Abstract
The gut microbiome is associated with pathological neurophysiological evolvement in extremely premature infants suffering from brain injury. The exact underlying mechanism and its associated metabolic signatures in infants are not fully understood. To decipher metabolite profiles linked to neonatal brain injury, we investigate the fecal and plasma metabolome of samples obtained from a cohort of 51 extremely premature infants at several time points, using liquid chromatography (LC)-high-resolution mass spectrometry (MS)-based untargeted metabolomics and LC-MS/MS-based targeted analysis for investigating bile acids and amidated bile acid conjugates. The data are integrated with 16S rRNA gene amplicon gut microbiome profiles as well as patient cytokine, growth factor, and T cell profiles. We find an early onset of differentiation in neuroactive metabolites between infants with and without brain injury. We detect several bacterially derived bile acid amino acid conjugates in plasma and feces. These results provide insights into the early-life metabolome of extremely premature infants.
| Original language | English |
|---|---|
| Article number | 101480 |
| Number of pages | 24 |
| Journal | Cell Reports Medicine |
| Volume | 5 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 16 Apr 2024 |
Funding
We thank all families for their participation and all medical staff for their help with sample collection. The Mass Spectrometry Center of the Faculty of Chemistry at the University of Vienna is acknowledged for technical support, and the colleagues at the University of Vienna and the Medical University of Vienna are thanked for critical feedback and discussion. This project was funded by an inter-university cluster project grant between the University of Vienna and the Medical University of Vienna (“PreMi-BraIn”) and co-funding by the European Union ( ERC , FunKeyGut 741623 to D.B. and EXPOMET 101043321 to B.W.). Views and opinions expressed are those of the authors only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. We thank all families for their participation and all medical staff for their help with sample collection. The Mass Spectrometry Center of the Faculty of Chemistry at the University of Vienna is acknowledged for technical support, and the colleagues at the University of Vienna and the Medical University of Vienna are thanked for critical feedback and discussion. This project was funded by an inter-university cluster project grant between the University of Vienna and the Medical University of Vienna (“PreMi-BraIn”) and co-funding by the European Union (ERC, FunKeyGut 741623 to D.B. and EXPOMET 101043321 to B.W.). Views and opinions expressed are those of the authors only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. Conceptualization, B.W. L.W. D.B. and M.P.; methodology, M.P. D.W. D.S. and B.W.; investigation, M.P.; visualization, M.P.; funding acquisition, B.W. L.W. and D.B.; project administration, B.W. L.W. and D.B.; supervision, B.W. L.W. and D.B.; writing – original draft, M.P. and B.W.; writing – review & editing, M.P. B.W. L.W. D.B. D.W. D.S. A.B. and K.K.-S. The authors declare no competing interests.
Austrian Fields of Science 2012
- 106026 Ecosystem research
- 106022 Microbiology
- 106059 Microbiome research
Keywords
- bile acid amino acid conjugates
- extremely premature infant
- gut-immune-brain axis
- neonatal brain injury
- untargeted metabolomics