Faecal transplantation from exuberant toddlers increases exploratory behaviour in rats

Aatsinki, A.-K.; Collins, J. M.; Munukka, E.; Nolvi, S.; Kara, N.; Wilmes, L.; Deady, C.; Salin, I.; Eskola, E.; Huovinen, V.; Lahtela, H.; Bridgett, D.; Korja, R.; Keskitalo, A.; Isokaanta, H.; Dickens, A. M.; Santosh, L.; Kallonen, T.; Bayal, N.; Mykkanen, J.; Parnanen, K.; Perasto, L.; Lahti, L.; Clarke, G.; Cryan, J. F.; Dinan, T. G.; Karlsson, H.; O'Mahony, S. M.; Karlsson, L.

doi:10.1101/2025.10.10.681629

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bioRxiv · 10.1101/2025.10.10.681629

Faecal transplantation from exuberant toddlers increases exploratory behaviour in rats

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Abstract

BackgroundBehavioural phenotypes have previously been transferred via faecal microbiota transplantation (FMT) from patients with psychiatric disorders to rodents. Studies indicate that the gut microbiota composition may be linked to certain temperament traits, defined as biologically-based differences in emotional reactivity and self-regulation. Here, we aimed to determine if the gut microbiota plays a role in temperament using an FMT approach. We focused on the temperament traits of exuberance, defined as positive reactivity, decreased behavioural inhibition, and high behavioural approach tendencies. MethodsFaeces from 2.5-year-old toddlers from FinnBrain Birth Cohort Study with high exuberance/approach or high behavioural inhibition in the LabTAB bubbles-episode was transferred to juvenile male Sprague Dawley rats (age 22/23 days). Behaviour of the rat recipients (n=53) was assessed using the novel non-social arena, novel social arena, hole board test for exploratory behaviour, social approach-avoidance test, and forced swim test. The faecal pellets collected from the rodents were analyzed with 16s rRNA sequencing and faecal samples from the sample of toddlers (which included the donors, n=176) were analysed using short-read metagenomic sequencing. The striatum and prefrontal cortex from the rodents brains were analysed post-mortem using RNAseq. ResultsMicrobiome from toddlers with high exuberance traits induced increased exploratory behaviour compared to vehicle-controls and rats receiving faeces from inhibited toddlers. Locomotor activity, social, and depressive-like behaviour remained unaffected. We noted a downregulation of the dopamine synapse pathway within the striatum of the rats that received faeces from the inhibited trait donors compared with vehicle-controls. Faecal microbiota of rats receiving faeces from the same donor resembled more each other than rats from a different cage. Clostridium species AM29 11AC in toddler microbiome was positively related to exuberance, but there were no cross-sectional associations between faecal metabolites in the human sample. ConclusionsFMT from exuberant toddlers lead to altered exploratory-related behaviour in rats.

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Aatsinki, A.-K., Collins, J. M., Munukka, E., Nolvi, S., Kara, N., Wilmes, L., Deady, C., Salin, I., Eskola, E., Huovinen, V., Lahtela, H., Bridgett, D., Korja, R., Keskitalo, A., Isokaanta, H., Dickens, A. M., Santosh, L., Kallonen, T., Bayal, N., Mykkanen, J., Parnanen, K., Perasto, L., Lahti, L., Clarke, G., Cryan, J. F., Dinan, T. G., Karlsson, H., O'Mahony, S. M., Karlsson, L.. 2025-10-11. Faecal transplantation from exuberant toddlers increases exploratory behaviour in rats. https://doi.org/10.1101/2025.10.10.681629

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