# Poster Session II - A226 SYSTEMIC INFLAMMATORY PATHWAYS LINK LOW BRAIN CORTICAL OXYGENATION TO SYMPTOM SEVERITY IN CROHN’S DISEASE

## TL;DR

Crohn’s disease patients have lower brain oxygen levels linked to worse sleep and inflammation, suggesting a brain-body connection.

## Contribution

This study is the first to link low prefrontal cortex oxygenation with systemic RANTES levels and symptoms in Crohn’s disease.

## Key findings

- CD patients had significantly lower prefrontal cortex oxygenation compared to healthy controls.
- Low brain oxygen was associated with worse sleep quality and interoceptive awareness in CD patients.
- RANTES levels partially mediated the relationship between brain oxygen and sleep quality in CD.

## Abstract

Patients with Crohn’s disease (CD) experience altered interoception and poor sleep quality. The prefrontal cortex (PFC), which regulates both processes, shows low oxygenation, quantified by tissue oxygen saturation (StO2) using frequency-domain near-infrared spectroscopy (FD-NIRS), and has been linked to inflammation-related symptoms in Multiple Sclerosis and Long-COVID. However, this relationship has not been explored in CD, and its mechanisms remain unclear.

To assess the impact of CD on PFC StO2 and examine its associations with patient-reported outcome (PROs) and circulating biomarkers.

Healthy controls (HC; n=19, age 41±15) and CD patients categorized by the Harvey–Bradshaw Index into remitted (rCD; n=16, age 51±14) and active disease (aCD; n=10, age 47±15) were recruited. Resting-state PFC StO2 was measured using FD-NIRS. CD patients completed the Multidimensional Assessment of Interoceptive Awareness (MAIA) and Pittsburgh Sleep Quality Index (PSQI) questionnaires. Plasma cytokine/chemokine levels were quantified using multiplex assays. Between-group StO2 differences were tested using ANCOVA (age-controlled). Spearman and Pearson correlations assessed StO2 associations with PROs and cytokines, respectively, and mediation analyses evaluated pathways linking StO2 and PROs with cytokines as mediators.

PFC StO2 was significantly lower in the rCD patients compared to HCs (p=0.017; Table 1). Across all CD patients, StO2 showed a moderate negative association with the MAIA attention regulation subscale (ignoring, distraction) (ρ=-0.63, p=0.004) and PSQI-evaluated sleep quality (ρ=-0.52, p=0.031) (Fig. 1A and B). Controlling for disease activity and age, PFC StO2 had a significant negative correlation with RANTES levels (r=-0.56, p=0.004) (Fig. 1C). Mediation analysis identified RANTES as a significant mediator of the StO2-PSQI relationship (p=0.020), accounting for 29% of the total effect.

We found that CD patients have low PFC StO2 associated with altered interoceptive awareness and poor sleep quality; changes potentially mediated, at least in part, through systemic RANTES (Regulated on Activation, Normal T-Cell Expressed and Secreted; a proinflammatory chemokine) signalling to the brain. Our novel findings suggest a potential link between low PFC oxygen, systemic inflammation, and adverse symptoms in CD. FD-NIRS may provide a non-invasive method to study the association between CD-associated systemic inflammatory changes and symptom burden.

A226 Table 1: Summary of StO2 Values

CIHR