Alterations of Gut Microbiota in Cholestatic Infants and Their Correlation With Hepatic Function

Study information

Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

30483228

DOI Digital object identifier for electronic documents.

10.3389/fmicb.2018.02682

URI

Authors

Guo C, Li Y, Wang P, Li Y, Qiu C, Li M, Wang D, Zhao R, Li D, Wang Y, Li S, Dai W, Zhang L

Journal

Frontiers in microbiology

Year

2018

Keywords:

16S rRNA, bacterial biomarkers, co-abundance network, hepatic function, infantile cholestasis

Cholestasis is a major hepatic disease in infants, with increasing morbidity in recent years. Accumulating evidence has revealed that the gut microbiota (GM) is associated with liver diseases, such as non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. However, GM alterations in cholestatic infants and the correlation between the GM and hepatic functions remain uninvestigated. In this study, 43 cholestatic infants (IC group) and 37 healthy infants (H group) were enrolled to detect GM discrepancies using 16S rDNA analysis. The diversity in the bacterial community was significantly lower in the IC group than that in the H group (P = 0.013). After determining the top 10 abundant genera of microbes in the IC and H groups, we found that 13 of them were differentially enriched, including Bifidobacterium, Bacteroides, Streptococcus, Enterococcus, and Staphylococcus. As compared with the H group, the IC group had a more complex GM co-occurrence network featured by three core nodes: Phyllobacterium, Ruminococcus, and Anaerostipes. In addition, the positive correlation between Faecalibacterium and Erysipelatoclostridium (r = 0.689, P = 0.000, FDR = 0.009) was not observed in the IC patients. Using the GM composition, the cholestatic patients can be distinguished from healthy infants with high accuracy [areas under receiver operating curve (AUC) > 0.97], wherein Rothia, Eggerthella, Phyllobacterium, and Blautia are identified as valuable biomarkers. Using KEGG annotation, we identified 32 functional categories with significant difference in enrichment of the GM of IC patients, including IC-enriched functional categories that were related to lipid metabolism, biodegradation and metabolism of xenobiotics, and various diseases. In contrast, the number of functions associated with amino acid metabolism, nucleotide metabolism, and vitamins metabolism was reduced in the IC patients. We also identified significant correlation between GM composition and indicators of hepatic function. Megasphaera positively correlated with total bilirubin (r = 0.455, P = 0.002) and direct bilirubin (r = 0.441, P = 0.003), whereas γ-glutamyl transpeptidase was positively associated with Parasutterella (r = 0.466, P = 0.002) and negatively related to Streptococcus (r = -0.450, P = 0.003). This study describes the GM characteristics in the cholestatic infants, illustrates the association between the GM components and the hepatic function, and provides a solid theoretical basis for GM intervention for the treatment of infantile cholestasis.

Experiment 1

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Victoria

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: Extrahepatic cholestasis cholestasis of extrahepatic bile duct,Cholestasis, Extrahepatic,extrahepatic bile duct cholestasis,extrahepatic biliary Stasis,extrahepatic biliary stasis,extrahepatic cholestasis,extrahepatic cholestasis (finding),extrahepatic obstructive biliary disease,extrahepatic obstructive biliary disease (disorder),Extrahepatic cholestasis

Group 0 name Corresponds to the control (unexposed) group for case-control studies: healthy infants

Group 1 name Corresponds to the case (exposed) group for case-control studies: cholestasis infants

Group 0 sample size Number of subjects in the control (unexposed) group: 37

Group 1 sample size Number of subjects in the case (exposed) group: 43

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 4 weeks

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: Mann-Whitney (Wilcoxon)

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

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased

Signature 1

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Christina Brown

Revision editor(s): WikiWorks

Source: Figure 2+ text

Description: Differentially abundundant gut microbiota in cholestatic infants vs healthy infants

Abundance in Group 1: increased abundance in cholestasis infants

NCBI	Quality Control	Links
Streptococcus
Enterococcus
Staphylococcus
Megasphaera
Phyllobacterium
Megamonas

Revision editor(s): WikiWorks

Signature 2

Edit History Delete

Flag for review

Your review change was submitted

Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Christina Brown

Revision editor(s): WikiWorks

Source: Figure 2 + text

Description: Differentially abundundant gut microbiota in cholestatic infants vs healthy infants

Abundance in Group 1: decreased abundance in cholestasis infants

NCBI	Quality Control	Links
Bifidobacterium
Bacteroides
Blautia
Faecalibacterium
Roseburia
Anaerostipes
Collinsella

Revision editor(s): WikiWorks