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Discordant patterns of bacterial translocation markers and implications for innate immune imbalances in schizophrenia
Open accessAbstract
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.
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“Researchers at Johns Hopkins University School of Medicine found evidence of increased gut bacterial translocation in schizophrenic patients, unrelated to antipsychotic treatment.”
From The Gut Microbiome and the Brain (2014) · cites this paper as [42]
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“suggesting that gut bacterial components other than LPS may be stimulating monocyte activation and inflammation in schizophrenics.42”
From The Gut Microbiome and the Brain (2014) · cites this paper as [42]
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“Presence of the translocation marker soluble CD14 tripled the risk of schizophrenia and was positively associated with C-reactive protein (CRP) but not with LPS-binding protein (LBP)”
From The Gut Microbiome and the Brain (2014) · cites this paper as [42]
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König, J., Wells, J. M., Cani, P. D., García‐Ródenas, C. L., MacDonald, T. T., Mercenier, A., Whyte, J., Troost, F. J., & Brummer, R. J. (2016) · Clinical and Translational Gastroenterology · doi:10.1038/ctg.2016.54 · Cited by 811
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Metadata
- Authors
- Severance, E. G., Gressitt, K. L., Stallings, C. R., Origoni, A. E., Khushalani, S., Leweke, F. M., Dickerson, F. B., & Yolken, R. H.
- Affiliations
- Johns Hopkins University (US)
- Sheppard and Enoch Pratt Hospital (US)
- University of Cologne (DE)
- Corresponding author
- Severance, Emily G.
- ORCID
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 148
- Issue
- 1-3
- Pages
- 130-137
- ISSN
- 0920-9964 (ISSN-L)
- PMC
- PMC3732507
- OpenAlex
- W2106172174
- Cited by
- 243
- References
- 74
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 18 · 2023: 22 · 2022: 13 · 2021: 23 · 2020: 23 · 2019: 23 · 2018: 22 · 2017: 17 · 2016: 24 · 2015: 19 · 2014: 13 · 2013: 3
- FWCI
- 6.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Schizophrenia Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH‑94268, P50MH094268)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K08HD073315)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- bacterial translocation, soluble CD14
- MeSH terms
- Lipopolysaccharide-Binding Protein, Acute-Phase Proteins, Adult, Analysis of Variance, Autoantibodies, Bipolar Disorder, C-Reactive Protein, Carrier Proteins, Female, Humans, Male, Membrane Glycoproteins, Regression Analysis, Schizophrenia, Cohort Studies, Body Mass Index, Lipopolysaccharide Receptors
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