TBA (24S107)

Of Bowels, Brain and Behaviour: Focus on the Role of the Microbiome-Gut-Brain Axis in Resilience and Vulnerability

Author(s)

L. Wilmes 1,2,3, V. Caputi 1,2, T. F. S. Bastiaanssen 1,2, J. M. Collins 1,2, S. M. O’Mahony 1,2, J. F. Cryan 1,2, G. Clarke 1,3

Department(s)/Institutions

1 - APC Microbiome Ireland, University College Cork, Cork, Ireland 2 - Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland 3 - Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland

Introduction

The gut-brain axis facilitates bidirectional communication between gut bacteria and the brain to regulate homeostatic functions. Early-life stress (ELS) in rats modulates gut function and behaviours relevant for psychiatric comorbidity in irritable bowel syndrome. Similar to the clinical population, not all animals exposed to ELS present the full repertoire of gastrointestinal and CNS phenotypes in adulthood.

Aims/Background

We aim to identify the role of the gut microbiota in explaining the susceptibility to distinct pathophysiological consequences of ELS.

Method

Rat offspring was subjected to maternal separation (MS) and faecal samples in early-life were used for 16S-sequencing. Adult offspring visceral pain sensitivity and depression-like behaviour was assessed. Behavioural data were processed in a two-step cluster analysis to identify natural groupings. Faecal microbiota transplantation (FMT) into naïve animals was performed, to establish a causal link between gut microbiota configurations and behavioural responses.

Results

MS results in increased visceral hypersensitivity while showing a trend for a sex specific effect in depression-like behaviours. The cluster analysis revealed four cluster within the behavioural dataset representing distinct pathophysiological domains as a consequence of ELS: resilient, pain, depression-like and comorbid. The microbiota shows alterations at the level of composition and predicted functions. FMT from the different clusters into naïve animals partially transfers depression-like and pain behaviours in the recipient animals.

Conclusions

Our study is the first to identify a role of the gut microbiota in gut-brain phenotypes showing susceptibility to the distinct consequences of ELS. Ongoing research investigates the role of the microbiota in a clinical IBS population.