title: Discordant patterns of bacterial translocation markers and implications for innate immune imbalances in schizophrenia.
abstract: The origin of inflammation in psychiatric disorders is not well understood. The translocation of commensal microbiota across the gastrointestinal barrier can result in a persistent state of low-grade immune activation and/or inflammation. We measured serological surrogate markers of bacterial translocation (soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP)) in two psychiatric cohorts and compared these levels to C-reactive protein (CRP), body mass index (BMI), and food-related and autoimmune antibodies. The two cohorts were composed of the following: (1) n=141 schizophrenia, n=75 bipolar disorder, n=78 controls; (2) n=78 antipsychotic-naïve first-episode schizophrenia, n=38 medicated first-episode schizophrenia. sCD14 seropositivity conferred a 3.1-fold increased odds of association with schizophrenia (multivariate regressions, OR=3.09, p<0.0001) compared to controls. Case-control differences in sCD14 were not matched by LBP. Quantitative levels of LBP, but not sCD14, correlated with BMI in schizophrenia (R(2)=0.21, p<0.0001). sCD14 and LBP also exhibited some congruency in schizophrenia with both significantly correlated with CRP (R(2)=0.26-0.27, p<0.0001) and elevated in females compared to males (p<0.01). Antipsychotic treatment generally did not impact sCD14 or LBP levels except for significant correlations, especially sCD14, with gluten antibodies in antipsychotic-naïve schizophrenia (R(2)=0.27, p<0.0001). In bipolar disorder, sCD14 levels were significantly correlated with anti-tissue transglutaminase IgG (R(2)=0.37, p<0.001). In conclusion, these bacterial translocation markers produced discordant and complex patterns of activity, a finding that may reflect an imbalanced, activated innate immune state. Whereas both markers may upregulate following systemic exposure to Gram-negative bacteria, non-lipopolysaccharide-based monocyte activation, autoimmunity and metabolic dysfunction may also contribute to the observed marker profiles.
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 1105, Baltimore, MD 21287-4933, USA. eseverance@jhmi.edu
authors.forename: Emily G
authors.initials: EG
authors.lastname: Severance
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Gressitt
authors.forename: Cassie R
authors.initials: CR
authors.lastname: Stallings
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Origoni
authors.forename: Sunil
authors.initials: S
authors.lastname: Khushalani
authors.forename: F Markus
authors.initials: FM
authors.lastname: Leweke
authors.forename: Faith B
authors.initials: FB
authors.lastname: Dickerson
authors.forename: Robert H
authors.initials: RH
authors.lastname: Yolken
mesh_terms: D000209:Acute-Phase Proteins; D000328:Adult; D000704:Analysis of Variance; D001323:Autoantibodies / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood / Q000276:immunology; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D012044:Regression Analysis; D012559:Schizophrenia / Q000097:blood* / Q000276:immunology*; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D001323:Autoantibodies; D002097:C-Reactive Protein; D002352:Carrier Proteins; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein
keywords: BMI; C-reactive protein; CRP; Diet; GI; Gut; LBP; LPS; Macrophage; Mental illness; Metabolic syndrome; Microbiome; Psychosis; body mass index; gastrointestinal; lipopolysaccharide; lipopolysaccharide binding protein; sCD14; soluble CD14; tTG; tissue transglutaminase