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Letter
Increased levels of systemic LPS-positive bacterial extracellular vesicles in patients with intestinal barrier dysfunction
  1. Joeri Tulkens1,2,
  2. Glenn Vergauwen1,2,3,
  3. Jan Van Deun1,2,
  4. Edward Geeurickx1,2,
  5. Bert Dhondt1,2,4,
  6. Lien Lippens1,2,5,
  7. Marie-Angélique De Scheerder6,
  8. Ilkka Miinalainen7,
  9. Pekka Rappu8,
  10. Bruno G De Geest2,9,
  11. Katrien Vandecasteele2,10,
  12. Debby Laukens11,12,
  13. Linos Vandekerckhove6,
  14. Hannelore Denys2,5,
  15. Jo Vandesompele2,13,
  16. Olivier De Wever1,2,
  17. An Hendrix1,2
  1. 1Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University, Ghent, Belgium
  2. 2Cancer Research Institute Ghent, Ghent University, Ghent, Belgium
  3. 3Department of Gynaecology, Ghent University Hospital, Ghent, Belgium
  4. 4Department of Urology, Ghent University Hospital, Ghent, Belgium
  5. 5Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium
  6. 6Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium
  7. 7Biocenter Oulu, University of Oulu, Oulu, Finland
  8. 8Department of Biochemistry, University of Turku, Turku, Finland
  9. 9Department of Pharmaceutics, Ghent University, Ghent, Belgium
  10. 10Department of Radiation Oncology and Experimental Cancer Research, Ghent University, Ghent, Belgium
  11. 11Department of Gastroenterology, Ghent University, Ghent, Belgium
  12. 12Ghent Gut Inflammation Group, Ghent University, Ghent, Belgium
  13. 13Center for Medical Genetics, Ghent University, Ghent, Belgium
  1. Correspondence to Prof An Hendrix, Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University, Ghent 9000, Belgium; an.hendrix{at}ugent.be

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We read with interest recent papers reporting on the impact of gut microbiota on several aspects of health and disease due to altered intestinal permeability resulting in systemic immune activation by pathogen-associated molecular patterns (PAMP), a process termed microbial translocation.1–4 Common to these studies is the analysis of systemic lipopolysaccharide (LPS), the major outer membrane PAMP of Gram-negative bacteria, to quantitatively assess microbial translocation. While systemic LPS is typically regarded as a soluble product, either or not neutralised by lipoproteins and endotoxin core antibodies, LPS is also released as a membrane-associated PAMP through extracellular vesicles (EV).5–7 Bacterial EV are nanometre-sized membrane particles transporting nucleic acids, metabolites, proteins and endotoxins.8 As such, bacterial EV that enter the systemic circulation may deliver and elicit a variety of immunological and metabolic responses in different organs including the brain.9 To date, the systemic presence and activity of bacterial EV in patients with intestinal barrier dysfunction have not been investigated.

Here, we fractionated plasma of 49 subjects to distinguish bacterial EV-associated LPS from other LPS products (online supplementary file 1 …

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