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. 2023 Nov 18;23(1):357.
doi: 10.1186/s12866-023-03115-1.

Alterations in gut microbiota and metabolite profiles in patients with infantile cholestasis

Meng Jin #  1 , Jinghua Cui #  2 , Huijuan Ning  1 , Meijuan Wang  1 , Wenwen Liu  1 , Kunyu Yao  1 , Jing Yuan  3 , Xuemei Zhong  4
Affiliations

Alterations in gut microbiota and metabolite profiles in patients with infantile cholestasis

Meng Jin et al. BMC Microbiol. .

Abstract

Background: Infantile cholestasis (IC) is the most common hepatobiliary disease in infants, resulting in elevated direct bilirubin levels. Indeed, hepatointestinal circulation impacts bile acid and bilirubin metabolism. This study evaluates changes in the gut microbiota composition in children with IC and identifies abnormal metabolite profiles associated with microbial alterations.

Results: The gut microbiota in the IC group exhibits the higher abundance of Veillonella, Streptococcus and Clostridium spp. (P < 0.05), compared to healthy infants (CON) group. Moreover, the abundance of Ruminococcus, Vibrio butyricum, Eubacterium coprostanogenes group, Intestinibacter, and Faecalibacterium were lower (P < 0.05). In terms of microbiota-derived metabolites, the levels of fatty acids (palmitoleic, α-linolenic, arachidonic, and linoleic) (P < 0.05) increased and the levels of amino acids decreased in IC group. Furthermore, the abundances of Ruminococcus, Eubacterium coprostanoligenes group, Intestinibacter and Butyrivibrio are positively correlated with proline, asparagine and aspartic acid, but negatively correlated with the α-linolenic acid, linoleic acid, palmitoleic acid and arachidonic acid. For analysis of the relationship between the microbiota and clinical index, it was found that the abundance of Veillonella and Streptococcus was positively correlated with serum bile acid content (P < 0.05), while APTT, PT and INR were negatively correlated with Faecalibalum and Ruminococcus (P < 0.05).

Conclusion: Microbiota dysbiosis happened in IC children, which also can lead to the abnormal metabolism, thus obstructing the absorption of enteral nutrition and aggravating liver cell damage. Veillonella, Ruminococcus and Butyrivibrio may be important microbiome related with IC and need further research.

Keywords: Butyrivibrio; Gut microbiota; Infantile cholestasis (IC); Microbiota-derived metabolites; Ruminococcus; Veillonella.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Characteristics of gut microbiota in infantile cholestasis (IC; n = 20) and control (CON; n = 20) groups. A. Distribution of gut microbiota at the phylum level in 40 specimens; B. distribution of gut microbiota at the genus level in 40 samples; C. score plot of differential species showing linear discriminant analysis of differentially abundant genera between the two groups; D. annotated cladogram of differential species showing statistically significant taxa between the two groups; 1E. relative abundance histogram. Solid line represents the mean relative abundance, dashed line represents the median relative abundance; F. distribution of gut microbiota with significant differences in relative abundance between the two groups; G. Heatmap of KEGG pathway enrichment analysis
Fig. 2
Fig. 2
Profiling of gut microbiota-derived metabolites in the infantile cholestasis (IC) and control (CON) groups. A Categorical and quantitative distribution of metabolites across all samples; B. Distribution of metabolites in different groups; C. univariate statistical analysis of differential metabolites. Red dots on the right: upregulated metabolites in the IC compared to CON group, blue dots on the left: downregulated metabolites, gray dots (NONE): metabolites that did not meet the threshold requirements; D. multivariate statistical analysis of differential metabolites; x-axis: Pearson's correlation coefficients between each metabolite and first principal component (P1), y-axis: contribution of metabolites to the model discrimination (variable importance in projection; VIP). Green dots: metabolites with VIP score > 1; 2E. box plot showing the top nine differential metabolites
Fig. 3
Fig. 3
Metabolic pathway enrichment analysis of fecal samples in healthy infants and infants with infantile cholestasis(IC). A Pathway enrichment analysis for predicted metabolite sets; colors and length of horizontal bars represent the P-values of pathway enrichment and fold enrichment, respectively; 3. bubble map of metabolic pathway enrichment analysis
Fig. 4
Fig. 4
Correlation of gut microbiota, metabolites, and clinical indicators in healthy infants (CON) and infants with infantile cholestasis (IC). Red boxes: positive correlation, blue boxes: negative correlation (*P < 0.05; **P < 0.01). A Relationship between differential bacterial genera and differential metabolites in the two groups; B Relationship between differential bacterial genera and clinical indicators in the two groups
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