Cargando…
Changes in the gut microbiome associated with liver stiffness improvement in nonalcoholic steatohepatitis
BACKGROUND: Longitudinal studies are needed to decipher mechanistic links between the gut microbiome and nonalcoholic steatohepatitis (NASH). We examined shifts in the gut microbiome in persons with NASH with improvement in liver stiffness measurement (LSM) by magnetic resonance (MR) elastography. M...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121469/ https://www.ncbi.nlm.nih.gov/pubmed/35601801 http://dx.doi.org/10.1177/17562848221098243 |
_version_ | 1784711155325861888 |
---|---|
author | Sharpton, Suzanne R. Podlaha, Ondrej Chuang, Jen-Chieh Gindin, Yevgeniy Myers, Robert P. Loomba, Rohit |
author_facet | Sharpton, Suzanne R. Podlaha, Ondrej Chuang, Jen-Chieh Gindin, Yevgeniy Myers, Robert P. Loomba, Rohit |
author_sort | Sharpton, Suzanne R. |
collection | PubMed |
description | BACKGROUND: Longitudinal studies are needed to decipher mechanistic links between the gut microbiome and nonalcoholic steatohepatitis (NASH). We examined shifts in the gut microbiome in persons with NASH with improvement in liver stiffness measurement (LSM) by magnetic resonance (MR) elastography. METHODS: Gut microbial profiling was performed at baseline and study completion (24 weeks) using 16 S rRNA gene sequencing in 69 adults with biopsy-confirmed NASH and significant fibrosis (stages 2–3) enrolled in a multi-center randomized controlled trial evaluating selonsertib alone or in combination with simtuzumab. Differential abundance of bacterial taxa at baseline and end of study were examined in participants with and without longitudinal improvement in LSM. Gut microbial shifts that correlated with secondary outcomes, including reduction in MR imaging-derived proton density fat faction (MRI-PDFF) and histologic fibrosis regression were evaluated. Fecal samples from 32 healthy adults were profiled and genus-level multidimensional scaling was used to determine if microbial shifts in persons with NASH improvement represented a shift toward a healthy gut microbiome. RESULTS: Shifts in abundance of 36 bacterial taxa including Lactobacillus (log2(FC) = –4.51, FDR < 0.001), Enterococcus (log2(FC) = –6.72, FDR < 0.001), and Megasphaera (log2(FC) = 7.74, FDR < 0.001) were associated with improvement in LSM. Improvement in LSM was associated with microbial shifts toward healthy reference (p = 0.05). Significant shifts in 10 and 12 bacterial taxa were associated with improvement in LSM in addition to MRI-PDFF and fibrosis regression, respectively, indicating consistent taxonomic changes across multiple clinical endpoints. CONCLUSION: Longitudinal changes in the gut microbiota are observed in adults with NASH and clinical improvement and represent a shift toward a healthy microbiome. |
format | Online Article Text |
id | pubmed-9121469 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-91214692022-05-21 Changes in the gut microbiome associated with liver stiffness improvement in nonalcoholic steatohepatitis Sharpton, Suzanne R. Podlaha, Ondrej Chuang, Jen-Chieh Gindin, Yevgeniy Myers, Robert P. Loomba, Rohit Therap Adv Gastroenterol Original Research BACKGROUND: Longitudinal studies are needed to decipher mechanistic links between the gut microbiome and nonalcoholic steatohepatitis (NASH). We examined shifts in the gut microbiome in persons with NASH with improvement in liver stiffness measurement (LSM) by magnetic resonance (MR) elastography. METHODS: Gut microbial profiling was performed at baseline and study completion (24 weeks) using 16 S rRNA gene sequencing in 69 adults with biopsy-confirmed NASH and significant fibrosis (stages 2–3) enrolled in a multi-center randomized controlled trial evaluating selonsertib alone or in combination with simtuzumab. Differential abundance of bacterial taxa at baseline and end of study were examined in participants with and without longitudinal improvement in LSM. Gut microbial shifts that correlated with secondary outcomes, including reduction in MR imaging-derived proton density fat faction (MRI-PDFF) and histologic fibrosis regression were evaluated. Fecal samples from 32 healthy adults were profiled and genus-level multidimensional scaling was used to determine if microbial shifts in persons with NASH improvement represented a shift toward a healthy gut microbiome. RESULTS: Shifts in abundance of 36 bacterial taxa including Lactobacillus (log2(FC) = –4.51, FDR < 0.001), Enterococcus (log2(FC) = –6.72, FDR < 0.001), and Megasphaera (log2(FC) = 7.74, FDR < 0.001) were associated with improvement in LSM. Improvement in LSM was associated with microbial shifts toward healthy reference (p = 0.05). Significant shifts in 10 and 12 bacterial taxa were associated with improvement in LSM in addition to MRI-PDFF and fibrosis regression, respectively, indicating consistent taxonomic changes across multiple clinical endpoints. CONCLUSION: Longitudinal changes in the gut microbiota are observed in adults with NASH and clinical improvement and represent a shift toward a healthy microbiome. SAGE Publications 2022-05-18 /pmc/articles/PMC9121469/ /pubmed/35601801 http://dx.doi.org/10.1177/17562848221098243 Text en © The Author(s), 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Research Sharpton, Suzanne R. Podlaha, Ondrej Chuang, Jen-Chieh Gindin, Yevgeniy Myers, Robert P. Loomba, Rohit Changes in the gut microbiome associated with liver stiffness improvement in nonalcoholic steatohepatitis |
title | Changes in the gut microbiome associated with liver stiffness
improvement in nonalcoholic steatohepatitis |
title_full | Changes in the gut microbiome associated with liver stiffness
improvement in nonalcoholic steatohepatitis |
title_fullStr | Changes in the gut microbiome associated with liver stiffness
improvement in nonalcoholic steatohepatitis |
title_full_unstemmed | Changes in the gut microbiome associated with liver stiffness
improvement in nonalcoholic steatohepatitis |
title_short | Changes in the gut microbiome associated with liver stiffness
improvement in nonalcoholic steatohepatitis |
title_sort | changes in the gut microbiome associated with liver stiffness
improvement in nonalcoholic steatohepatitis |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121469/ https://www.ncbi.nlm.nih.gov/pubmed/35601801 http://dx.doi.org/10.1177/17562848221098243 |
work_keys_str_mv | AT sharptonsuzanner changesinthegutmicrobiomeassociatedwithliverstiffnessimprovementinnonalcoholicsteatohepatitis AT podlahaondrej changesinthegutmicrobiomeassociatedwithliverstiffnessimprovementinnonalcoholicsteatohepatitis AT chuangjenchieh changesinthegutmicrobiomeassociatedwithliverstiffnessimprovementinnonalcoholicsteatohepatitis AT gindinyevgeniy changesinthegutmicrobiomeassociatedwithliverstiffnessimprovementinnonalcoholicsteatohepatitis AT myersrobertp changesinthegutmicrobiomeassociatedwithliverstiffnessimprovementinnonalcoholicsteatohepatitis AT loombarohit changesinthegutmicrobiomeassociatedwithliverstiffnessimprovementinnonalcoholicsteatohepatitis |