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Investigating Intestinal Inflammation in DSS-induced Model of IBD
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Elevated Systemic Levels of Markers Reflecting Intestinal Barrier Dysfunction and Inflammasome Activation Are
Søren B Jensen1, Mashhood A Sheikh1, Ibrahim A Akkouh2,3
1Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.
Background And Hypothesis:
Gut microbiota alterations have been reported in severe mental illness (SMI) but fewer studies have probed for signs of gut barrier disruption and inflammation. We hypothesized that gut leakage of microbial products due to intestinal inflammation could contribute to systemic inflammasome activation in SMI.
Study Design:
We measured plasma levels of the chemokine CCL25 and soluble mucosal vascular addressin cell adhesion molecule-1 (sMAdCAM-1) as markers of T cell homing, adhesion and inflammation in the gut, lipopolysaccharide binding protein (LBP) and intestinal fatty acid binding protein (I-FABP) as markers of bacterial translocation and gut barrier dysfunction, in a large SMI cohort (n = 567) including schizophrenia (SCZ, n = 389) and affective disorder (AFF, n = 178), relative to healthy controls (HC, n = 418). We assessed associations with plasma IL-18 and IL-18BPa and leukocyte mRNA expression of NLRP3 and NLRC4 as markers of inflammasome activation.
Study Results:
Our main findings were: (1) higher levels of sMAdCAM-1 (P = .002), I-FABP (P = 7.6E-11), CCL25 (P = 9.6E-05) and LBP (P = 2.6E-04) in SMI compared to HC in age, sex, BMI, CRP and freezer storage time adjusted analysis; (2) the highest levels of sMAdCAM-1 and CCL25 (both P = 2.6E-04) were observed in SCZ and I-FABP (P = 2.5E-10) and LBP (3) in AFF; and (3), I-FABP correlated with IL-18BPa levels and LBP correlated with NLRC4.
Conclusions:
Our findings support that intestinal barrier inflammation and dysfunction in SMI could contribute to systemic inflammation through inflammasome activation.
Insights
Severe mental illness (SMI) is linked to gut barrier dysfunction and inflammation. This study found increased gut leakage markers in SMI patients, suggesting a role in systemic inflammation and inflammasome activation.
Area of Science:
- Neuroscience
- Gastroenterology
- Immunology
Background:
- Severe mental illness (SMI) is associated with gut microbiota changes.
- Limited research has explored gut barrier disruption and inflammation in SMI.
- This study investigates the link between gut leakage, inflammation, and inflammasome activation in SMI.
Purpose of the Study:
- To assess gut barrier integrity and inflammation markers in individuals with SMI.
- To explore the association between gut dysfunction markers and systemic inflammasome activation markers.
- To differentiate these markers between schizophrenia (SCZ) and affective disorder (AFF) within the SMI cohort.
Main Methods:
- Plasma levels of CCL25, soluble mucosal vascular addressin cell adhesion molecule-1 (sMAdCAM-1), lipopolysaccharide binding protein (LBP), and intestinal fatty acid binding protein (I-FABP) were measured.
- Inflammasome activation markers (IL-18, IL-18BPa, NLRP3, NLRC4) were assessed in plasma and leukocytes.
- A large cohort of SMI patients (n=567) and healthy controls (HC, n=418) were included.
Main Results:
- SMI patients exhibited significantly higher levels of sMAdCAM-1, I-FABP, CCL25, and LBP compared to HC.
- Schizophrenia (SCZ) patients showed the highest levels of sMAdCAM-1 and CCL25.
- Affective disorder (AFF) patients had the highest levels of I-FABP and LBP.
- I-FABP correlated with IL-18BPa, and LBP correlated with NLRC4.
Conclusions:
- Findings suggest intestinal barrier inflammation and dysfunction contribute to systemic inflammation in SMI.
- Gut leakage of microbial products may drive inflammasome activation in SMI.
- These results highlight a potential gut-brain axis mechanism in severe mental illness.
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