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Gut Leakage of Fungal-Derived Inflammatory Mediators: Part of a Gut-Liver-Kidney Axis in Bacterial Sepsis

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Abstract

Sepsis is a life-threatening response to systemic infection. In addition to frank gastrointestinal (GI) rupture/puncture, sepsis can also be exacerbated by translocation of pathogen-associated molecular patterns (PAMPs) from the GI tract to the systemic circulation (gut origin of sepsis). In the human gut, Gram-negative bacteria and Candida albicans are abundant, along with their major PAMP components, endotoxin (LPS) and (1 → 3)-β-d-glucan (BG). Whereas the influence of LPS in bacterial sepsis has been studied extensively, exploration of the role of BG in bacterial sepsis is limited. Post-translocation, PAMPs enter the circulation through lymphatics and the portal vein, and are detoxified and then excreted via the liver and the kidney. Sepsis-induced liver and kidney injury might therefore affect the kinetics and increase circulating PAMPs. In this article, we discuss the current knowledge of the impact of PAMPs from both gut mycobiota and microbiota, including epithelial barrier function and the “gut-liver-kidney axis,” on bacterial sepsis severity.

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Funding

Chulalongkorn University Office of International Affairs Scholarship for Short-term Research and Ratchadapisek Somphot Fund for Postdoctoral Fellowship, Chulalongkorn University.

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Authors and Affiliations

  1. Immunology Unit, Department of Microbiology, Chulalongkorn University, Bangkok, 10330, Thailand

    Panomwat Amornphimoltham & Asada Leelahavanichkul

  2. Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

    Peter S. T. Yuen & Robert A. Star

  3. Center of Excellence in Immunology and Immune-mediated Diseases, Department of Microbiology, Chulalongkorn University, Bangkok, Thailand

    Asada Leelahavanichkul

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  1. Panomwat Amornphimoltham
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  2. Peter S. T. Yuen
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  3. Robert A. Star
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  4. Asada Leelahavanichkul
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Correspondence to Asada Leelahavanichkul.

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Amornphimoltham, P., Yuen, P.S.T., Star, R.A. et al. Gut Leakage of Fungal-Derived Inflammatory Mediators: Part of a Gut-Liver-Kidney Axis in Bacterial Sepsis. Dig Dis Sci 64, 2416–2428 (2019). https://doi.org/10.1007/s10620-019-05581-y

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