How Substance Use Effects the Gut-Brain Axis in Schizophrenia

Researchers sought to characterize the effects of tobacco, alcohol, and cannabis use on the gut-brain axis in patients with schizophrenia, noting that this topic has been largely unexplored despite published evidence of the bidirectional link between the gut microbiota and the brain, the frequent gastrointestinal microbiome alterations in patients with severe mental disorders, and the negative effects of substance use on intestinal permeability and the central nervous system.

The researchers, presenting during the American Psychiatric Association 2023 Annual Meeting poster sessions, found that smoking had a negative impact on systemic immune activation of intestinal microbial translocation, assessed via plasma-soluble CD14 levels. Conversely, cannabis and alcohol were not associated with changes in intestinal permeability among patients with schizophrenia.

This cross-sectional study included 80 outpatients (mean age, 42.88±12.78 years; 59.4% male) with schizophrenia diagnosed per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Demographic and clinical information was assessed with ad hoc questionnaires and Clinical Global Impressions Scale-Severity score. Lipopolysaccharide binding protein (LBP) levels were also evaluated.

Among the participants, 35% were smokers (mean daily cigarette consumption, 14.36±6.389), 18.5% consumed alcohol weekly, and 7.5% had used cannabis in the last month. Notably, researchers found statistically significant differences between smokers and nonsmokers in soluble CD14 levels (1.81±0.38 vs 2.04±4.2; F-test=0.613; P=.020), though not LBP levels (13.64±4.48 vs 14.08±5.30; F-test=0.019; P=.713).

Researchers also identified a negative correlation between number of cigarettes and CD14 levels that was close to statistical significance (r=–0.217; P=.053); however, they noted when groups were stratified by nonsmokers (n=23), light smokers (n=5), and heavy smokers (n=52), there were no significant differences between groups in CD14 or LBP.

After adjusting for age, sex, and length of illness in logistic regression models, tobacco remained associated with lower levels of plasma-soluble CD14 (odds ratio, 0.229; 95% CI, 0.058-0.908).

Ultimately, researchers suggested cigarette smoking had a negative impact on immune activation of bacterial translocation in patients with schizophrenia, while alcohol and cannabis use did not appear to impact intestinal permeability.