TY - JOUR
T1 - Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism
AU - Zhang, Xufei
AU - Grosfeld, Alexandra
AU - Williams, Edek
AU - Vasiliauskas, Daniel
AU - Barretto, Sharon
AU - Smith, Lorraine
AU - Mariadassou, Mahendra
AU - Philippe, Catherine
AU - Devime, Fabienne
AU - Melchior, Chloé
AU - Gourcerol, Guillaume
AU - Dourmap, Nathalie
AU - Lapaque, Nicolas
AU - Larraufie, Pierre
AU - Blottière, Hervé M.
AU - Herberden, Christine
AU - Gerard, Philippe
AU - Rehfeld, Jens F.
AU - Ferraris, Ronaldo P.
AU - Fritton, J. Christopher
AU - Ellero-Simatos, Sandrine
AU - Douard, Veronique
N1 - Funding Information:
The authors thank J. P. Furet (Micalis Institute, INRA, Jouyen-Josas, France), F. Rouyer (Paris-Saclay Institute of Neuroscience, Université Paris Sud, CNRS, Université Paris–Saclay, Gif-sur-Yvette, France), and S. P. Shirazi-Beechey (Institute of Integrative Biology, University of Liverpool, United Kingdom) for sharing reagents and equipment. The authors are grateful to the INRA Migale bioinformatics platform (http://migale.jouy.inra.fr/) for providing computational resources, the Genotoul high-throughput sequencing platform (http://bioinfo.genotoul.fr/), and the histology facility of UMR 1313 Génétique Animale et Biologie Integrative (GABI). This work was supported by grants from Institut Benjamin Delessert and by INRA. The China Scholarship Council (CSC) and INRA funded PhD fellowships to X.Z. The authors declare no conflicts of interest.
Publisher Copyright:
© FASEB
PY - 2019/6/1
Y1 - 2019/6/1
N2 - Current fructose consumption levels often overwhelm the intestinal capacity to absorb fructose. We investigated the impact of fructose malabsorption on intestinal endocrine function and addressed the role of the microbiota in this process. To answer this question, a mouse model of moderate fructose malabsorption [ketohexokinase mutant (KHK)−/−] and wild-type (WT) littermate mice were used and received a 20%-fructose (KHK-F and WT-F) or 20%-glucose diet. Cholecystokinin (Cck) mRNA and protein expression in the ileum and cecum, as well as preproglucagon (Gcg) and neurotensin (Nts) mRNA expression in the cecum, increased in KHK-F mice. In KHK-F mice, triple-label immunohistochemistry showed major up-regulation of CCK in enteroendocrine cells (EECs) that were glucagon-like peptide-1 (GLP-1)+/Peptide YY (PYY−) in the ileum and colon and GLP-1−/PYY− in the cecum. The cecal microbiota composition was drastically modified in the KHK-F in association with an increase in glucose, propionate, succinate, and lactate concentrations. Antibiotic treatment abolished fructose malabsorption-dependent induction of cecal Cck mRNA expression and, in mouse GLUTag and human NCI-H716 cells, Cck mRNA expression levels increased in response to propionate, both suggesting a microbiota-dependent process. Fructose reaching the lower intestine can modify the composition and metabolism of the microbiota, thereby stimulating the production of CCK from the EECs possibly in response to propionate.—Zhang, X., Grosfeld, A., Williams, E., Vasiliauskas, D., Barretto, S., Smith, L., Mariadassou, M., Philippe, C., Devime, F., Melchior, C., Gourcerol, G., Dourmap, N., Lapaque, N., Larraufie, P., Blottière, H. M., Herberden, C., Gerard, P., Rehfeld, J. F., Ferraris, R. P., Fritton, J. C., Ellero-Simatos, S., Douard, V. Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism. FASEB J. 33, 7126–7142 (2019). www.fasebj.org.
AB - Current fructose consumption levels often overwhelm the intestinal capacity to absorb fructose. We investigated the impact of fructose malabsorption on intestinal endocrine function and addressed the role of the microbiota in this process. To answer this question, a mouse model of moderate fructose malabsorption [ketohexokinase mutant (KHK)−/−] and wild-type (WT) littermate mice were used and received a 20%-fructose (KHK-F and WT-F) or 20%-glucose diet. Cholecystokinin (Cck) mRNA and protein expression in the ileum and cecum, as well as preproglucagon (Gcg) and neurotensin (Nts) mRNA expression in the cecum, increased in KHK-F mice. In KHK-F mice, triple-label immunohistochemistry showed major up-regulation of CCK in enteroendocrine cells (EECs) that were glucagon-like peptide-1 (GLP-1)+/Peptide YY (PYY−) in the ileum and colon and GLP-1−/PYY− in the cecum. The cecal microbiota composition was drastically modified in the KHK-F in association with an increase in glucose, propionate, succinate, and lactate concentrations. Antibiotic treatment abolished fructose malabsorption-dependent induction of cecal Cck mRNA expression and, in mouse GLUTag and human NCI-H716 cells, Cck mRNA expression levels increased in response to propionate, both suggesting a microbiota-dependent process. Fructose reaching the lower intestine can modify the composition and metabolism of the microbiota, thereby stimulating the production of CCK from the EECs possibly in response to propionate.—Zhang, X., Grosfeld, A., Williams, E., Vasiliauskas, D., Barretto, S., Smith, L., Mariadassou, M., Philippe, C., Devime, F., Melchior, C., Gourcerol, G., Dourmap, N., Lapaque, N., Larraufie, P., Blottière, H. M., Herberden, C., Gerard, P., Rehfeld, J. F., Ferraris, R. P., Fritton, J. C., Ellero-Simatos, S., Douard, V. Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism. FASEB J. 33, 7126–7142 (2019). www.fasebj.org.
KW - CCK
KW - KHK
KW - propionate
UR - http://www.scopus.com/inward/record.url?scp=85067269703&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85067269703&partnerID=8YFLogxK
U2 - 10.1096/fj.201801526RR
DO - 10.1096/fj.201801526RR
M3 - Article
C2 - 30939042
AN - SCOPUS:85067269703
SN - 0892-6638
VL - 33
SP - 7126
EP - 7142
JO - FASEB Journal
JF - FASEB Journal
IS - 6
ER -