Exclusive enteral nutrition mediates gut microbial and metabolic changes that are associated with remission in children with Crohn's disease

被引:93
作者
Diederen, Kay [1 ,2 ,3 ]
Li, Jia, V [4 ]
Donachie, Gillian E. [6 ]
de Meij, Tim G. [1 ,2 ]
de Waart, Dirk R. [3 ]
Hakvoort, Theodorus B. M. [3 ]
Kindermann, Angelika [1 ,2 ]
Wagner, Josef [7 ]
Auyeung, Victoria [4 ,5 ]
te Velde, Anje A. [3 ]
Heinsbroek, Sigrid E. M. [3 ]
Benninga, Marc A. [1 ,2 ]
Kinross, James [4 ,5 ]
Walker, Alan W. [6 ]
de Jonge, Wouter J. [3 ]
Seppen, Jurgen [3 ]
机构
[1] Locat AMC, Amsterdam UMC, Dept Pediat Gastroenterol & Nutr, Amsterdam, Netherlands
[2] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands
[3] Locat AMC, Amsterdam UMC, Tytgat Inst Liver & Intestinal Res, Meibergdreef 69, NL-1105 BK Amsterdam, Netherlands
[4] Imperial Coll London, Div Digest Dis, Dept Metab Digest & Reprod, London, England
[5] Imperial Coll London, Dept Surg & Canc, London, England
[6] Univ Aberdeen, Rowett Inst, Aberdeen, Scotland
[7] Wellcome Sanger Inst, Pathogen Genom Grp, Hinxton, Cambs, England
基金
欧盟地平线“2020”; 英国惠康基金; 欧洲研究理事会;
关键词
INFLAMMATORY-BOWEL-DISEASE; DEXTRAN SULFATE SODIUM; INTESTINAL MICROBIOTA; NMR-SPECTROSCOPY; L-CARNITINE; RECEPTOR; COLITIS; TGR5; CORTICOSTEROIDS; IDENTIFICATION;
D O I
10.1038/s41598-020-75306-z
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
A nutritional intervention, exclusive enteral nutrition (EEN) can induce remission in patients with pediatric Crohn's disease (CD). We characterized changes in the fecal microbiota and metabolome to identify the mechanism of EEN. Feces of 43 children were collected prior, during and after EEN. Microbiota and metabolites were analyzed by 16S rRNA gene amplicon sequencing and NMR. Selected metabolites were evaluated in relevant model systems. Microbiota and metabolome of patients with CD and controls were different at all time points. Amino acids, primary bile salts, trimethylamine and cadaverine were elevated in patients with CD. Microbiota and metabolome differed between responders and non-responders prior to EEN. EEN decreased microbiota diversity and reduced amino acids, trimethylamine and cadaverine towards control levels. Patients with CD had reduced microbial metabolism of bile acids that partially normalized during EEN. Trimethylamine and cadaverine inhibited intestinal cell growth. TMA and cadaverine inhibited LPS-stimulated TNF-alpha and IL-6 secretion by primary human monocytes. A diet rich in free amino acids worsened inflammation in the DSS model of intestinal inflammation. Trimethylamine, cadaverine, bile salts and amino acids could play a role in the mechanism by which EEN induces remission. Prior to EEN, microbiota and metabolome are different between responders and non-responders.
引用
收藏
页数:17
相关论文
共 82 条
[1]
Dynamic and label-free cell-based assays using the real-time cell electronic sensing system [J].
Atienza, Josephine M. ;
Yu, Naichen ;
Kirstein, Shelli L. ;
Xi, Biao ;
Wang, Xiaobo ;
Xu, Xiao ;
Abassi, Yama A. .
ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES, 2006, 4 (05) :597-607
[2]
In vivo imaging of colitis and colon cancer development in mice using high resolution chromoendoscopy [J].
Becker, C ;
Fantini, MC ;
Wirtz, S ;
Nikolaev, A ;
Kiesslich, R ;
Lehr, HA ;
Galle, PR ;
Neurath, MF .
GUT, 2005, 54 (07) :950-954
[3]
Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts [J].
Beckonert, Olaf ;
Keun, Hector C. ;
Ebbels, Timothy M. D. ;
Bundy, Jacob G. ;
Holmes, Elaine ;
Lindon, John C. ;
Nicholson, Jeremy K. .
NATURE PROTOCOLS, 2007, 2 (11) :2692-2703
[4]
CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[5]
Metabonomics of human fecal extracts characterize ulcerative colitis, Crohn's disease and healthy individuals [J].
Bjerrum, Jacob Tveiten ;
Wang, Yulan ;
Hao, Fuhua ;
Coskun, Mehmet ;
Ludwig, Christian ;
Guenther, Ulrich ;
Nielsen, Ole Haagen .
METABOLOMICS, 2015, 11 (01) :122-133
[6]
Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn's disease: A randomized controlled open-label trial [J].
Borrelli, Osvaldo ;
Cordischi, Letizia ;
Cirulli, Manuela ;
Paganelli, Massimiliano ;
Labalestra, Valeria ;
Uccini, Stefania ;
Russo, Paolo M. ;
Cucchiara, Salvatore .
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2006, 4 (06) :744-753
[7]
Statistical total correlation spectroscopy:: An exploratory approach for latent biomarker identification from metabolic 1H NMR data sets [J].
Cloarec, O ;
Dumas, ME ;
Craig, A ;
Barton, RH ;
Trygg, J ;
Hudson, J ;
Blancher, C ;
Gauguier, D ;
Lindon, JC ;
Holmes, E ;
Nicholson, J .
ANALYTICAL CHEMISTRY, 2005, 77 (05) :1282-1289
[8]
Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease [J].
D'Haens, Geert ;
Ferrante, Marc ;
Vermeire, Severine ;
Baert, Filip ;
Noman, Maja ;
Moortgat, Liesbeth ;
Geens, Patricia ;
Iwens, Doreen ;
Aerden, Isolde ;
Van Assche, Gert ;
Van Olmen, Gust ;
Rutgeerts, Paul .
INFLAMMATORY BOWEL DISEASES, 2012, 18 (12) :2218-2224
[9]
Dietary Uncoupling of Gut Microbiota and Energy Harvesting from Obesity and Glucose Tolerance in Mice [J].
Dalby, Matthew J. ;
Ross, Alexander W. ;
Walker, Alan W. ;
Morgan, Peter J. .
CELL REPORTS, 2017, 21 (06) :1521-1533
[10]
Variability of core microbiota in newly diagnosed treatment-naive paediatric inflammatory bowel disease patients [J].
de Meij, T. G. J. ;
de Groot, E. F. J. ;
Peeters, C. F. W. ;
de Boer, N. K. H. ;
Kneepkens, C. M. F. ;
Eck, A. ;
Benninga, M. A. ;
Savelkoul, P. H. M. ;
van Bodegraven, A. A. ;
Budding, A. E. .
PLOS ONE, 2018, 13 (08)