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Fecal microbiome profiles in infants with biliary atresia versus nonbiliary atresia cholestasis: a pilot study
Nur Azizah1, Fadilah Fadilah2,3, Silvia Werdhy Lestari4
1Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Insights
Infant cholestasis, including biliary atresia (BA), shows distinct gut microbiome differences. Biliary atresia and non-BA cholestasis exhibit specific bacterial genus enrichments, impacting liver function and requiring targeted treatments.
Area of Science:
- Microbiology
- Pediatric Gastroenterology
- Hepatology
Background:
- Cholestasis, a condition of disrupted bile flow, can cause severe liver disease in newborns, with biliary atresia (BA) being a frequent cause.
- The gut microbiome significantly influences liver injury in both BA and non-BA cholestasis.
- Limited data exists on the specific gut microbiome composition differences between BA and non-BA cholestasis.
Purpose of the Study:
- To investigate and compare the gut microbiome profiles of infants with BA, non-BA cholestasis, and healthy controls.
- To identify differences in microbial composition associated with cholestatic liver disease in infants.
- To analyze the gut microbiome in an Indonesian pediatric population.
Main Methods:
- Fecal samples were collected from 12 infants with BA, 8 with non-BA cholestasis, and 8 healthy controls (HCs).
- 16S rRNA amplicon sequencing was performed on fecal DNA to analyze microbial composition.
- Microbial alterations were correlated with liver function indicators.
Main Results:
- The BA group showed increased Proteobacteria and decreased Firmicutes compared to non-BA cholestasis.
- Specific genera like Bacteroides and Dialister were enriched in BA, while Klebsiella and Pseudomonas were enriched in non-BA cholestasis.
- Healthy controls had higher enrichment of genera such as Parabacteroides and Clostridium innocuum group. Cytomegalovirus detection correlated with microbial shifts and altered diversity.
Conclusions:
- Infants with BA and non-BA cholestasis exhibit distinct gut microbiome genus enrichments.
- These microbial differences underscore the need for targeted therapeutic strategies to mitigate liver injury progression in cholestatic infants.
- Understanding these specific microbial profiles is crucial for developing novel treatment approaches.
Background:
Cholestasis is characterized by disrupted bile flow and can lead to severe liver disease in newborns, of which biliary atresia (BA) is a common cause. The gut microbiome plays a crucial role in aggravating liver injury in BA and non-BA cholestasis. However, information is lacking regarding the differences in gut microbiome composition between patients with BA and non-BA cholestasis.
Purpose:
This study aimed to assess the gut microbiome profile of infants with BA versus those with non-BA cholestasis and healthy controls in an Indonesian population.
Methods:
We investigated the changes in the microbial composition of fecal samples from 12 infants with BA and 8 with non-BA cholestasis and compared them with those of 8 age-matched healthy controls (HCs). Fecal DNA from all the participants was subjected to 16S rRNA amplicon sequencing.
Results:
The fecal microbiome at the phylum level differed between the BA and non-BA cholestasis groups with increased Proteobacteria and decreased Firmicutes. At the genus level, the BA group was enriched with Bacteroides, unclassified Enterobacteriaceae, and Dialister (P<0.05), whereas the non-BA group was enriched with Klebsiella, Chryseobacterium, Acinetobacter, and Pseudomonas (P<0.05). Parabacteroides, unclassified Lachnospiraceae, Actinomyces, Anaerococcus, Clostridium innocuum group, Collinsella, Gemella, and Peptostreptococcaceae (P<0.05) were more enriched in the HC than in the other 2 groups. Detected cytomegalovirus in fecal samples was associated with significant microbial shifts, including increased Lactobacillus, decreased Escherichia-Shigella, and altered Faith's phylogenetic diversity, highlighting its potential role in gut microbiome modulation. Microbial alterations in patients with BA versus non-BA cholestasis were significantly correlated with liver function indicators.
Conclusion:
The BA and non-BA groups showed specific genus enrichment, highlighting the urgent need to identify potential treatments to inhibit the progression of liver injury in infants with cholestasis.
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