The influence of liver transplantation on the interplay between gut microbiome and bile acid homeostasis in children with biliary atresia

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Reviewed Marked as Reviewed by Peace Sandy on 2024-2-9
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Waldner B, Aldrian D, Zöggeler T, Oberacher H, Oberhuber R, Schneeberger S, Messner F, Schneider AM, Kohlmaier B, Lanzersdorfer R, Huber WD, Entenmann A, Müller T, Vogel GF
Journal
Hepatology communications
Year
2023
BACKGROUND: Biliary atresia (BA) causes neonatal cholestasis and rapidly progresses into cirrhosis if left untreated. Kasai portoenterostomy may delay cirrhosis. BA remains among the most common indications for liver transplantation (LT) during childhood. Liver function and gut microbiome are interconnected. Disturbed liver function and enterohepatic signaling influence microbial diversity. We, herein, investigate the impact of LT and reestablishment of bile flow on gut microbiome-bile acid homeostasis in children with BA before (pre, n = 10), 3 months (post3m, n = 12), 12 months (post12m, n = 9), and more than 24 months (post24 + m, n = 12) after LT. METHODS: We analyzed the intestinal microbiome of BA patients before and after LT by 16S-rRNA-sequencing and bioinformatics analyses, and serum primary and secondary bile acid levels. RESULTS: The gut microbiome in BA patients exhibits a markedly reduced alpha diversity in pre (p = 0.015) and post3m group (p = 0.044), and approximated healthy control groups at later timepoints post12m (p = 1.0) and post24 + m (p = 0.74). Beta diversity analysis showed overall community structure similarities of pre and post3m (p = 0.675), but both differed from the post24 + m (p < 0.001). Longitudinal analysis of the composition of the gut microbiome revealed the Klebsiella genus to show increased abundance in the post24 + m group compared with an age-matched control (p = 0.029). Secondary bile acid production increased 2+ years after LT (p = 0.03). Multivariable associations of microbial communities and clinical metadata reveal several significant associations of microbial genera with tacrolimus and mycophenolate mofetil-based immunosuppressive regimens. CONCLUSIONS: In children with BA, the gut microbiome shows strongly reduced diversity before and shortly after LT, and approximates healthy controls at later timepoints. Changes in diversity correlate with altered secondary bile acid synthesis at 2+ years and with the selection of different immunosuppressants.

Experiment 1


Reviewed Marked as Reviewed by Peace Sandy on 2024-2-9

Curated date: 2023/11/17

Curator: Chinelsy

Revision editor(s): Chinelsy, Peace Sandy

Subjects

Location of subjects
Austria
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Biliary atresia atresia of bile duct,Atresia of bile ducts,atresia of bile ducts,biliary atresia,biliary atresia, congenital,congenital biliary atresia,isolated atresia of bile ducts,isolated biliary atresia,Non-syndromic biliary atresia,non-syndromic biliary atresia,Biliary atresia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Children with BA before - [pre]
Group 1 name Corresponds to the case (exposed) group for case-control studies
Post24 + m
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
The impact of LT and reestablishment of bile flow on gut microbiome–bile acid homeostasis in children with BA for more than 24 months (post24 + m) after liver transplantation (LT)
Group 0 sample size Number of subjects in the control (unexposed) group
10
Group 1 sample size Number of subjects in the case (exposed) group
12

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
LEfSe
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
Matched on Factors on which subjects have been matched on in a case-control study
age

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased
Simpson Estimator of species richness and species evenness: more weight on species evenness
increased
Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-2-9

Curated date: 2024/02/09

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: FIGURE 3

Description: Differential abundances and linear discriminant effect size analysis (LEfSe) of gut microbiota. (C) Cladogram of LEfSe analysis results of pre and post24 + m groups on the taxonomic order level. Over-representation of taxa is color-coded in red (post24 + m) and green (pre). Radiating circle depicts phylum to order level. (E) Barchart of LDA values with significantly different abundances to order level is shown comparing pre versus post24 + m, and healthy versus post24 +m

Abundance in Group 1: increased abundance in Post24 + m

NCBI Quality ControlLinks
Bacteroidales
Bacteroidia
Clostridia
Coriobacteriales
Coriobacteriia
Deltaproteobacteria
Desulfovibrionales
Erysipelotrichales
Erysipelotrichia
Eubacteriales

Revision editor(s): Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-2-9

Curated date: 2024/02/09

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Fig 3

Description: Differential abundances and linear discriminant effect size analysis (LEfSe) of gut microbiota. (C) Cladogram of LEfSe analysis results of pre and post24 + m groups on the taxonomic order level. Over-representation of taxa is color-coded in red (post24 + m) and green (pre). Radiating circle depicts phylum to order level. (E) Barchart of LDA values with significantly different abundances to order level is shown comparing pre versus post24 + m, and healthy versus post24 +m

Abundance in Group 1: decreased abundance in Post24 + m

NCBI Quality ControlLinks
Micrococcales
Campylobacterales
Bacillales
Lactobacillales
Bacilli

Revision editor(s): Peace Sandy

Experiment 2


Reviewed Marked as Reviewed by Peace Sandy on 2024-2-9

Curated date: 2024/02/09

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
post 24 + m Control
Group 0 sample size Number of subjects in the control (unexposed) group
19

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness
decreased

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-2-9

Curated date: 2024/02/09

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: FIGURE 3

Description: Differential abundances and linear discriminant effect size analysis (LEfSe) of gut microbiota. (D) Cladogram of LEfSe analysis results of post24 + m and age-matched control groups (p24 + m control) on the taxonomic order level. Over-representation of taxa is color-coded in red (p24 + m control) and green (post24 + m). Radiating circle depicts phylum to order level. Bar chart of LDA values with significantly different abundances to order level is shown comparing pre versus post24 + m, and healthy versus post24 +m in (F)

Abundance in Group 1: increased abundance in Post24 + m

NCBI Quality ControlLinks
Enterobacterales
Gammaproteobacteria

Revision editor(s): Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-2-9

Curated date: 2024/02/09

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Figure 3

Description: Differential abundances and linear discriminant effect size analysis (LEfSe) of gut microbiota. (D) Cladogram of LEfSe analysis results of post24 + m and age-matched control groups (p24 + m control) on the taxonomic order level. Over-representation of taxa is color-coded in red (p24 + m control) and green (post24 + m). Radiating circle depicts phylum to order level. Bar chart of LDA values with significantly different abundances to order level is shown comparing pre versus post24 + m, and healthy versus post24 +m in (F)

Abundance in Group 1: decreased abundance in Post24 + m

NCBI Quality ControlLinks
Bifidobacteriales
Actinomycetota
Eubacteriales
Clostridia

Revision editor(s): Peace Sandy