๐กThis study aims to comprehensively investigate gut microbiota dysbiosis and metabolite levels in very low or extremely low birth weight (VLBW/ELBW) infants with white matter injury (WMI).
๐Utilizing a multi-omics approach, including 16S rRNA gene sequencing, liquid chromatography-tandem mass spectrometry (LC-MS/MS), and diffusion tension imaging (DTI), the study explores the intricate relationships between gut microbiota, metabolites, and the structural integrity of white matter in the brains of preterm infants.
Methods:
A cohort of 71 preterm infants with gestational age < 32 weeks and weight < 1.5 kg was enrolled in this study. Fecal samples were collected at days zero, 14, and 28 after admission to the intensive care unit. Brain scans via magnetic resonance imaging (MRI) and DTI were conducted at a corrected gestational age of 37โ40 weeks. Based on MRI results, infants were categorized into WMI and non-WMI groups. A multi-omics approach involved 16S rRNA gene sequencing, LC-MS/MS metabolomics, and DTI to identify biomarkers associated with WMI.
Key Findings:
๐ Gut Microbiota Dysbiosis: WMI infants exhibited increased abundance of ๐๐ต๐ข๐ฑ๐ฉ๐บ๐ญ๐ฐ๐ค๐ฐ๐ค๐ค๐ถ๐ด, ๐๐ค๐ช๐ฏ๐ฆ๐ต๐ฐ๐ฃ๐ข๐ค๐ต๐ฆ๐ณ, ๐๐ข๐ค๐ต๐ฆ๐ณ๐ฐ๐ช๐ฅ๐ฆ๐ต๐ฆ๐ด, ๐ข๐ฏ๐ฅ ๐๐ค๐ต๐ช๐ฏ๐ฐ๐ฃ๐ข๐ค๐ต๐ฆ๐ณ๐ช๐ข. Abnormal colonization of ๐๐ต๐ข๐ฑ๐ฉ๐บ๐ญ๐ฐ๐ค๐ฐ๐ค๐ค๐ถ๐ด ๐ข๐ฏ๐ฅ ๐๐ค๐ต๐ช๐ฏ๐ฐ๐ฃ๐ข๐ค๐ต๐ฆ๐ณ๐ช๐ข was observed within the first month of life in WMI infants.
๐ Species-Level Abundance: ๐. ๐ค๐ข๐ฑ๐ณ๐ข๐ฆ was significantly higher in the WMI group, while ๐. ๐ญ๐ฐ๐ฏ๐จ๐ถ๐ฎ was decreased. ๐๐ญ๐ฆ๐ฃ๐ด๐ช๐ฆ๐ญ๐ญ๐ข ๐ข๐ฏ๐ฅ ๐๐ข๐ณ๐ข๐ฃ๐ข๐ค๐ต๐ฆ๐ณ๐ฐ๐ช๐ฅ๐ฆ๐ด were enriched in the meconium of the WMI group, indicating potential early brain damage.
๐ Metabolite Profiling: WMI infants showed significant downregulation in metabolite pathways related to taurine, hypotaurine, arginine biosynthesis, and primary bile acids. Cinobufagin, didesethylflurazepam, N-acetylneuraminic acid, and adenosine 3โ-monophosphate were upregulated, while cholic acid and allocholic acid were downregulated in the WMI group.
๐ Correlation with Brain Structure: ๐. ๐ญ๐ฐ๐ฏ๐จ๐ถ๐ฎ negatively correlated with occipital white matter apparent diffusion coefficient (ADC), suggesting a protective effect. Metabolites like cinobufagin were positively correlated with ADC values, indicating potential brain damage.
๐ This pioneering study unveils severe gut microbiota dysbiosis in VLBW/ELBW infants with WMI, highlighting associations between specific microbial taxa, altered metabolite profiles, and compromised white matter integrity. The findings underscore the potential role of the microbiota-gut-brain axis in the pathogenesis of WMI and open avenues for further research and therapeutic interventions targeting early gut colonization to prevent or mitigate WMI in preterm infants.
Link to the article : https://tinyurl.com/mw2nez7m
