Diet-induced remission in chronic enteropathy is associated with altered microbial community structure and synthesis of secondary bile acids
Abstract Background The microbiome has been implicated in the initiation and persistence of inflammatory bowel disease. Despite the fact that diet is one of the most potent modulators of microbiome composition and function and that dietary intervention is the first-line therapy for treating pediatri...
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BMC
2019-08-01
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Online Access: | http://link.springer.com/article/10.1186/s40168-019-0740-4 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shuai Wang Rene Martins Megan C. Sullivan Elliot S. Friedman Ana M. Misic Ayah El-Fahmawi Elaine Cristina Pereira De Martinis Kevin O’Brien Ying Chen Charles Bradley Grace Zhang Alexander S. F. Berry Christopher A. Hunter Robert N. Baldassano Mark P. Rondeau Daniel P. Beiting |
spellingShingle |
Shuai Wang Rene Martins Megan C. Sullivan Elliot S. Friedman Ana M. Misic Ayah El-Fahmawi Elaine Cristina Pereira De Martinis Kevin O’Brien Ying Chen Charles Bradley Grace Zhang Alexander S. F. Berry Christopher A. Hunter Robert N. Baldassano Mark P. Rondeau Daniel P. Beiting Diet-induced remission in chronic enteropathy is associated with altered microbial community structure and synthesis of secondary bile acids Microbiome Chronic enteropathy Dietary therapy Microbiome Bile acids Canine Metabolomics |
author_facet |
Shuai Wang Rene Martins Megan C. Sullivan Elliot S. Friedman Ana M. Misic Ayah El-Fahmawi Elaine Cristina Pereira De Martinis Kevin O’Brien Ying Chen Charles Bradley Grace Zhang Alexander S. F. Berry Christopher A. Hunter Robert N. Baldassano Mark P. Rondeau Daniel P. Beiting |
author_sort |
Shuai Wang |
title |
Diet-induced remission in chronic enteropathy is associated with altered microbial community structure and synthesis of secondary bile acids |
title_short |
Diet-induced remission in chronic enteropathy is associated with altered microbial community structure and synthesis of secondary bile acids |
title_full |
Diet-induced remission in chronic enteropathy is associated with altered microbial community structure and synthesis of secondary bile acids |
title_fullStr |
Diet-induced remission in chronic enteropathy is associated with altered microbial community structure and synthesis of secondary bile acids |
title_full_unstemmed |
Diet-induced remission in chronic enteropathy is associated with altered microbial community structure and synthesis of secondary bile acids |
title_sort |
diet-induced remission in chronic enteropathy is associated with altered microbial community structure and synthesis of secondary bile acids |
publisher |
BMC |
series |
Microbiome |
issn |
2049-2618 |
publishDate |
2019-08-01 |
description |
Abstract Background The microbiome has been implicated in the initiation and persistence of inflammatory bowel disease. Despite the fact that diet is one of the most potent modulators of microbiome composition and function and that dietary intervention is the first-line therapy for treating pediatric Crohn’s disease, the relationships between diet-induced remission, enteropathy, and microbiome are poorly understood. Here, we leverage a naturally-occurring canine model of chronic inflammatory enteropathy that exhibits robust remission following nutritional therapy, to perform a longitudinal study that integrates clinical monitoring, 16S rRNA gene amplicon sequencing, metagenomic sequencing, metabolomic profiling, and whole genome sequencing to investigate the relationship between therapeutic diet, microbiome, and disease. Results We show that remission induced by a hydrolyzed protein diet is accompanied by alterations in microbial community structure marked by decreased abundance of pathobionts (e.g., Escherichia coli and Clostridium perfringens), reduced severity of dysbiosis, and increased levels of the secondary bile acids, lithocholic and deoxycholic acid. Physiologic levels of these bile acids inhibited the growth of E. coli and C. perfringens isolates, in vitro. Metagenomic analysis and whole genome sequencing identified the bile acid producer Clostridium hiranonis as elevated after dietary therapy and a likely source of secondary bile acids during remission. When C. hiranonis was administered to mice, levels of deoxycholic acid were preserved and pathology associated with DSS colitis was ameliorated. Finally, a closely related bile acid producer, Clostridium scindens, was associated with diet-induced remission in human pediatric Crohn’s disease. Conclusions These data highlight that remission induced by a hydrolyzed protein diet is associated with improved microbiota structure, an expansion of bile acid-producing clostridia, and increased levels of secondary bile acids. Our observations from clinical studies of exclusive enteral nutrition in human Crohn’s disease, along with our in vitro inhibition assays and in vivo studies in mice, suggest that this may be a conserved response to diet therapy with the potential to ameliorate disease. These findings provide insight into diet-induced remission of gastrointestinal disease and could help guide the rational design of more effective therapeutic diets. |
topic |
Chronic enteropathy Dietary therapy Microbiome Bile acids Canine Metabolomics |
url |
http://link.springer.com/article/10.1186/s40168-019-0740-4 |
work_keys_str_mv |
AT shuaiwang dietinducedremissioninchronicenteropathyisassociatedwithalteredmicrobialcommunitystructureandsynthesisofsecondarybileacids AT renemartins dietinducedremissioninchronicenteropathyisassociatedwithalteredmicrobialcommunitystructureandsynthesisofsecondarybileacids AT megancsullivan dietinducedremissioninchronicenteropathyisassociatedwithalteredmicrobialcommunitystructureandsynthesisofsecondarybileacids AT elliotsfriedman dietinducedremissioninchronicenteropathyisassociatedwithalteredmicrobialcommunitystructureandsynthesisofsecondarybileacids AT anammisic dietinducedremissioninchronicenteropathyisassociatedwithalteredmicrobialcommunitystructureandsynthesisofsecondarybileacids AT ayahelfahmawi dietinducedremissioninchronicenteropathyisassociatedwithalteredmicrobialcommunitystructureandsynthesisofsecondarybileacids AT elainecristinapereirademartinis dietinducedremissioninchronicenteropathyisassociatedwithalteredmicrobialcommunitystructureandsynthesisofsecondarybileacids AT kevinobrien dietinducedremissioninchronicenteropathyisassociatedwithalteredmicrobialcommunitystructureandsynthesisofsecondarybileacids AT yingchen dietinducedremissioninchronicenteropathyisassociatedwithalteredmicrobialcommunitystructureandsynthesisofsecondarybileacids AT charlesbradley dietinducedremissioninchronicenteropathyisassociatedwithalteredmicrobialcommunitystructureandsynthesisofsecondarybileacids AT gracezhang dietinducedremissioninchronicenteropathyisassociatedwithalteredmicrobialcommunitystructureandsynthesisofsecondarybileacids AT alexandersfberry dietinducedremissioninchronicenteropathyisassociatedwithalteredmicrobialcommunitystructureandsynthesisofsecondarybileacids AT christopherahunter dietinducedremissioninchronicenteropathyisassociatedwithalteredmicrobialcommunitystructureandsynthesisofsecondarybileacids AT robertnbaldassano dietinducedremissioninchronicenteropathyisassociatedwithalteredmicrobialcommunitystructureandsynthesisofsecondarybileacids AT markprondeau dietinducedremissioninchronicenteropathyisassociatedwithalteredmicrobialcommunitystructureandsynthesisofsecondarybileacids AT danielpbeiting dietinducedremissioninchronicenteropathyisassociatedwithalteredmicrobialcommunitystructureandsynthesisofsecondarybileacids |
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doaj-786a3f6b682b471a91a565c89b046ef02020-11-25T03:01:11ZengBMCMicrobiome2049-26182019-08-017112010.1186/s40168-019-0740-4Diet-induced remission in chronic enteropathy is associated with altered microbial community structure and synthesis of secondary bile acidsShuai Wang0Rene Martins1Megan C. Sullivan2Elliot S. Friedman3Ana M. Misic4Ayah El-Fahmawi5Elaine Cristina Pereira De Martinis6Kevin O’Brien7Ying Chen8Charles Bradley9Grace Zhang10Alexander S. F. Berry11Christopher A. Hunter12Robert N. Baldassano13Mark P. Rondeau14Daniel P. Beiting15Department of Pathobiology, School of Veterinary Medicine, University of PennsylvaniaDepartment of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of PennsylvaniaDepartment of Pathobiology, School of Veterinary Medicine, University of PennsylvaniaDivision of Gastroenterology, School of Medicine, University of PennsylvaniaDepartment of Pathobiology, School of Veterinary Medicine, University of PennsylvaniaDepartment of Pathobiology, School of Veterinary Medicine, University of PennsylvaniaFaculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São PauloDepartment of Pathobiology, School of Veterinary Medicine, University of PennsylvaniaDepartment of Pathobiology, School of Veterinary Medicine, University of PennsylvaniaDepartment of Pathobiology, School of Veterinary Medicine, University of PennsylvaniaDepartment of Pathobiology, School of Veterinary Medicine, University of PennsylvaniaDepartment of Pathobiology, School of Veterinary Medicine, University of PennsylvaniaDepartment of Pathobiology, School of Veterinary Medicine, University of PennsylvaniaDepartment of Pediatric Gastroenterology Hepatology and Nutrition, Children’s Hospital of PhiladelphiaDepartment of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of PennsylvaniaDepartment of Pathobiology, School of Veterinary Medicine, University of PennsylvaniaAbstract Background The microbiome has been implicated in the initiation and persistence of inflammatory bowel disease. Despite the fact that diet is one of the most potent modulators of microbiome composition and function and that dietary intervention is the first-line therapy for treating pediatric Crohn’s disease, the relationships between diet-induced remission, enteropathy, and microbiome are poorly understood. Here, we leverage a naturally-occurring canine model of chronic inflammatory enteropathy that exhibits robust remission following nutritional therapy, to perform a longitudinal study that integrates clinical monitoring, 16S rRNA gene amplicon sequencing, metagenomic sequencing, metabolomic profiling, and whole genome sequencing to investigate the relationship between therapeutic diet, microbiome, and disease. Results We show that remission induced by a hydrolyzed protein diet is accompanied by alterations in microbial community structure marked by decreased abundance of pathobionts (e.g., Escherichia coli and Clostridium perfringens), reduced severity of dysbiosis, and increased levels of the secondary bile acids, lithocholic and deoxycholic acid. Physiologic levels of these bile acids inhibited the growth of E. coli and C. perfringens isolates, in vitro. Metagenomic analysis and whole genome sequencing identified the bile acid producer Clostridium hiranonis as elevated after dietary therapy and a likely source of secondary bile acids during remission. When C. hiranonis was administered to mice, levels of deoxycholic acid were preserved and pathology associated with DSS colitis was ameliorated. Finally, a closely related bile acid producer, Clostridium scindens, was associated with diet-induced remission in human pediatric Crohn’s disease. Conclusions These data highlight that remission induced by a hydrolyzed protein diet is associated with improved microbiota structure, an expansion of bile acid-producing clostridia, and increased levels of secondary bile acids. Our observations from clinical studies of exclusive enteral nutrition in human Crohn’s disease, along with our in vitro inhibition assays and in vivo studies in mice, suggest that this may be a conserved response to diet therapy with the potential to ameliorate disease. These findings provide insight into diet-induced remission of gastrointestinal disease and could help guide the rational design of more effective therapeutic diets.http://link.springer.com/article/10.1186/s40168-019-0740-4Chronic enteropathyDietary therapyMicrobiomeBile acidsCanineMetabolomics |