- Title
- Neonatal immune challenge influences the microbiota and behaviour in a sexually dimorphic manner
- Creator
- Cuskelly, A.; Hoedt, E. C.; Harms, L.; Talley, N. J.; Tadros, M. A.; Keely, S.; Hodgson, D. M.
- Relation
- Brain, Behavior, and Immunity Vol. 103, p. 232-242
- Publisher Link
- http://dx.doi.org/10.1016/j.bbi.2022.04.023
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2022
- Description
- There is comorbidity between anxiety disorders and gastrointestinal disorders, with both linked to adverse early life events. The microbiome gut-brain-axis, a bidirectional communication system, is plastic throughout the neonatal period and is a possible mediator of this relationship. Here, we used a well-established neonatal rodent immune activation model to investigate the long-term effect of neonatal lipopolysaccharide (LPS) exposure on adult behaviour and the relationship to microbiome composition. Wistar rats were injected with LPS (0.05 mg/kg) or saline (equivolume) on postnatal days 3 and 5. In adulthood, behavioural tests were performed to assess anxiety-like behaviour, and microbiota sequencing was performed on stool samples. There were distinctly different behavioural phenotypes for LPS-exposed males and females. LPS-exposed males displayed typical anxiety-like behaviours with significantly decreased social interaction (F(1,22) = 7.576, p = 0.009) and increased defecation relative to saline controls (F(1,23) = 8.623, p = 0.005). LPS-exposed females displayed a different behavioural phenotype with significantly increased social interaction (F(1,22) = 6.094, p = 0.018), and exploration (F(1,24) = 6.359, p = 0.015), compared to saline controls. With respect to microbiota profiling data, Bacteroidota was significantly increased for LPS-exposed females (F(1,14) = 4.931p = 0.035) and Proteobacteria was decreased for LPS-exposed rats of both sexes versus controls (F(1,30) = 4.923p = 0.035). Furthermore, alterations in predicted functional pathways for neurotransmitters in faeces were observed with a decrease in the relative abundance of D-glutamine and D-glutamate metabolism in LPS exposed females compared to control females (p < 0.05). This suggests that neonatal immune activation alters both later life behaviour and adult gut microbiota in sex-specific ways. These findings highlight the importance of sex in determining the impact of neonatal immune activation on social behaviour and the gut microbiota.
- Subject
- sex; faecal microbiota; anxiety; neonatal immune activation; gut brain axis; behaviour
- Identifier
- http://hdl.handle.net/1959.13/1480832
- Identifier
- uon:50574
- Identifier
- ISSN:0889-1591
- Language
- eng
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