Dynamics of gut metabolome and microbiota maturation during early life

Anna Katariina Aatsinki; Santosh Lamichhane; Heidi Isokääntä; Partho Sen; Matilda Kråkström; Marina Amaral Alves; Anniina Keskitalo; Eveliina Munukka; Hasse Karlsson; Laura Perasto; Minna Lukkarinen; Matej Oresic; Henna Maria Kailanto; Linnea Karlsson; Leo Lahti; Alex M. Dickens

doi:10.1016/j.isci.2025.113596

Dynamics of gut metabolome and microbiota maturation during early life

Anna Katariina Aatsinki
, Santosh Lamichhane
, Heidi Isokääntä
, Partho Sen
, Matilda Kråkström
, Marina Amaral Alves
, Anniina Keskitalo
, Eveliina Munukka
, Hasse Karlsson
, Laura Perasto
, Minna Lukkarinen
, Matej Oresic
, Henna Maria Kailanto
, Linnea Karlsson
, Leo Lahti
, Alex M. Dickens^*

^*Corresponding author for this work

Turku Bioscience Centre

Research output: Contribution to journal › Article › Scientific › peer-review

Abstract

Early-life gut microbiome-metabolome crosstalk plays a crucial role in maintaining host physiology. The microbially produced metabolites often convey effects on host health and physiology. This study investigates the gut metabolites, including short-chain fatty acids (SCFAs), bile acids (BAs), and polar metabolites, and their relationship to gut microbiota composition in a birth cohort of 670 children. Samples were collected at 2.5 (n = 272), 6 (n = 232), 14 (n = 289), and 30 months (n = 157) of age. We identified the trajectories of the fecal metabolome that relate to the maturation of the early-life gut microbiota. We found that prevalent gut microbial abundances were associated with microbial metabolite levels, particularly in 2.5-month-old infants. Here, the abundances of early colonizers, e.g., Bacteroides, Escherichia, and Bifidobacterium, were associated with microbial metabolites, especially secondary BAs, particularly in breastfed infants. Our results suggest that early-life gut microbiota associates with changes in metabolome composition, particularly BAs, which may have physiological implications.

Original language	English
Article number	113596
Journal	iScience
Volume	28
Issue number	11
DOIs	https://doi.org/10.1016/j.isci.2025.113596
Publication status	Published - 21 Nov 2025
MoE publication type	A1 Journal article-refereed

Funding

Finnbrain Birth cohort Study (H.K.) has been funded by the Research Council of Finland (grant numbers 253270 , 134950 ), Jane and Aatos Erkko Foundation , as well as Signe and Ane Gyllenberg Foundation . L.K. was funded by the Research Council of Finland (grant numbers 308176 and 325292 ), Yrjö Jahnsson Foundation ( 6847 , 6976 ), Signe and Ane Gyllenberg Foundation , Finnish State Grants for Clinical Research ( P3654 ), Jalmari and Rauha Ahokas Foundation , and Waterloo Foundation ( 2110-3601 ). A.K.A. was supported by Yrjö Jahnsson Foundation , Psychiatry Research Foundation , Emil Aaltonen Foundation , Brain Foundation , Instrumentarium Science Foundation , Signe and Ane Gyllenberg Foundation , Duodecim Finnish Medical Society , Juho Vainio Foundation , and Research Council of Finland (grant number 347640 ). H.I. had a grant from Finnish Cultural Foundation [no 00230482 ]. L.L. was supported by the Research Council of Finland (grant number 330887 ). E.M. was supported by the government research grant awarded to Turku University Hospital . A.D. has been funded by the Waterloo Foundation and the Research Council of Finland ( 347924 ). “Inflammation in human early life: targeting impacts on life-course health” (INITIALISE) consortium funded by the Horizon Europe Program of the European Union under Grant Agreement 101094099 (to M.O., H.K., A.D.). We want to thank all the participating families and the FinnBrain staff and assisting personnel. Turku Metabolomics Center and Biocenter Finland is acknowledged for the collaboration regarding fecal sample metabolomics. This work was supported by the “Inflammation in human early life: targeting impacts on life-course health” (INITIALISE) consortium funded by the Horizon Europe Program of the European Union under Grant Agreement 101094099.Finnbrain Birth cohort Study (H.K.) has been funded by the Research Council of Finland (grant numbers 253270, 134950), Jane and Aatos Erkko Foundation, as well as Signe and Ane Gyllenberg Foundation. L.K. was funded by the Research Council of Finland (grant numbers 308176 and 325292), Yrjö Jahnsson Foundation (6847, 6976), Signe and Ane Gyllenberg Foundation, Finnish State Grants for Clinical Research (P3654), Jalmari and Rauha Ahokas Foundation, and Waterloo Foundation (2110-3601). A.K.A. was supported by Yrjö Jahnsson Foundation, Psychiatry Research Foundation, Emil Aaltonen Foundation, Brain Foundation, Instrumentarium Science Foundation, Signe and Ane Gyllenberg Foundation, Duodecim Finnish Medical Society, Juho Vainio Foundation, and Research Council of Finland (grant number 347640). H.I. had a grant from Finnish Cultural Foundation [no 00230482]. L.L. was supported by the Research Council of Finland (grant number 330887). E.M. was supported by the government research grant awarded to Turku University Hospital. A.D. has been funded by the Waterloo Foundation and the Research Council of Finland (347924). “Inflammation in human early life: targeting impacts on life-course health” (INITIALISE) consortium funded by the Horizon Europe Program of the European Union under Grant Agreement 101094099 (to M.O., H.K., A.D.).

Keywords

Gastroenterology
Metabolomics
Microbiology
Microbiome
Omics
Pediatrics

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10.1016/j.isci.2025.113596Licence: CC BY

PIIS2589004225018577Final published version, 8.83 MBLicence: CC BY

https://urn.fi/URN:NBN:fi-fe202601279149

Cite this

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. (2025). Dynamics of gut metabolome and microbiota maturation during early life. iScience, 28(11), Article 113596. https://doi.org/10.1016/j.isci.2025.113596

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AU - Kråkström, Matilda

AU - Alves, Marina Amaral

AU - Keskitalo, Anniina

AU - Munukka, Eveliina

AU - Karlsson, Hasse

AU - Perasto, Laura

AU - Lukkarinen, Minna

AU - Oresic, Matej

AU - Kailanto, Henna Maria

AU - Karlsson, Linnea

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AU - Dickens, Alex M.

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Dynamics of gut metabolome and microbiota maturation during early life

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Keywords

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