Dietary fiber-based regulation of bile salt hydrolase activity in the gut microbiota and its relevance to human disease
Complications of short bowel syndrome (SBS) include malabsorption and bacterial overgrowth, requiring prolonged dependence on parenteral nutrition (PN). We hypothesized that the intolerance of whole food in some SBS patients might be due to the effect of dietary fiber on the gut microbiome. Shotgun...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2022-12-01
|
| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2022.2083417 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849763428142415872 |
|---|---|
| author | Arthur Kastl Wenjing Zong Victoria M. Gershuni Elliot S. Friedman Ceylan Tanes Adoma Boateng William J. Mitchell Kathleen O’Connor Kyle Bittinger Natalie A. Terry Christina Bales Lindsey Albenberg Gary D. Wu |
| author_facet | Arthur Kastl Wenjing Zong Victoria M. Gershuni Elliot S. Friedman Ceylan Tanes Adoma Boateng William J. Mitchell Kathleen O’Connor Kyle Bittinger Natalie A. Terry Christina Bales Lindsey Albenberg Gary D. Wu |
| author_sort | Arthur Kastl |
| collection | DOAJ |
| description | Complications of short bowel syndrome (SBS) include malabsorption and bacterial overgrowth, requiring prolonged dependence on parenteral nutrition (PN). We hypothesized that the intolerance of whole food in some SBS patients might be due to the effect of dietary fiber on the gut microbiome. Shotgun metagenomic sequencing and targeted metabolomics were performed using biospecimens collected from 55 children with SBS and a murine dietary fiber model. Bioinformatic analyses were performed on these datasets as well as from a healthy human dietary intervention study. Compared to healthy controls, the gut microbiota in SBS had lower diversity and increased Proteobacteria, a pattern most pronounced in children on PN and inversely correlated with whole food consumption. Whole food intake correlated with increased glycoside hydrolases (GH) and bile salt hydrolases (BSH) with reduced fecal conjugated bile acids suggesting that dietary fiber regulates BSH activity via GHs. Mechanistic evidence supporting this notion was generated via fecal and plasma bile acid profiling in a healthy human fiber-free dietary intervention study as well as in a dietary fiber mouse experiment. Gaussian mixture modeling of fecal bile acids was used to identify three clinically relevant SBS phenotypes. Dietary fiber is associated with bile acid deconjugation likely via an interaction between gut microbiota BSHs and GHs in the small intestine, which may lead to whole food intolerance in patients with SBS. This mechanism not only has potential utility in clinical phenotyping and targeted therapeutics in SBS based on bile acid metabolism but may have relevance to other intestinal disease states. |
| format | Article |
| id | doaj-art-a9b52c19c2ba4c99bafd0df8dcf7a6da |
| institution | DOAJ |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-a9b52c19c2ba4c99bafd0df8dcf7a6da2025-08-20T03:05:25ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2083417Dietary fiber-based regulation of bile salt hydrolase activity in the gut microbiota and its relevance to human diseaseArthur Kastl0Wenjing Zong1Victoria M. Gershuni2Elliot S. Friedman3Ceylan Tanes4Adoma Boateng5William J. Mitchell6Kathleen O’Connor7Kyle Bittinger8Natalie A. Terry9Christina Bales10Lindsey Albenberg11Gary D. Wu12Division of Gastroenterology, Hepatology, and Nutrition, the Children’s Hospital of Philadelphia, Philadelphia, PA, USADivision of Gastroenterology, Hepatology, and Nutrition, the Children’s Hospital of Philadelphia, Philadelphia, PA, USADepartment of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USADivision of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USADivision of Gastroenterology, Hepatology, and Nutrition, the Children’s Hospital of Philadelphia, Philadelphia, PA, USADivision of Gastroenterology, Hepatology, and Nutrition, the Children’s Hospital of Philadelphia, Philadelphia, PA, USADivision of Gastroenterology, Hepatology, and Nutrition, the Children’s Hospital of Philadelphia, Philadelphia, PA, USADivision of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USADivision of Gastroenterology, Hepatology, and Nutrition, the Children’s Hospital of Philadelphia, Philadelphia, PA, USADivision of Gastroenterology, Hepatology, and Nutrition, the Children’s Hospital of Philadelphia, Philadelphia, PA, USADivision of Gastroenterology, Hepatology, and Nutrition, the Children’s Hospital of Philadelphia, Philadelphia, PA, USADivision of Gastroenterology, Hepatology, and Nutrition, the Children’s Hospital of Philadelphia, Philadelphia, PA, USADivision of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USAComplications of short bowel syndrome (SBS) include malabsorption and bacterial overgrowth, requiring prolonged dependence on parenteral nutrition (PN). We hypothesized that the intolerance of whole food in some SBS patients might be due to the effect of dietary fiber on the gut microbiome. Shotgun metagenomic sequencing and targeted metabolomics were performed using biospecimens collected from 55 children with SBS and a murine dietary fiber model. Bioinformatic analyses were performed on these datasets as well as from a healthy human dietary intervention study. Compared to healthy controls, the gut microbiota in SBS had lower diversity and increased Proteobacteria, a pattern most pronounced in children on PN and inversely correlated with whole food consumption. Whole food intake correlated with increased glycoside hydrolases (GH) and bile salt hydrolases (BSH) with reduced fecal conjugated bile acids suggesting that dietary fiber regulates BSH activity via GHs. Mechanistic evidence supporting this notion was generated via fecal and plasma bile acid profiling in a healthy human fiber-free dietary intervention study as well as in a dietary fiber mouse experiment. Gaussian mixture modeling of fecal bile acids was used to identify three clinically relevant SBS phenotypes. Dietary fiber is associated with bile acid deconjugation likely via an interaction between gut microbiota BSHs and GHs in the small intestine, which may lead to whole food intolerance in patients with SBS. This mechanism not only has potential utility in clinical phenotyping and targeted therapeutics in SBS based on bile acid metabolism but may have relevance to other intestinal disease states.https://www.tandfonline.com/doi/10.1080/19490976.2022.2083417Short bowel syndromeparenteral nutritionmicrobiotabile acids |
| spellingShingle | Arthur Kastl Wenjing Zong Victoria M. Gershuni Elliot S. Friedman Ceylan Tanes Adoma Boateng William J. Mitchell Kathleen O’Connor Kyle Bittinger Natalie A. Terry Christina Bales Lindsey Albenberg Gary D. Wu Dietary fiber-based regulation of bile salt hydrolase activity in the gut microbiota and its relevance to human disease Gut Microbes Short bowel syndrome parenteral nutrition microbiota bile acids |
| title | Dietary fiber-based regulation of bile salt hydrolase activity in the gut microbiota and its relevance to human disease |
| title_full | Dietary fiber-based regulation of bile salt hydrolase activity in the gut microbiota and its relevance to human disease |
| title_fullStr | Dietary fiber-based regulation of bile salt hydrolase activity in the gut microbiota and its relevance to human disease |
| title_full_unstemmed | Dietary fiber-based regulation of bile salt hydrolase activity in the gut microbiota and its relevance to human disease |
| title_short | Dietary fiber-based regulation of bile salt hydrolase activity in the gut microbiota and its relevance to human disease |
| title_sort | dietary fiber based regulation of bile salt hydrolase activity in the gut microbiota and its relevance to human disease |
| topic | Short bowel syndrome parenteral nutrition microbiota bile acids |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2022.2083417 |
| work_keys_str_mv | AT arthurkastl dietaryfiberbasedregulationofbilesalthydrolaseactivityinthegutmicrobiotaanditsrelevancetohumandisease AT wenjingzong dietaryfiberbasedregulationofbilesalthydrolaseactivityinthegutmicrobiotaanditsrelevancetohumandisease AT victoriamgershuni dietaryfiberbasedregulationofbilesalthydrolaseactivityinthegutmicrobiotaanditsrelevancetohumandisease AT elliotsfriedman dietaryfiberbasedregulationofbilesalthydrolaseactivityinthegutmicrobiotaanditsrelevancetohumandisease AT ceylantanes dietaryfiberbasedregulationofbilesalthydrolaseactivityinthegutmicrobiotaanditsrelevancetohumandisease AT adomaboateng dietaryfiberbasedregulationofbilesalthydrolaseactivityinthegutmicrobiotaanditsrelevancetohumandisease AT williamjmitchell dietaryfiberbasedregulationofbilesalthydrolaseactivityinthegutmicrobiotaanditsrelevancetohumandisease AT kathleenoconnor dietaryfiberbasedregulationofbilesalthydrolaseactivityinthegutmicrobiotaanditsrelevancetohumandisease AT kylebittinger dietaryfiberbasedregulationofbilesalthydrolaseactivityinthegutmicrobiotaanditsrelevancetohumandisease AT natalieaterry dietaryfiberbasedregulationofbilesalthydrolaseactivityinthegutmicrobiotaanditsrelevancetohumandisease AT christinabales dietaryfiberbasedregulationofbilesalthydrolaseactivityinthegutmicrobiotaanditsrelevancetohumandisease AT lindseyalbenberg dietaryfiberbasedregulationofbilesalthydrolaseactivityinthegutmicrobiotaanditsrelevancetohumandisease AT garydwu dietaryfiberbasedregulationofbilesalthydrolaseactivityinthegutmicrobiotaanditsrelevancetohumandisease |