Key bacterial taxa determine longitudinal dynamics of aromatic amino acid catabolism in infants’ gut

ABSTRACT

The development of the gut microbiota in early life is linked to metabolic, neuronal, and immunological development. Recent studies have shown that bacterial production of short-chain fatty acids (SCFAs) and aromatic amino acid (AAA) catabolites in the gut can mediate host–microbe interactions. However, the dynamics of these microbiota-derived metabolites and the key bacterial taxa producing AAA catabolites during infancy are largely unknown. Here, we investigated the longitudinal dynamics of the microbiota and microbiota-derived SCFAs and AAA catabolites in more than 200 fecal samples from 25 healthy breast- or mixed-fed Danish infants during the first 6 months of life. We found that the gut microbiota composition and metabolism were highly individual but showed significant development over time. SCFAs and specific groups of AAA catabolites showed distinct temporal abundance patterns. Furthermore, we identified bacterial taxa responsible for the generation of AAA catabolites by associating the dynamics of gut microbial taxa and AAA catabolites and subsequently validating these associations in vitro by cultivation of strains representing the associated taxa. In addition to specific Bifidobacterium species being the main producers of aromatic lactic acids, we identified Peptostreptococcus anaerobius as the main producer of aromatic propionic acids, Ruminococcus gnavus as a main producer of tryptamine, and Enterococcus species as main tyramine producers in infants’ gut. Thus, our results showcase the temporal dynamics of key gut microbial metabolites in early life and demonstrate that the appearance and abundance of specific AAA catabolites result from the appearance and abundance of specific key bacterial taxa in infants’ gut.

KEYWORDS:

• Infant
• gut microbiota
• metabolites
• short chain fatty acids
• aromatic amino acid catabolites
• longitudinal sampling

Acknowledgments

We thank the children and families participating in the CIG cohort and Aarstiderne A/S for providing a small gift for the CIG participants. We thank Marlene Danner Dalgaard at the Technical University of Denmark in-house facility (DTU Multi-Assay Core, DMAC) for performing the 16S rRNA amplicon sequencing and MS-Omics ApS (Vedbæk, Denmark) for performing the short-chain fatty analyses.

Author Contributions

H.M.R. and M.F.L conceived and designed the experiments. M.F.L prepared the samples for sequencing/qPCR and analyzed the sequencing/qPCR data. H.M.R prepared the samples for fecal metabolome analyses and performed the targeted metabolomics experiments. A.K.S. performed in vitro fermentations. A.K.S prepared and did targeted metabolomics for in vitro samples for semi-quantification of AAA metabolites together with M.P. All authors wrote and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data Availability Statement

16S rRNA gene amplicon sequencing data has been deposited in the Sequence Read Archive (SRA) under BioProject PRJNA554596 (CIG).

Supplementary Material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2221426

Additional information

Funding

This work was supported by Augustinus Fonden (grant no. 17-2003 to H.M.R.), Hørslev Fonden (grant no. 203866 to H.M.R.), Beckett Fonden (grant no. 17-2-0551 to H.M.R.), Ejnar og Aase Danielsens Fond (grant no. 10-002019 to H.M.R.), the Independent Research Fund Denmark (MOTILITY; grant no. 0171-00006B to H.M.R.), and the Novo Nordic Foundation (PRIMA; grant no. NNF19OC0056246).