Supplementation of dietary non-digestible oligosaccharides from birth onwards improve social and reduce anxiety-like behaviour in male BALB/c mice
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Objective: The intestinal microbiota is acknowledged to be essential in brain development and behaviour. Their composition can be modulated by prebiotics such as short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharide (lcFOS). Several studies reported potential health benefit of prebiotics on behaviour. As the prebiotic mixture of scGOS and lcFOS is included in infant formula, we investigated the effects of dietary supplementation with this specific mixture from the day of birth onwards on behaviour and intestinal microbiota development in mice.Method: Healthy male BALB/cByJ mice received, from day of birth, a dietary supplement with or without 3% scGOS:lcFOS (9:1). Behavioural tests were performed pre-weaning, in adolescence, early adulthood and adulthood. We assessed faecal microbiota compositions over time, caecal short-chain fatty acids as well as brain mRNA expression of Htr1a, Htr1b and Tph2 and monoamine levels.Results: Compared to control fed mice, scGOS:lcFOS fed mice showed reduced anxiety-like and repetitive behaviour over time and improved social behaviour in adulthood. The serotonergic system in the prefrontal cortex (PFC) and somatosensory cortex (SSC) was affected by the scGOS:lcFOS. In the PFC, mRNA expression of brain-derived neurotrophic factor (Bdnf) was enhanced in scGOS:lcFOS fed mice. Although the bacterial diversity of the intestinal microbiota was unaffected by the scGOS:lcFOS diet, microbiota composition differed between the scGOS:lcFOS and the control fed mice over time. Moreover, an increased saccharolytic and decreased proteolytic fermentation activity were observed in caecum content.Discussion: Supplementing the diet with scGOS:lcFOS from the day of birth is associated with reduced anxiety-like and improved social behaviour during the developmental period and later in life, and modulates the composition and activity of the intestinal microbiota in healthy male BALB/c mice. These data provide further evidence of the potential impact of scGOS:lcFOS on behaviour at several developmental stages throughout life and strengthen the insights in the interplay between the developing intestine and brain.
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Consumption in early life of prebiotics, such as human milk oligosaccharides, supports normal neurodevelopment by altering the microbial richness, composition, and enzymatic activity.
“suggesting that consumption in early life of prebiotics, such as HMOs, supports normal neurodevelopment by altering the microbial richness, composition, and enzymatic activity.”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [268]
Supplementation with oligosaccharides from birth in a mouse model modulated microbiota composition and diversity, increased saccharolytic and decreased proteolytic fermentation while also resulting in improved social and anxiety-like behavior.
“Supplementation with oligosaccharides from birth in a mouse model modulated the microbiota composition and diversity, increased saccharolytic and decreased proteolytic fermentation while also resulting in improved social and anxiety-like behavior (268),”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [268]
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- Authors
- Szklany, K., Wopereis, H., de Waard, C., van Wageningen, T., An, R., van Limpt, K., Knol, J., Garssen, J., Knippels, L. M. J., Belzer, C., & Kraneveld, A. D.
- Affiliations
- Utrecht University (NL)
- Danone (Netherlands) (NL)
- Division of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands
- Wageningen University & Research (NL)
- Department of Gut Biology and Microbiology, Danone Nutricia Research, Utrecht, Netherlands
- Corresponding author
- Kraneveld, Aletta D.
- ORCID
- Venue
- Nutritional Neuroscience
- Publisher
- Informa UK Limited
- Published
- 2019-03-14
- Volume
- 23
- Issue
- 11
- Pages
- 896-910
- ISSN
- 1028-415X (ISSN-L)
- 1476-8305
- OpenAlex
- W2922136224
- Cited by
- 46
- References
- 60
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 3 · 2023: 9 · 2022: 6 · 2021: 8 · 2020: 5 · 2019: 2
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nutritional Neuroscience (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Socio-Environmental Systems Modeling (acceptedVersion, cc-by-nc-nd)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by-nc-nd)
- Funders
- Utrecht University
- Nutricia Research
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Microbial Metabolites in Food Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
- Keywords
- prebiotics, dietary supplementation, anxiety-like behavior, social behavior, repetitive behavior, gut microbiota, gut-brain axis, serotonergic system, 5-HT1A receptor, 5-HT1B receptor, tryptophan hydroxylase 2, brain-derived neurotrophic factor, short-chain fatty acids, caecal fermentation, brain development, infant formula, BALB/c mice
- MeSH terms
- Gastrointestinal Microbiome, Animals, Anxiety, Behavior, Animal, Brain, Male, Mice, Inbred BALB C, Oligosaccharides, Social Behavior, Vocalization, Animal, Biogenic Monoamines, Prebiotics
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