Role of intestinal flora in the development of nonalcoholic fatty liver disease in children

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Reviewed Marked as Reviewed by Svetlana up on 2024-7-26
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Zhang J, Shi M, Zhao C, Liang G, Li C, Ge X, Pei C, Kong Y, Li D, Yang W, Cao B, Fu L, Yan Y, Wu J, Zhou J, Fang Y, Meng X, Li Y, Wang L
Journal
Microbiology spectrum
Year
2024
Keywords:
BMI, NAFLD, NASH, children, gut microbiota, metabolism
In China, 45% of adolescents with obesity develop fatty liver disease, a condition that increases the long-term risk of developing cirrhosis and liver cancer. Although the factors triggering nonalcoholic fatty liver disease (NAFLD) vary in children, the composition of intestinal microflora has been found to play an increasingly important role. However, evidence is limited on the prevalence of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) in Chinese children. Therefore, this study aimed to evaluate the fecal microbiome of Chinese children with NAFLD and further analyze the potential of flora in regulating NAFLD-related symptoms and metabolic functions. Specifically, the study applied a 16S rRNA and metagenomic sequencing to the fecal samples of pediatric patients with NAFLD, NASH, and NAFL, as well as healthy controls, to explore the correlation among NAFLD-related indexes, metabolic pathways, and gut flora. The findings showed that some fecal microbiota had a negative correlation with body mass index, and various NAFLD-related bacteria, including Lachnoclostridium, Escherichia-Shigella, and Faecalibacterium prausnitzii, were detected. Consequently, the study concluded that the variation in gut microbiota might be more important in improving NAFLD/NASH compared with single species, providing a microbiota diagnostic profile of NAFLD/NASH.IMPORTANCEThis study aims to characterize the gut microbiota in Chinese children with nonalcoholic fatty liver disease (NAFLD) through 16S rRNA and metagenomic sequencing. The results highlight the association between fecal microbiota and NAFLD in Chinese children, demonstrating distinct characteristics compared to adults and children from other countries. Based on the sequencing data from our cohort's fecal samples, we propose a microbiota model with a high area under the curve for distinguishing between NAFLD and healthy individuals. Furthermore, our follow-up study reveals that changes in the relative abundance of microbial biomarkers in this model are consistent with variations in patients' body mass index. These findings suggest the potential utility of the microbiota model and microbial biomarkers for diagnosing and treating NAFLD in children.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2024-7-26

Curated date: 2024/03/14

Curator: Scholastica

Revision editor(s): Scholastica

Subjects

Location of subjects
China
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
Non-alcoholic fatty liver disease fatty liver disease, nonalcoholic,fatty liver disease, nonalcoholic, susceptibility to, 1,liver disease, alcoholic, susceptibility to, 1,NAFLD - Nonalcoholic Fatty Liver Disease,NAFLD - nonalcoholic fatty liver disease,NAFLD1,non-alcoholic fatty liver,non-alcoholic fatty liver disease,Nonalcoholic Fatty Liver Disease,nonalcoholic fatty liver disease,Non-alcoholic fatty liver disease
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
Non-alcoholic fatty liver disease (NAFLD)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Pediatric patients with non-alcoholic fatty liver disease (NAFLD) whose body mass index (BMI) was higher than the 95th percentile and defined through a clinical evaluation and liver ultrasonography
Group 0 sample size Number of subjects in the control (unexposed) group
35
Group 1 sample size Number of subjects in the case (exposed) group
79
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
2 months

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
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-7-26

Curated date: 2024/03/14

Curator: Scholastica

Revision editor(s): Scholastica

Source: Fig 3

Description: Multiple bacterial species with significantly different abundance found in the intestinal flora of patients with non-alcoholic fatty liver disease (NAFLD) versus healthy controls (HCs)

Abundance in Group 1: increased abundance in Non-alcoholic fatty liver disease (NAFLD)

NCBI Quality ControlLinks
Alcaligenaceae
Bacilli
Bacteria
Betaproteobacteria
Burkholderiales
Butyricicoccus
Enterobacterales
Enterobacteriaceae
Escherichia/Shigella sp.
Flavonifractor
Fusobacteriales
Fusobacteriia
Klebsiella
Lachnoclostridium
Lachnospiraceae
Lactobacillaceae
Lactobacillales
Lactobacillus
Mediterraneibacter gnavus
Pseudomonadota
Tyzzerella
Tyzzerella sp.
unclassified Lachnospiraceae

Revision editor(s): Scholastica

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-7-26

Curated date: 2024/03/14

Curator: Scholastica

Revision editor(s): Scholastica, Ayibatari

Source: Fig 3

Description: Multiple bacterial species with significantly different abundance found in the intestinal flora of patients with non-alcoholic fatty liver disease (NAFLD) versus healthy controls (HCs)

Abundance in Group 1: decreased abundance in Non-alcoholic fatty liver disease (NAFLD)

NCBI Quality ControlLinks
Anaerostipes
Archaea
Barnesiella
Bifidobacteriaceae
Bifidobacteriales
Christensenellaceae
Christensenellaceae
Comamonadaceae
Comamonas
Coprococcus
Dialister
Erysipelotrichaceae
Erysipelotrichales
Erysipelotrichia
Eubacterium coprostanoligenes
Eubacterium ventriosum
Methanobacteriota
Faecalibacterium
Fusicatenibacter
Haemophilus
Megamonas
Megasphaera
Methanobacteria
Methanobacteriaceae
Methanobacteriales
Methanobrevibacter
Oscillospiraceae
Paraprevotella
Pasteurellaceae
Pasteurellales
Peptoclostridium
Peptostreptococcaceae
Prevotella
Prevotella sp. 2-3
Prevotellaceae
Ruminiclostridium
Ruminococcaceae sp. B_A14
Ruminococcus
Streptococcaceae
Streptococcus
Veillonellaceae
uncultured Erysipelotrichaceae bacterium
uncultured Oscillospiraceae bacterium
uncultured bacterium
Christensenellaceae R-7Christensenellaceae R-7
Lachnospiraceae ND3007Lachnospiraceae ND3007
Prevotellaceae UCG-001Prevotellaceae UCG-001
Lachnospiraceae UCG-003Lachnospiraceae UCG-003
Ruminococcaceae UCG-010Ruminococcaceae UCG-010
PrevotellaceaeUCG_001PrevotellaceaeUCG_001
Prevotellaceae Ga6A1Prevotellaceae Ga6A1

Revision editor(s): Scholastica, Ayibatari

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2024-7-26

Curated date: 2024/03/15

Curator: Scholastica

Revision editor(s): Scholastica

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Non-alcoholic steatohepatitis NASH,nash - nonalcoholic Steatohepatitis,non alcoholic steatohepatitis,non-alcoholic steatohepatitis,nonalcoholic Steatohepatitis,nonalcoholic steatohepatitis,Non-alcoholic steatohepatitis
Group 0 name Corresponds to the control (unexposed) group for case-control studies
NAFL (Non-alcoholic fatty liver) patients
Group 1 name Corresponds to the case (exposed) group for case-control studies
NASH (Non-alcoholic steatohepatitis) patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Non-alcoholic fatty liver disease (NAFLD) patients with the presence of hepatic steatosis with necroinflammation and hepatocellular injury with or without fibrosis
Group 0 sample size Number of subjects in the control (unexposed) group
5
Group 1 sample size Number of subjects in the case (exposed) group
8

Lab analysis

Sequencing type
WMS
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified

Statistical Analysis

Alpha Diversity

Pielou Quantifies how equal the community is numerically
increased
Shannon Estimator of species richness and species evenness: more weight on 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 Svetlana up on 2024-7-26

Curated date: 2024/03/15

Curator: Scholastica

Revision editor(s): Scholastica

Source: Fig 4C, Fig 4D

Description: Differential diversity and multiple bacterial species with significantly different abundance found in the intestinal flora of patients with NAFL (Non-alcoholic fatty liver) compared to NASH (Non-alcoholic steatohepatitis)

Abundance in Group 1: increased abundance in NASH (Non-alcoholic steatohepatitis) patients

NCBI Quality ControlLinks
Bacteroides uniformis
Eubacterium ventriosum
Lachnospiraceae bacterium 7_1_58FAA
unclassified Roseburia
unclassified Peptostreptococcaceae

Revision editor(s): Scholastica

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-7-26

Curated date: 2024/03/15

Curator: Scholastica

Revision editor(s): Scholastica

Source: Fig 4C, Fig 4D

Description: Differential diversity and multiple bacterial species with significantly different abundance found in the intestinal flora of patients with NAFL (Non-alcoholic fatty liver) compared to NASH (Non-alcoholic steatohepatitis)

Abundance in Group 1: decreased abundance in NASH (Non-alcoholic steatohepatitis) patients

NCBI Quality ControlLinks
Alistipes

Revision editor(s): Scholastica