
Publication date : 15 February 2019 More
Gastric bypass specifically impairs liver parameters as compared with sleeve gastrectomy, independently of evolution of metabolic disorders. Surg Obes Relat Dis
Autors : Ledoux Séverine Sami O Calabrese D Le Gall Maude Flamant Martin Coupaye Muriel
Publication date : 01 February 2019 More
Roux-en-Y Gastric-Bypass and sleeve gastrectomy induces specific shifts of the gut microbiota without altering the metabolism of bile acids in the intestinal lumen Int J Obes (Lond). 2019 Feb;43(2):428-431.
Autors : Duboc Henri Nguyen CC Cavin JB Ribeiro-Parenti Lara Jarry AC Rainteau D Humbert L Coffin B Le Gall Maude Bado André Sokol H
Publication date : 19 April 2017 More
Microbiota Is Involved in Post-resection Adaptation in Humans with Short Bowel Syndrome. Front Physiol. 2017 Apr 19;8:224. doi: 10.3389/fphys.2017.00224. eCollection 2017
Autors : Gillard L Mayeur C Robert V Pingenot I Le Beyec Le Bihan Johanne Bado André Lepage P Thomas M Joly Francisca
Publication date : 21 June 2016 More
Enhanced Ghrelin Levels and Hypothalamic Orexigenic AgRP and NPY Neuropeptide Expression in Models of Jejuno-Colonic Short Bowel Syndrome. Sci Rep.
Autors : Gillard L Billiauws Lore Stan-Iuga B Ribeiro-Parenti Lara Jarry AC Cavin JB Cluzeaud F Mayeur C Thomas M Freund JN Lacorte JM Le Gall Maude Bado André Joly Francisca Le Beyec Le Bihan Johanne
Publication date : 15 February 2016 More
Differences in Alimentary Glucose Absorption and Intestinal Disposal of Blood Glucose After Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy Gastroenterology. 2016 Feb;150(2):454-64
Autors : Cavin JB Couvelard Anne Lebtahi Rachida Ducroc R Arapis K Voitellier E Cluzeaud F Gillard L Hourseau M Mikail N Ribeiro-Parenti Lara Kapel N Marmuse Jean-Pierre Bado André Le Gall Maude