Abstract
BACKGROUND: There are two subtypes of infantile cholestasis (IC): high-γ-glutamyltransferase (GGT) and low-GGT (LG) cholestasis. This study aims to investigate the differences in the gut microbiota between infants with cholestasis and healthy infants and the correlations between the gut microbiota and blood or urine metabolites associated with high-GGT (HG) and LG IC subtypes. METHODS: A total of 37 infants were recruited into the cholestasis (Cho) group, including 21 infants with HG and 16 infants with LG levels, with 23 infants included in the control (Con) group. The gut microbiota composition was comprehensively analyzed, as were blood and urine metabolites, clinical indicators, and their correlations. The study was registered in both the Chinese Clinical Trial Registry (www.chictr.org.cn, ChiCTR2300072387) and the National Medical Research Registration & Filing Information System (www.medicalresearch.org.cn, MR-35-24-056613). RESULTS: The Lactobacillus, Streptococcus, Bacteroides, and Lactococcus abundances were greater and the Lachnoclostridium abundance was lower in the Cho group than in the Con group. The Bacteroides abundance was significantly greater in the HG group than in the LG group. The characteristic bacterial taxa in the HG group were Bacteroides, Lactococcus, Streptococcus thermophilus TH1435, Haemophilus, Parabacteroides and Subgroup_6, whereas those in the LG group were Gammaproteobacteria, Streptococcus, Blautia, Pasteurellaceae, Staphylococcus, Megamonas, Helicobacter and Bacillus. The HG group presented higher concentrations of alkapton-3 and lower concentrations of methylfumaric acid-2, 2-hydroxyglutaric acid-3 and malic acid-3 than the LG group. The abundances of Pasteurellaceae and Parabacteroides were negatively correlated with GGT levels and pediatric end-stage liver disease (PELD) scores, respectively. CONCLUSIONS: Infants with cholestasis exhibit gut microbiota dysbiosis. Notably, distinct differences in the microbiota profiles were observed between the HG and LG cholestasis groups. Bacteroides and Parabacteroides may play roles in the HG group, whereas Gammaproteobacteria and Pasteurellaceae did so in the LG group. Our research provides new insights into the relationships between gut microbiota and different subtypes of IC, but the causal relationships and specific mechanisms need to be characterized further and verified.