Donor fecal microbiota transplantation alters gut microbiota and metabolites in obese individuals with steatohepatitis
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Donor fecal microbiota transplantation alters gut microbiota and metabolites in obese individuals with steatohepatitis. / Witjes, Julia J; Smits, Loek P; Pekmez, Ceyda Tugba; Prodan, Andrei; Meijnikman, Abraham S; Troelstra, Marian A; Bouter, Kristien E C; Herrema, Hilde; Levin, Evgeni; Holleboom, Adriaan G; Winkelmeijer, Maaike; Beuers, Ulrich H; van Lienden, Krijn; Aron-Wisnewky, Judith; Mannisto, Ville; Bergman, Jacques J; Runge, Jurgen H; Nederveen, Aart J; Dragsted, Lars Ove; Konstanti, Prokopis; Zoetendal, Erwin G; de Vos, Willem; Verheij, Joanne; Groen, Albert K; Nieuwdorp, Max.
In: Hepatology Communications, Vol. 4, No. 11, 2020, p. 1578-1590.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Donor fecal microbiota transplantation alters gut microbiota and metabolites in obese individuals with steatohepatitis
AU - Witjes, Julia J
AU - Smits, Loek P
AU - Pekmez, Ceyda Tugba
AU - Prodan, Andrei
AU - Meijnikman, Abraham S
AU - Troelstra, Marian A
AU - Bouter, Kristien E C
AU - Herrema, Hilde
AU - Levin, Evgeni
AU - Holleboom, Adriaan G
AU - Winkelmeijer, Maaike
AU - Beuers, Ulrich H
AU - van Lienden, Krijn
AU - Aron-Wisnewky, Judith
AU - Mannisto, Ville
AU - Bergman, Jacques J
AU - Runge, Jurgen H
AU - Nederveen, Aart J
AU - Dragsted, Lars Ove
AU - Konstanti, Prokopis
AU - Zoetendal, Erwin G
AU - de Vos, Willem
AU - Verheij, Joanne
AU - Groen, Albert K
AU - Nieuwdorp, Max
N1 - © 2020 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.1002/hep4.1601
DO - 10.1002/hep4.1601
M3 - Journal article
C2 - 33163830
VL - 4
SP - 1578
EP - 1590
JO - Hepatology Communications
JF - Hepatology Communications
SN - 2471-254X
IS - 11
ER -
ID: 251309348