Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis
The intestinal microbiota has been linked to the development and prevalence of steatohepatitis in humans. Interestingly, steatohepatitis is significantly lower in individuals taking a plant‐based, low‐animal‐protein diet, which is thought to be mediated by gut microbiota. However, data on causality...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Health/LWW
2020-11-01
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| Series: | Hepatology Communications |
| Online Access: | https://doi.org/10.1002/hep4.1601 |
| _version_ | 1828046704096575488 |
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| author | Julia J. Witjes Loek P. Smits Ceyda T. Pekmez Andrei Prodan Abraham S. Meijnikman Marian A. Troelstra Kristien E.C. Bouter Hilde Herrema Evgeni Levin Adriaan G. Holleboom Maaike Winkelmeijer Ulrich H. Beuers Krijn vanLienden Judith Aron‐Wisnewky Ville Mannisto Jacques J. Bergman Jurgen H. Runge Aart J. Nederveen Lars O. Dragsted Prokopis Konstanti Erwin G. Zoetendal Willem deVos Joanne Verheij Albert K. Groen Max Nieuwdorp |
| author_facet | Julia J. Witjes Loek P. Smits Ceyda T. Pekmez Andrei Prodan Abraham S. Meijnikman Marian A. Troelstra Kristien E.C. Bouter Hilde Herrema Evgeni Levin Adriaan G. Holleboom Maaike Winkelmeijer Ulrich H. Beuers Krijn vanLienden Judith Aron‐Wisnewky Ville Mannisto Jacques J. Bergman Jurgen H. Runge Aart J. Nederveen Lars O. Dragsted Prokopis Konstanti Erwin G. Zoetendal Willem deVos Joanne Verheij Albert K. Groen Max Nieuwdorp |
| author_sort | Julia J. Witjes |
| collection | DOAJ |
| description | The intestinal microbiota has been linked to the development and prevalence of steatohepatitis in humans. Interestingly, steatohepatitis is significantly lower in individuals taking a plant‐based, low‐animal‐protein diet, which is thought to be mediated by gut microbiota. However, data on causality between these observations in humans is scarce. In this regard, fecal microbiota transplantation (FMT) using healthy donors is safe and is capable of changing microbial composition in human disease. We therefore performed a double‐blind randomized controlled proof‐of‐principle study in which individuals with hepatic steatosis on ultrasound were randomized to two study arms: lean vegan donor (allogenic n = 10) or own (autologous n = 11) FMT. Both were performed three times at 8‐week intervals. A liver biopsy was performed at baseline and after 24 weeks in every subject to determine histopathology (Nonalcoholic Steatohepatitis Clinical Research Network) classification and changes in hepatic gene expression based on RNA sequencing. Secondary outcome parameters were changes in intestinal microbiota composition and fasting plasma metabolomics. We observed a trend toward improved necro‐inflammatory histology, and found significant changes in expression of hepatic genes involved in inflammation and lipid metabolism following allogenic FMT. Intestinal microbial community structure changed following allogenic FMT, which was associated with changes in plasma metabolites as well as markers of . Conclusion: Allogenic FMT using lean vegan donors in individuals with hepatic steatosis shows an effect on intestinal microbiota composition, which is associated with beneficial changes in plasma metabolites and markers of steatohepatitis. |
| first_indexed | 2024-04-10T18:29:41Z |
| format | Article |
| id | doaj.art-3a828877c8044547b262b85e4264f55c |
| institution | Directory Open Access Journal |
| issn | 2471-254X |
| language | English |
| last_indexed | 2024-04-10T18:29:41Z |
| publishDate | 2020-11-01 |
| publisher | Wolters Kluwer Health/LWW |
| record_format | Article |
| series | Hepatology Communications |
| spelling | doaj.art-3a828877c8044547b262b85e4264f55c2023-02-02T04:41:37ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2020-11-014111578159010.1002/hep4.1601Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With SteatohepatitisJulia J. Witjes0Loek P. Smits1Ceyda T. Pekmez2Andrei Prodan3Abraham S. Meijnikman4Marian A. Troelstra5Kristien E.C. Bouter6Hilde Herrema7Evgeni Levin8Adriaan G. Holleboom9Maaike Winkelmeijer10Ulrich H. Beuers11Krijn vanLienden12Judith Aron‐Wisnewky13Ville Mannisto14Jacques J. Bergman15Jurgen H. Runge16Aart J. Nederveen17Lars O. Dragsted18Prokopis Konstanti19Erwin G. Zoetendal20Willem deVos21Joanne Verheij22Albert K. Groen23Max Nieuwdorp24Department of Internal and Vascular Medicine Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Internal and Vascular Medicine Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Nutrition, Exercise and Sports University of Copenhagen Copenhagen DenmarkDepartment of Internal and Vascular Medicine Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Internal and Vascular Medicine Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Radiology & Nuclear Medicine Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Internal and Vascular Medicine Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Internal and Vascular Medicine Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Internal and Vascular Medicine Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Internal and Vascular Medicine Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Internal and Vascular Medicine Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Gastroenterology and Hepatology Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Radiology & Nuclear Medicine Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Internal and Vascular Medicine Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Internal and Vascular Medicine Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Gastroenterology and Hepatology Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Radiology & Nuclear Medicine Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Radiology & Nuclear Medicine Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Nutrition, Exercise and Sports University of Copenhagen Copenhagen DenmarkLaboratory of Microbiology Wageningen University Wageningen the NetherlandsLaboratory of Microbiology Wageningen University Wageningen the NetherlandsLaboratory of Microbiology Wageningen University Wageningen the NetherlandsDepartment of Pathology Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Internal and Vascular Medicine Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsDepartment of Internal and Vascular Medicine Amsterdam University Medical CentersLocation AMC Amsterdam the NetherlandsThe intestinal microbiota has been linked to the development and prevalence of steatohepatitis in humans. Interestingly, steatohepatitis is significantly lower in individuals taking a plant‐based, low‐animal‐protein diet, which is thought to be mediated by gut microbiota. However, data on causality between these observations in humans is scarce. In this regard, fecal microbiota transplantation (FMT) using healthy donors is safe and is capable of changing microbial composition in human disease. We therefore performed a double‐blind randomized controlled proof‐of‐principle study in which individuals with hepatic steatosis on ultrasound were randomized to two study arms: lean vegan donor (allogenic n = 10) or own (autologous n = 11) FMT. Both were performed three times at 8‐week intervals. A liver biopsy was performed at baseline and after 24 weeks in every subject to determine histopathology (Nonalcoholic Steatohepatitis Clinical Research Network) classification and changes in hepatic gene expression based on RNA sequencing. Secondary outcome parameters were changes in intestinal microbiota composition and fasting plasma metabolomics. We observed a trend toward improved necro‐inflammatory histology, and found significant changes in expression of hepatic genes involved in inflammation and lipid metabolism following allogenic FMT. Intestinal microbial community structure changed following allogenic FMT, which was associated with changes in plasma metabolites as well as markers of . Conclusion: Allogenic FMT using lean vegan donors in individuals with hepatic steatosis shows an effect on intestinal microbiota composition, which is associated with beneficial changes in plasma metabolites and markers of steatohepatitis.https://doi.org/10.1002/hep4.1601 |
| spellingShingle | Julia J. Witjes Loek P. Smits Ceyda T. Pekmez Andrei Prodan Abraham S. Meijnikman Marian A. Troelstra Kristien E.C. Bouter Hilde Herrema Evgeni Levin Adriaan G. Holleboom Maaike Winkelmeijer Ulrich H. Beuers Krijn vanLienden Judith Aron‐Wisnewky Ville Mannisto Jacques J. Bergman Jurgen H. Runge Aart J. Nederveen Lars O. Dragsted Prokopis Konstanti Erwin G. Zoetendal Willem deVos Joanne Verheij Albert K. Groen Max Nieuwdorp Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis Hepatology Communications |
| title | Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis |
| title_full | Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis |
| title_fullStr | Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis |
| title_full_unstemmed | Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis |
| title_short | Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis |
| title_sort | donor fecal microbiota transplantation alters gut microbiota and metabolites in obese individuals with steatohepatitis |
| url | https://doi.org/10.1002/hep4.1601 |
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