An investigation into the interaction of the microbiome-gut-brain axis with stress : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Nutritional Science at Massey University, Manawatū, New Zealand
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2023
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Massey University
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This thesis aimed to investigate whether changes in the gut microbiota and associated biomarkers were associated with stress-induced anxiety-like and depressive-like behaviour.
Two studies used the unpredictable chronic mild stress (UCMS) over 4 or 6 weeks (vs no UCMS, control) in Sprague-Dawley rats. Depressive-like behaviour was measured in female rats using the sucrose preference test, and the Porsolt swim test. Anxiety-like behaviour was measured with the light-dark box test. Faecal corticosterone, caecal microbiota (composition and organic acids), serum gut permeability (lipopolysaccharide-binding protein, LBP) and plasma inflammation (12 cytokines) markers were measured.
Atypical behaviours were observed in female rats following UCMS and no depressive-like behaviours were observed. The circulating concentration of cytokines, but not plasma LBP or caecal organic acids, was higher in UCMS-exposed female rats. Relative abundance of taxa from the Clostridiales order and Desulfovibrionaceae family correlated with anxiety-like behaviours and plasma cytokine concentrations, regardless of UCMS.
Studies of these atypical behaviours in female rats confirmed expected patterns of sucrose intake in the sucrose preference test and no decreased depressive-like behaviours in the Porsolt swim test with antidepressant citalopram and imipramine drugs. A further study also showed differences in baseline behaviour in male versus female rats, leading the second UCMS study to be in male rats.
Increased faecal corticosterone and anxiety-like behaviours were observed in male UCMS-exposed and control rats at week 4 of UCMS compared to baseline. Plasma cytokine concentrations were higher in the UCMS group but higher faecal corticosterone concentrations and anxiety behaviours in control rats suggest that they were more stressed than treated rats. Caecal neurotransmitter concentrations did not differ between treatments nor correlate with serum neurotransmitter, cytokines or LBP concentrations or behaviour.
The findings showed an association between the gut microbiota and anxiety-like behaviours, which was not stress dependent. No measured biomarkers explained the observed anxiety-like behaviours. Caecal digesta neurotransmitter profiles were dissimilar to serum profiles indicating it may not be an important influence on serum levels. Despite the atypical behavioural results following the interventions, the results still provided useful and unique information which contributes to the body of Microbiome Gut Brain Axis research.
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Gastrointestinal system, Microbiology, Stress (Psychology), Affective disorders, Animal models