PreprintCited by 4Gut microbiota and healthInfant Nutrition and HealthMetabolomics and Mass Spectrometry Studies

Dynamics of Gut Metabolome and Microbiome Maturation during Early Life

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Aatsinki, Anna-Katariina, Lamichhane, Santosh, Isokääntä, Heidi, Sen, Partho, Kråkström, Matilda, Alves, Marina Amaral, Keskitalo, Anniina, Munukka, Eveliina +8 more·2023·medRxiv

Abstract

Early-life gut microbiome-metabolome crosstalk has a pivotal role in the maintenance of host physiology. However, our understanding on early-life gut microbiome-metabolome maturation trajectories in humans remains limited. This study aims to explore the longitudinal patterns of gut metabolites during early life, and how they are related to gut microbiota composition in birth cohort samples of n = 670 children collected at 2.5 (n=272), 6 (n=232), 14 (n=289), and 30 months (n=157) of age. Factor analysis showed that breastfeeding has an effect on several metabolites including secondary bile acids. We found that the prevalent gut microbial abundances were associated with metabolite levels, especially in the 2.5 months-olds. We also demonstrated that the prevalent early colonizers Bacteroides, Escherichia and Bifidobacterium abundances associated with microbial metabolites bile acids especially in the breastfed infants. Taken together, our results suggests that as the microbiome matures during the early-life there is an association with the metabolome composition in an analogous fashion to how the genome information mature during early life.

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Registry

Crossref · 10.1101/2023.05.29.23290441

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  • Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes.

    “Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes1–6; however, the bacterial gene(s) responsible for their production remain unknown.”

    From Bile Acids Are Substrates for Amine N-Acyl Transferase Activity by Bile Salt Hydrolase (2022) · cites this paper as [6]

    The Introduction (page unavailable) says microbial transformation of bile acids can regulate human physiology, and the Discussion (page unavailable) links bile acids to metabolic processes. Neither passage says gut bacteria produce amino acid bile acid amidates specifically; the Discussion instead describes bacterial deconjugation of glycine from bile acids. (LLM, conf=0.84)

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  • The bacterial enzymes responsible for producing amino acid bile acid amidates are unknown.

    “The enzymes responsible for these conjugation reactions are unknown.”

    From Bile Acids Are Substrates for Amine N-Acyl Transferase Activity by Bile Salt Hydrolase (2022) · cites this paper as [6]

    The Discussion (page unavailable) describes bile salt hydrolase enzymes that deconjugate bile acids, not enzymes that produce amino acid bile acid amidates. Searches for the claimed unknown conjugation enzymes and for amino acid bile acid amidates found no passage in our copy addressing whether those enzymes are known. (LLM, conf=0.75)

    Experimental — accuracy not yet measured
  • Recent studies demonstrated that bacteria have bile acid amine N-acyltransferase activity, with dozens of bacterially conjugated amino acid amidates identified.

    “Recent studies demonstrated that bacteria, in addition to the host, have bile acid amine N-acyltransferase activity, with dozens of bacterially conjugated amino acid amidates identified1–4,6,17.”

    From Bile Acids Are Substrates for Amine N-Acyl Transferase Activity by Bile Salt Hydrolase (2022) · cites this paper as [6]

    The Discussion describes bacterial bile acid metabolism, particularly bile salt hydrolase activity and deconjugation, but does not address bacterial bile acid amine N-acyltransferase activity. A search for bacterial conjugation and amino acid amidates found no passage reporting the identification of dozens of such compounds. The supplied passages have no page numbers. (LLM, conf=0.74)

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Authors
Aatsinki, A.-K., Lamichhane, S., Isokääntä, H., Sen, P., Kråkström, M., Alves, M. A., Keskitalo, A., Munukka, E., Karlsson, H., Perasto, L., Lukkarinen, M., Oresic, M., Kailanto, H.-M., Karlsson, L., Lahti, L., & Dickens, A. M.
Affiliations
  • University of Turku (FI)
  • Åbo Akademi University (FI)
  • Universidade Federal do Rio de Janeiro (BR)
  • Turku University Hospital (FI)
Corresponding author
  • Aatsinki, Anna-Katariina
  • Dickens, Alex M
Venue
medRxiv
Publisher
openRxiv
Published
2023-05-30
OpenAlex
W4378834673
Cited by
4
References
44
Citations by year
2026: 1 · 2025: 1 · 2024: 2
Type
posted content
Language
en
Open access
Licence
cc-by
Locations
medRxiv (acceptedVersion, cc-by)
Funders
  • Yrjö Jahnssonin Säätiö (P3654)
  • Jalmari ja Rauha Ahokkaan Säätiö
  • Finska Läkaresällskapet
  • Waterloo Foundation
  • European Commission (101094099)
  • Academy of Finland (347924, #308176, 295741, #325292, #253270, 134950, 347640)
  • Jane ja Aatos Erkon Säätiö
  • Juho Vainion Säätiö (295741)
  • Signe ja Ane Gyllenbergin Säätiö
  • Emil Aaltosen Säätiö
  • Suomalainen Lääkäriseura Duodecim
  • Instrumentariumin Tiedesäätiö
  • Turun Yliopistollinen Keskussairaala
  • HORIZON EUROPE Framework Programme (101094099)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
Keywords
gut microbiota, gut metabolome, early life, breastfeeding, secondary bile acids, Bacteroides, Escherichia, Bifidobacterium, infant gut microbiota, birth cohort

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