Gut permeability and low-grade inflammation in bipolar disorder

Abstract

Introduction Systemic inflammation has been increasingly related to bipolar disorder -BD- (Tanaka et al. Neurosci Res 2017;115 59-63). Intestinal bacterial translocation has been postulated as one of the causes of this inflammation (Nguyen et al. J Psychiatr Res 2018;99 50-61). A possible pathway is through the lipopolysaccharide, which is presented to CD14 through lipopolysaccharide binding protein (LBP) leading to a release of systemic inflammatory markers like C-reactive protein (CPR) (Funda et al. Infect Immun 2001;69 3772-81). Objectives 1) Describe gut permeability in patients with BD through the determination of intestinal inflammatory markers (LBP, sCD14) in plasma; 2) Analyze variables associated with intestinal inflammation. Methods Cross-sectional study of 38 patients with BD [mean age=45.50 (SD=10.93; range 23-68); males=15 (39.5%)], recruited from mental health outpatient clinics in Oviedo (Spain). Assessment: Pro-inflammation biomarkers [CRP (mg/dL), Erythrocyte Sedimentation Rate (ESR) (mm/h), Neutrophil/Lymphocyte, Monocyte/Lymphocyte, Platelet/Lymphocyte and Systemic Immune Inflammation Indexes]. Indirect markers of intestinal bacterial translocation [LBP, soluble CD14 (sCD14)]. Dichotomous variables were created for LBP, considering LBP ≥15 μg/dL as increased gut permeability; and for CPR, considering CRP≥0.3 as systemic inflammation. Metabolic syndrome [ATPIII criteria: glucose, HDL, triglycerides (mg/dl), arterial pressure (mmHg), abdominal circumference (cm)], body mass index (BMI) (kg/m2), smoking, cannabis or alcohol use. Statistical analyses: t-Student test, multiple linear regression analyses. Results Average LBP was 14.60 μg/dL (SD=6.4) and 15 patients (39.5%) had increased gut permeability. Moreover, average CPR was 0.40 mg/dL (SD=0.58) and 16 patients (47.1%) showed systemic inflammation. There were no patients with increased levels of sCD14. Associations were found between LBP and CPR (r=0.357; p=0.032), cannabis use in the last month (t=-2.293; p=0.029), BMI (r=0.433; p=0.008) and abdominal obesity (t=3.006; p=0.005); but no with age or sex. Subsequently, a multiple linear regression model for LBP was calculated with variables previously mentioned, and age (based on expert criteria). The overall regression was statistically significant (R2=0.49, F=9.273, p<0.001). It was found that CPR, abdominal obesity, and cannabis use in the last month significantly predicted LBP levels (table 1). Table 1. Multiple linear regression analyses to LBP B SE β t p CPR 4.842 1.529 0.439 3.167 0.004 Abdominal obesity 4.810 1.849 0.362 2.601 0.014 Cannabis use -5.048 2.273 -0.296 -2.221 0.034 Conclusions More than one third of patients with BD had increased gut permeability. Almost 50% had systemic inflammation. Intestinal permeability was directly related to abdominal obesity and systemic inflammation, but inversely related to cannabis use. Disclosure of Interest None Declared