Administration of galacto-oligosaccharide prebiotics in the Flinders Sensitive Line animal model of depression.

Introduction: Major depressive disorder is the leading source of disability globally and current pharmacological treatments are less than adequate. Animal models such as the Flinders Sensitive Line (FSL) rats are used to mimic aspects of the phenotype in the human disorder and to characterise candidate antidepressant agents. Communication between the gut microbiome and the brain may play an important role in psychiatric disorders such as depression. Interventions targeting the gut microbiota may serve as potential treatments for depression, and this drives increasing research into the effect of probiotics and prebiotics in neuropsychiatric disorders. Prebiotics, galacto-oligosaccharides and fructooligosaccharides that stimulate the activity of gut bacteria have been reported to have a positive impact, reducing anxiety and depressive-like phenotypes and stress-related physiology in mice and rats, as well as in humans. Bimuno, the commercially available beta-galacto-oligosaccharide, has been shown to increase gut microbiota diversity.

Aim: Here, we aim to investigate the effect of Bimuno on rat anxiety-like and depressive-like behaviour and gut microbiota composition in the FSL model, a genetic model of depression, in comparison to their control, the Flinders Resistant Line (FRL) rats.

Methods: Sixty-four male rats aged 5-7 weeks, 32 FSL and 32 FRL rats, will be randomised to receive Bimuno or control (4 g/kg) daily for 4 weeks. Animals will be tested by an experimenter unaware of group allocation on the forced swim test to assessed depressive-like behaviour, the elevated plus maze to assess anxiety-like behaviour and the open field test to assess locomotion. Animals will be weighed and food and water intake, per kilogram of bodyweight, will be recorded. Faeces will be collected from each animal prior to the start of the experiment and on the final day to assess the bacterial diversity and relative abundance of bacterial genera in the gut. All outcomes and statistical analysis will be carried out blinded to group allocation, group assignments will be revealed after raw data have been uploaded to Open Science Framework. Two-way analysis of variance will be carried out to investigate the effect of treatment (control or prebiotic) and strain (FSL or FRL) on depressive-like and anxiety-like behaviours.