Increased levels of systemic LPS-positive bacterial extracellular vesicles in patients with intestinal barrier dysfunction

Tulkens, Joeri; Vergauwen, Glenn; Deun, Jan Van; Geeurickx, Edward; Dhondt, Bert; Lippens, Lien; Scheerder, Marie‐Angélique De; Miinalainen, Ilkka; Rappu, Pekka; Geest, Bruno G. De; Vandecasteele, Katrien; Laukens, Debby; Vandekerckhove, Linos; Denys, Hannelore; Vandesompele, Jo; Wever, Olivier De; Hendrix, An

doi:10.1136/gutjnl-2018-317726

Cited by 214 publications

(190 citation statements)

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“…Both BF-LPS and fragilysin can leak through the normally protective mucosal barriers of the GI-tract intestinal endothelium to induce substantial inflammatory pathology both systemically and after BBB transit into vulnerable CNS compartments, including the neocortical parenchyma of the brain (Fathi and Wu, 2016;Lukiw, 2016a,b;Zhao and Lukiw, 2018a,b;Barton et al, 2019;Batista et al, 2019;Fox et al, 2019;Sheppard et al, 2019;Zhao et al, 2019). Indeed, while Bacteroides fragilis is an anaerobic, Gram-negative, rod-shaped bacillus, and part of the normal microbiota of the human colon and is generally commensal, this microbe can cause a "smoldering" systemic infection if displaced into the bloodstream or surrounding tissue following disease, trauma or surgery (Hill et al, 2014a,b;Montagne et al, 2017;Tulkens et al, 2018;Erdo and Krajcsi, 2019;Fox et al, 2019;Patrick et al, 2019;Sarkar and Banerjee, 2019;Sweeney et al, 2019). When the highly toxic exudates of enterotoxigenic strains of B. fragilis escape the microbial-dense environment of the human GI-tract they can produce substantial systemic inflammatory pathology with significant mortality and morbidity.…”

Section: Gi-tract Exudates-bf-lps and Fragilysinmentioning

confidence: 99%

Gastrointestinal (GI) Tract Microbiome-Derived Neurotoxins—Potent Neuro-Inflammatory Signals From the GI Tract via the Systemic Circulation Into the Brain

Lukiw

2020

Front. Cell. Infect. Microbiol.

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Section: Gi-tract Exudates-bf-lps and Fragilysinmentioning

confidence: 99%

Gastrointestinal (GI) Tract Microbiome-Derived Neurotoxins—Potent Neuro-Inflammatory Signals From the GI Tract via the Systemic Circulation Into the Brain

Lukiw

2020

Front. Cell. Infect. Microbiol.

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“…[ 5 ] Additionally, the loss of intestinal barrier integrity directly affects the function of the intestinal barrier and results in the transportation of bacterial lipopolysaccharide (LPS) to the intestine, which activates a series of inflammatory reactions. [ 6 ] The consumption of HFD is reported to increase the intestinal abundance of Firmicutes . Some Firmicutes generate LPS that can convert bile acid into toxic deoxycholic acid (DCA).…”

Section: Introductionmentioning

confidence: 99%

Lonicera caerulea L. Polyphenols Alleviate Oxidative Stress‐Induced Intestinal Environment Imbalance and Lipopolysaccharide‐Induced Liver Injury in HFD‐Fed Rats by Regulating the Nrf2/HO‐1/NQO1 and MAPK Pathways

Cheng

Sun

et al. 2020

Molecular Nutrition Food Res

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Scope: This study investigates the modulatory effects of Lonicera caerulea L. polyphenols (LCPs) on the intestinal environment and lipopolysaccharide (LPS)-induced liver injury via the nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (HO-1)/NQO1 and mitogen-activated protein kinase (MAPK) pathways in a rat model of oxidative stress damage (OSD). Methods and results: To examine the prebiotic properties of LCP, a model of high-fat-diet-induced OSD is established using Sprague Dawley rats. In the colon, treatment with LCP for 8 weeks ameliorates enhanced intestinal permeability (glucagon-like peptide-2 content and occludin protein increase, whereas claudin-2 protein decreases), intestinal inflammation (levels of pro-inflammatory cytokines, such as tumor necrosis factor-, interleukin-6, cyclooxygenase-2, and nuclear factor kappa-B p65 (NF-B p65), decrease), and intestinal OSD (through regulation of the Nrf2/HO-1/NQO1 pathway). Moreover, LCP alleviates LPS-induced liver injury by suppressing the nuclear translocation of NF-B p65 and activation of the MAPK signaling pathway. Additionally, Bacilli, Lactobacillales, Lactobacillaceae, Lactobacillus, Akkermansia, Actinobacteria, Proteobacteria, Rothia, and Blautia are found to be the key intestinal microbial taxa related to intestinal OSD and LPS-induced liver injury in rats. Conclusion: LCP treatment potentially modulates the intestinal environment and alleviates liver injury by suppressing oxidative-stress-related pathways and altering the composition of the intestinal microbiota.

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“…A combination of size exclusion chromatography (SEC) and OptiPrep density gradient (DG) centrifugation was used to isolate EV from plasma. Sepharose CL-2B (GE Healthcare, Uppsala, Sweden, #17014001) was washed 3 times with PBS (Merck Millipore, Billerica, Massachusetts, USA) containing 0.32 % (w/v) trisodiumcitrate dihydrate (ChemCruz, Dallas, Texas, USA) 17 . For preparation of the SEC column, nylon filter with 20 µm pore size (Merck Millipore, Billerica, Massachusetts, USA) was placed on bottom of a 10 ml syringe (Romed, Wilnis, The Netherlands), followed by stacking of 10 ml Sepharose CL-2B.…”

Section: Methodsmentioning

confidence: 99%

Performance assessment of total RNA sequencing of human biofluids and extracellular vesicles

Everaert

Helsmoortel

Decock

et al. 2019

Preprint

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RNA profiling has emerged as a powerful tool to investigate the biomarker potential of 18 human biofluids. However, despite enormous interest in extracellular nucleic acids, RNA 19 sequencing methods to quantify the total RNA content outside cells are rare. Here, we evaluate the 20 performance of the SMARTer Stranded Total RNA-Seq method in human platelet-rich plasma, 21 platelet-free plasma, urine, conditioned medium, and extracellular vesicles (EVs) from these 22 biofluids. We found the method to be accurate, precise, compatible with low-input volumes and 23 able to quantify a few thousand genes. We picked up distinct classes of RNA molecules, including 24 mRNA, lncRNA, circRNA, miscRNA and pseudogenes. Notably, the read distribution and gene 25 content drastically differ among biofluids. In conclusion, we are the first to show that the SMARTer 26 method can be used for unbiased unraveling of the complete transcriptome of a wide range of 27 biofluids and their extracellular vesicles. 28 30 31 2 of 15 1. Introduction 33All human biofluids contain a multitude of extracellular nucleic acids, harboring a wealth of 34 information about health and disease status. In addition to established non-invasive prenatal testing 35 of fetal nucleic acids in maternal plasma 1 , liquid biopsies have emerged as a novel powerful tool in 36 the battle against cancer 2 . Although in the past most attention was given to circulating DNA, its more 37 dynamic derivate extracellular RNA may provide additional layers of information. However, RNA 38 sequencing in biofluids is technically challenging. Low input amounts, large dynamic range, and 39 (partial) degradation of RNA hamper straightforward quantification. While sequencing of small 40 RNAs 3 and targeted or capture sequencing of longer RNAs 4 proved to be successful, studies using 41 total RNA sequencing on biofluids are rare. To date, only a few whole transcriptome profiling 42 attempts were made on urine, plasma or extracellular vesicles 5-9 , quantifying both polyadenylated 43 and non-polyadenylated RNA transcripts. However, all these methods suffer from one or more 44 limitations such as short fragment length, low amount of quantified genes or ribosomal RNA 45 contamination. 47The advantages of total RNA sequencing are plentiful. Indeed, detection is not limited to a set of pre-48 defined targets, nor to (3' ends of) polyadenylated RNAs. Next to polyadenylated mRNAs, various 49 other RNA biotypes including circular RNAs, histone RNAs, and a sizable fraction of long non-50 coding RNAs can be distinguished. In addition, the study of posttranscriptional regulation is possible 51 by comparing exonic and intronic reads 10 . Altogether, this generates a much more comprehensive 52 view of the transcriptome. 54Here we aimed to assess the performance of a strand-specific total RNA library preparation 55 method for different types of biofluids and derived extracellular vesicles (EVs). We applied the 56 method on platelet-rich plasma, platelet-free plasma, urine and conditioned medium from...

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Increased levels of systemic LPS-positive bacterial extracellular vesicles in patients with intestinal barrier dysfunction

Cited by 214 publications

References 10 publications

Gastrointestinal (GI) Tract Microbiome-Derived Neurotoxins—Potent Neuro-Inflammatory Signals From the GI Tract via the Systemic Circulation Into the Brain

Gastrointestinal (GI) Tract Microbiome-Derived Neurotoxins—Potent Neuro-Inflammatory Signals From the GI Tract via the Systemic Circulation Into the Brain

Lonicera caerulea L. Polyphenols Alleviate Oxidative Stress‐Induced Intestinal Environment Imbalance and Lipopolysaccharide‐Induced Liver Injury in HFD‐Fed Rats by Regulating the Nrf2/HO‐1/NQO1 and MAPK Pathways

Performance assessment of total RNA sequencing of human biofluids and extracellular vesicles

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