Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain

Through the use of RNA sequencing, microRNA (miRNA) and messenger RNA (mRNA) microfluidic array analysis, LED Northern, Western and ELISA analysis and multiple bioinformatics algorithms we have discovered a novel route for pathogenic communication between the human gastrointestinal (GI)-tract microbiome and the brain. The evidence suggests that this pathogenic gut-brain circuit involves: (i) lipopolysaccharide (LPS) from the GI-tract resident enterotoxigenic Gram-negative bacteria Bacteroides fragilis (BF-LPS); (ii) LPS transit across the GI-tract barrier into the systemic circulation; (iii) transport of a highly pro-inflammatory systemic BF-LPS across the blood-brain barrier (BBB) into the brain-parenchyma and neuronal-cytoplasm; (iv) activation and signaling via the pro-inflammatory NF-kB (p50/p65) transcription-factor complex; (v) NF-kB-coupling and significant up-regulation of the inducible pro-inflammatory microRNA-146a (miRNA-146a) and microRNA-155 (miRNA-155); each containing multiple NF-kB DNA-binding and activation sites in their immediate promoters; and (vi) subsequent down-regulation of miRNA-146a-miRNA-155 regulated mRNA targets such as that encoding complement factor H (CFH), a soluble complement control glycoprotein and key repressor of the innate-immune response. Down-regulated CFH expression activates the complement-system, the major non-cellular component of the innate-immune system while propagating neuro-inflammation. Other GI-tract microbes and their highly complex pro-inflammatory exudates may contribute to this pathogenic GI-tract-brain pathway. We speculate that it may be significant that the first Gram-negative anaerobic bacterial species intensively studied as a potential contributor to the onset of Alzheimer’s disease (AD), that being the bacillus Bacteroides fragilis appears to utilize damaged or leaky physiological barriers and an activated NF-kB (p50-p65) – pro-inflammatory miRNA-146a-miRNA-155 signaling circuit to convey microbiome-derived pathogenic signals into the brain. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Peter Alexandrov [verfasserIn] Yuhai Zhao [verfasserIn] Wenhong Li [verfasserIn] Walter Lukiw [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	alzheimer’s disease bacteroides fragilis (b. fragilis) complement factor h (cfh) dysbiosis microrna-146a microrna-155 nf-kb (p50/p65)

Übergeordnetes Werk:	In: Folia Neuropathologica - Termedia Publishing House, 2016, 57(2019), 3, Seite 211-219
Übergeordnetes Werk:	volume:57 ; year:2019 ; number:3 ; pages:211-219

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.5114/fn.2019.88449

Katalog-ID:	DOAJ066505526

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allfields	10.5114/fn.2019.88449 doi (DE-627)DOAJ066505526 (DE-599)DOAJ77a16bc6e2ef4e82a02b4fd6906642d8 DE-627 ger DE-627 rakwb eng Peter Alexandrov verfasserin aut Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Through the use of RNA sequencing, microRNA (miRNA) and messenger RNA (mRNA) microfluidic array analysis, LED Northern, Western and ELISA analysis and multiple bioinformatics algorithms we have discovered a novel route for pathogenic communication between the human gastrointestinal (GI)-tract microbiome and the brain. The evidence suggests that this pathogenic gut-brain circuit involves: (i) lipopolysaccharide (LPS) from the GI-tract resident enterotoxigenic Gram-negative bacteria Bacteroides fragilis (BF-LPS); (ii) LPS transit across the GI-tract barrier into the systemic circulation; (iii) transport of a highly pro-inflammatory systemic BF-LPS across the blood-brain barrier (BBB) into the brain-parenchyma and neuronal-cytoplasm; (iv) activation and signaling via the pro-inflammatory NF-kB (p50/p65) transcription-factor complex; (v) NF-kB-coupling and significant up-regulation of the inducible pro-inflammatory microRNA-146a (miRNA-146a) and microRNA-155 (miRNA-155); each containing multiple NF-kB DNA-binding and activation sites in their immediate promoters; and (vi) subsequent down-regulation of miRNA-146a-miRNA-155 regulated mRNA targets such as that encoding complement factor H (CFH), a soluble complement control glycoprotein and key repressor of the innate-immune response. Down-regulated CFH expression activates the complement-system, the major non-cellular component of the innate-immune system while propagating neuro-inflammation. Other GI-tract microbes and their highly complex pro-inflammatory exudates may contribute to this pathogenic GI-tract-brain pathway. We speculate that it may be significant that the first Gram-negative anaerobic bacterial species intensively studied as a potential contributor to the onset of Alzheimer’s disease (AD), that being the bacillus Bacteroides fragilis appears to utilize damaged or leaky physiological barriers and an activated NF-kB (p50-p65) – pro-inflammatory miRNA-146a-miRNA-155 signaling circuit to convey microbiome-derived pathogenic signals into the brain. alzheimer’s disease bacteroides fragilis (b. fragilis) complement factor h (cfh) dysbiosis microrna-146a microrna-155 nf-kb (p50/p65) Medicine R Yuhai Zhao verfasserin aut Wenhong Li verfasserin aut Walter Lukiw verfasserin aut In Folia Neuropathologica Termedia Publishing House, 2016 57(2019), 3, Seite 211-219 (DE-627)511229119 (DE-600)2233184-0 1509572X nnns volume:57 year:2019 number:3 pages:211-219 https://doi.org/10.5114/fn.2019.88449 kostenfrei https://doaj.org/article/77a16bc6e2ef4e82a02b4fd6906642d8 kostenfrei https://www.termedia.pl/Lipopolysaccharide-stimulated-NF-kB-miRNA-146a-and-miRNA-155-mediated-molecular-genetic-communication-between-the-human-gastrointestinal-tract-microbiome-and-the-brain,20,37898,1,1.html kostenfrei https://doaj.org/toc/1641-4640 Journal toc kostenfrei https://doaj.org/toc/1509-572X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 57 2019 3 211-219
spelling	10.5114/fn.2019.88449 doi (DE-627)DOAJ066505526 (DE-599)DOAJ77a16bc6e2ef4e82a02b4fd6906642d8 DE-627 ger DE-627 rakwb eng Peter Alexandrov verfasserin aut Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Through the use of RNA sequencing, microRNA (miRNA) and messenger RNA (mRNA) microfluidic array analysis, LED Northern, Western and ELISA analysis and multiple bioinformatics algorithms we have discovered a novel route for pathogenic communication between the human gastrointestinal (GI)-tract microbiome and the brain. The evidence suggests that this pathogenic gut-brain circuit involves: (i) lipopolysaccharide (LPS) from the GI-tract resident enterotoxigenic Gram-negative bacteria Bacteroides fragilis (BF-LPS); (ii) LPS transit across the GI-tract barrier into the systemic circulation; (iii) transport of a highly pro-inflammatory systemic BF-LPS across the blood-brain barrier (BBB) into the brain-parenchyma and neuronal-cytoplasm; (iv) activation and signaling via the pro-inflammatory NF-kB (p50/p65) transcription-factor complex; (v) NF-kB-coupling and significant up-regulation of the inducible pro-inflammatory microRNA-146a (miRNA-146a) and microRNA-155 (miRNA-155); each containing multiple NF-kB DNA-binding and activation sites in their immediate promoters; and (vi) subsequent down-regulation of miRNA-146a-miRNA-155 regulated mRNA targets such as that encoding complement factor H (CFH), a soluble complement control glycoprotein and key repressor of the innate-immune response. Down-regulated CFH expression activates the complement-system, the major non-cellular component of the innate-immune system while propagating neuro-inflammation. Other GI-tract microbes and their highly complex pro-inflammatory exudates may contribute to this pathogenic GI-tract-brain pathway. We speculate that it may be significant that the first Gram-negative anaerobic bacterial species intensively studied as a potential contributor to the onset of Alzheimer’s disease (AD), that being the bacillus Bacteroides fragilis appears to utilize damaged or leaky physiological barriers and an activated NF-kB (p50-p65) – pro-inflammatory miRNA-146a-miRNA-155 signaling circuit to convey microbiome-derived pathogenic signals into the brain. alzheimer’s disease bacteroides fragilis (b. fragilis) complement factor h (cfh) dysbiosis microrna-146a microrna-155 nf-kb (p50/p65) Medicine R Yuhai Zhao verfasserin aut Wenhong Li verfasserin aut Walter Lukiw verfasserin aut In Folia Neuropathologica Termedia Publishing House, 2016 57(2019), 3, Seite 211-219 (DE-627)511229119 (DE-600)2233184-0 1509572X nnns volume:57 year:2019 number:3 pages:211-219 https://doi.org/10.5114/fn.2019.88449 kostenfrei https://doaj.org/article/77a16bc6e2ef4e82a02b4fd6906642d8 kostenfrei https://www.termedia.pl/Lipopolysaccharide-stimulated-NF-kB-miRNA-146a-and-miRNA-155-mediated-molecular-genetic-communication-between-the-human-gastrointestinal-tract-microbiome-and-the-brain,20,37898,1,1.html kostenfrei https://doaj.org/toc/1641-4640 Journal toc kostenfrei https://doaj.org/toc/1509-572X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 57 2019 3 211-219
allfields_unstemmed	10.5114/fn.2019.88449 doi (DE-627)DOAJ066505526 (DE-599)DOAJ77a16bc6e2ef4e82a02b4fd6906642d8 DE-627 ger DE-627 rakwb eng Peter Alexandrov verfasserin aut Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Through the use of RNA sequencing, microRNA (miRNA) and messenger RNA (mRNA) microfluidic array analysis, LED Northern, Western and ELISA analysis and multiple bioinformatics algorithms we have discovered a novel route for pathogenic communication between the human gastrointestinal (GI)-tract microbiome and the brain. The evidence suggests that this pathogenic gut-brain circuit involves: (i) lipopolysaccharide (LPS) from the GI-tract resident enterotoxigenic Gram-negative bacteria Bacteroides fragilis (BF-LPS); (ii) LPS transit across the GI-tract barrier into the systemic circulation; (iii) transport of a highly pro-inflammatory systemic BF-LPS across the blood-brain barrier (BBB) into the brain-parenchyma and neuronal-cytoplasm; (iv) activation and signaling via the pro-inflammatory NF-kB (p50/p65) transcription-factor complex; (v) NF-kB-coupling and significant up-regulation of the inducible pro-inflammatory microRNA-146a (miRNA-146a) and microRNA-155 (miRNA-155); each containing multiple NF-kB DNA-binding and activation sites in their immediate promoters; and (vi) subsequent down-regulation of miRNA-146a-miRNA-155 regulated mRNA targets such as that encoding complement factor H (CFH), a soluble complement control glycoprotein and key repressor of the innate-immune response. Down-regulated CFH expression activates the complement-system, the major non-cellular component of the innate-immune system while propagating neuro-inflammation. Other GI-tract microbes and their highly complex pro-inflammatory exudates may contribute to this pathogenic GI-tract-brain pathway. We speculate that it may be significant that the first Gram-negative anaerobic bacterial species intensively studied as a potential contributor to the onset of Alzheimer’s disease (AD), that being the bacillus Bacteroides fragilis appears to utilize damaged or leaky physiological barriers and an activated NF-kB (p50-p65) – pro-inflammatory miRNA-146a-miRNA-155 signaling circuit to convey microbiome-derived pathogenic signals into the brain. alzheimer’s disease bacteroides fragilis (b. fragilis) complement factor h (cfh) dysbiosis microrna-146a microrna-155 nf-kb (p50/p65) Medicine R Yuhai Zhao verfasserin aut Wenhong Li verfasserin aut Walter Lukiw verfasserin aut In Folia Neuropathologica Termedia Publishing House, 2016 57(2019), 3, Seite 211-219 (DE-627)511229119 (DE-600)2233184-0 1509572X nnns volume:57 year:2019 number:3 pages:211-219 https://doi.org/10.5114/fn.2019.88449 kostenfrei https://doaj.org/article/77a16bc6e2ef4e82a02b4fd6906642d8 kostenfrei https://www.termedia.pl/Lipopolysaccharide-stimulated-NF-kB-miRNA-146a-and-miRNA-155-mediated-molecular-genetic-communication-between-the-human-gastrointestinal-tract-microbiome-and-the-brain,20,37898,1,1.html kostenfrei https://doaj.org/toc/1641-4640 Journal toc kostenfrei https://doaj.org/toc/1509-572X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 57 2019 3 211-219
allfieldsGer	10.5114/fn.2019.88449 doi (DE-627)DOAJ066505526 (DE-599)DOAJ77a16bc6e2ef4e82a02b4fd6906642d8 DE-627 ger DE-627 rakwb eng Peter Alexandrov verfasserin aut Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Through the use of RNA sequencing, microRNA (miRNA) and messenger RNA (mRNA) microfluidic array analysis, LED Northern, Western and ELISA analysis and multiple bioinformatics algorithms we have discovered a novel route for pathogenic communication between the human gastrointestinal (GI)-tract microbiome and the brain. The evidence suggests that this pathogenic gut-brain circuit involves: (i) lipopolysaccharide (LPS) from the GI-tract resident enterotoxigenic Gram-negative bacteria Bacteroides fragilis (BF-LPS); (ii) LPS transit across the GI-tract barrier into the systemic circulation; (iii) transport of a highly pro-inflammatory systemic BF-LPS across the blood-brain barrier (BBB) into the brain-parenchyma and neuronal-cytoplasm; (iv) activation and signaling via the pro-inflammatory NF-kB (p50/p65) transcription-factor complex; (v) NF-kB-coupling and significant up-regulation of the inducible pro-inflammatory microRNA-146a (miRNA-146a) and microRNA-155 (miRNA-155); each containing multiple NF-kB DNA-binding and activation sites in their immediate promoters; and (vi) subsequent down-regulation of miRNA-146a-miRNA-155 regulated mRNA targets such as that encoding complement factor H (CFH), a soluble complement control glycoprotein and key repressor of the innate-immune response. Down-regulated CFH expression activates the complement-system, the major non-cellular component of the innate-immune system while propagating neuro-inflammation. Other GI-tract microbes and their highly complex pro-inflammatory exudates may contribute to this pathogenic GI-tract-brain pathway. We speculate that it may be significant that the first Gram-negative anaerobic bacterial species intensively studied as a potential contributor to the onset of Alzheimer’s disease (AD), that being the bacillus Bacteroides fragilis appears to utilize damaged or leaky physiological barriers and an activated NF-kB (p50-p65) – pro-inflammatory miRNA-146a-miRNA-155 signaling circuit to convey microbiome-derived pathogenic signals into the brain. alzheimer’s disease bacteroides fragilis (b. fragilis) complement factor h (cfh) dysbiosis microrna-146a microrna-155 nf-kb (p50/p65) Medicine R Yuhai Zhao verfasserin aut Wenhong Li verfasserin aut Walter Lukiw verfasserin aut In Folia Neuropathologica Termedia Publishing House, 2016 57(2019), 3, Seite 211-219 (DE-627)511229119 (DE-600)2233184-0 1509572X nnns volume:57 year:2019 number:3 pages:211-219 https://doi.org/10.5114/fn.2019.88449 kostenfrei https://doaj.org/article/77a16bc6e2ef4e82a02b4fd6906642d8 kostenfrei https://www.termedia.pl/Lipopolysaccharide-stimulated-NF-kB-miRNA-146a-and-miRNA-155-mediated-molecular-genetic-communication-between-the-human-gastrointestinal-tract-microbiome-and-the-brain,20,37898,1,1.html kostenfrei https://doaj.org/toc/1641-4640 Journal toc kostenfrei https://doaj.org/toc/1509-572X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 57 2019 3 211-219
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language	English
source	In Folia Neuropathologica 57(2019), 3, Seite 211-219 volume:57 year:2019 number:3 pages:211-219
sourceStr	In Folia Neuropathologica 57(2019), 3, Seite 211-219 volume:57 year:2019 number:3 pages:211-219
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	alzheimer’s disease bacteroides fragilis (b. fragilis) complement factor h (cfh) dysbiosis microrna-146a microrna-155 nf-kb (p50/p65) Medicine R
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container_title	Folia Neuropathologica
authorswithroles_txt_mv	Peter Alexandrov @@aut@@ Yuhai Zhao @@aut@@ Wenhong Li @@aut@@ Walter Lukiw @@aut@@
publishDateDaySort_date	2019-01-01T00:00:00Z
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author	Peter Alexandrov
spellingShingle	Peter Alexandrov misc alzheimer’s disease misc bacteroides fragilis (b. fragilis) misc complement factor h (cfh) misc dysbiosis misc microrna-146a misc microrna-155 misc nf-kb (p50/p65) misc Medicine misc R Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain
authorStr	Peter Alexandrov
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topic_title	Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain alzheimer’s disease bacteroides fragilis (b. fragilis) complement factor h (cfh) dysbiosis microrna-146a microrna-155 nf-kb (p50/p65)
topic	misc alzheimer’s disease misc bacteroides fragilis (b. fragilis) misc complement factor h (cfh) misc dysbiosis misc microrna-146a misc microrna-155 misc nf-kb (p50/p65) misc Medicine misc R
topic_unstemmed	misc alzheimer’s disease misc bacteroides fragilis (b. fragilis) misc complement factor h (cfh) misc dysbiosis misc microrna-146a misc microrna-155 misc nf-kb (p50/p65) misc Medicine misc R
topic_browse	misc alzheimer’s disease misc bacteroides fragilis (b. fragilis) misc complement factor h (cfh) misc dysbiosis misc microrna-146a misc microrna-155 misc nf-kb (p50/p65) misc Medicine misc R
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title	Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain
ctrlnum	(DE-627)DOAJ066505526 (DE-599)DOAJ77a16bc6e2ef4e82a02b4fd6906642d8
title_full	Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain
author_sort	Peter Alexandrov
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author_browse	Peter Alexandrov Yuhai Zhao Wenhong Li Walter Lukiw
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doi_str_mv	10.5114/fn.2019.88449
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title_sort	lipopolysaccharide-stimulated, nf-kb-, mirna-146a- and mirna-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain
title_auth	Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain
abstract	Through the use of RNA sequencing, microRNA (miRNA) and messenger RNA (mRNA) microfluidic array analysis, LED Northern, Western and ELISA analysis and multiple bioinformatics algorithms we have discovered a novel route for pathogenic communication between the human gastrointestinal (GI)-tract microbiome and the brain. The evidence suggests that this pathogenic gut-brain circuit involves: (i) lipopolysaccharide (LPS) from the GI-tract resident enterotoxigenic Gram-negative bacteria Bacteroides fragilis (BF-LPS); (ii) LPS transit across the GI-tract barrier into the systemic circulation; (iii) transport of a highly pro-inflammatory systemic BF-LPS across the blood-brain barrier (BBB) into the brain-parenchyma and neuronal-cytoplasm; (iv) activation and signaling via the pro-inflammatory NF-kB (p50/p65) transcription-factor complex; (v) NF-kB-coupling and significant up-regulation of the inducible pro-inflammatory microRNA-146a (miRNA-146a) and microRNA-155 (miRNA-155); each containing multiple NF-kB DNA-binding and activation sites in their immediate promoters; and (vi) subsequent down-regulation of miRNA-146a-miRNA-155 regulated mRNA targets such as that encoding complement factor H (CFH), a soluble complement control glycoprotein and key repressor of the innate-immune response. Down-regulated CFH expression activates the complement-system, the major non-cellular component of the innate-immune system while propagating neuro-inflammation. Other GI-tract microbes and their highly complex pro-inflammatory exudates may contribute to this pathogenic GI-tract-brain pathway. We speculate that it may be significant that the first Gram-negative anaerobic bacterial species intensively studied as a potential contributor to the onset of Alzheimer’s disease (AD), that being the bacillus Bacteroides fragilis appears to utilize damaged or leaky physiological barriers and an activated NF-kB (p50-p65) – pro-inflammatory miRNA-146a-miRNA-155 signaling circuit to convey microbiome-derived pathogenic signals into the brain.
abstractGer	Through the use of RNA sequencing, microRNA (miRNA) and messenger RNA (mRNA) microfluidic array analysis, LED Northern, Western and ELISA analysis and multiple bioinformatics algorithms we have discovered a novel route for pathogenic communication between the human gastrointestinal (GI)-tract microbiome and the brain. The evidence suggests that this pathogenic gut-brain circuit involves: (i) lipopolysaccharide (LPS) from the GI-tract resident enterotoxigenic Gram-negative bacteria Bacteroides fragilis (BF-LPS); (ii) LPS transit across the GI-tract barrier into the systemic circulation; (iii) transport of a highly pro-inflammatory systemic BF-LPS across the blood-brain barrier (BBB) into the brain-parenchyma and neuronal-cytoplasm; (iv) activation and signaling via the pro-inflammatory NF-kB (p50/p65) transcription-factor complex; (v) NF-kB-coupling and significant up-regulation of the inducible pro-inflammatory microRNA-146a (miRNA-146a) and microRNA-155 (miRNA-155); each containing multiple NF-kB DNA-binding and activation sites in their immediate promoters; and (vi) subsequent down-regulation of miRNA-146a-miRNA-155 regulated mRNA targets such as that encoding complement factor H (CFH), a soluble complement control glycoprotein and key repressor of the innate-immune response. Down-regulated CFH expression activates the complement-system, the major non-cellular component of the innate-immune system while propagating neuro-inflammation. Other GI-tract microbes and their highly complex pro-inflammatory exudates may contribute to this pathogenic GI-tract-brain pathway. We speculate that it may be significant that the first Gram-negative anaerobic bacterial species intensively studied as a potential contributor to the onset of Alzheimer’s disease (AD), that being the bacillus Bacteroides fragilis appears to utilize damaged or leaky physiological barriers and an activated NF-kB (p50-p65) – pro-inflammatory miRNA-146a-miRNA-155 signaling circuit to convey microbiome-derived pathogenic signals into the brain.
abstract_unstemmed	Through the use of RNA sequencing, microRNA (miRNA) and messenger RNA (mRNA) microfluidic array analysis, LED Northern, Western and ELISA analysis and multiple bioinformatics algorithms we have discovered a novel route for pathogenic communication between the human gastrointestinal (GI)-tract microbiome and the brain. The evidence suggests that this pathogenic gut-brain circuit involves: (i) lipopolysaccharide (LPS) from the GI-tract resident enterotoxigenic Gram-negative bacteria Bacteroides fragilis (BF-LPS); (ii) LPS transit across the GI-tract barrier into the systemic circulation; (iii) transport of a highly pro-inflammatory systemic BF-LPS across the blood-brain barrier (BBB) into the brain-parenchyma and neuronal-cytoplasm; (iv) activation and signaling via the pro-inflammatory NF-kB (p50/p65) transcription-factor complex; (v) NF-kB-coupling and significant up-regulation of the inducible pro-inflammatory microRNA-146a (miRNA-146a) and microRNA-155 (miRNA-155); each containing multiple NF-kB DNA-binding and activation sites in their immediate promoters; and (vi) subsequent down-regulation of miRNA-146a-miRNA-155 regulated mRNA targets such as that encoding complement factor H (CFH), a soluble complement control glycoprotein and key repressor of the innate-immune response. Down-regulated CFH expression activates the complement-system, the major non-cellular component of the innate-immune system while propagating neuro-inflammation. Other GI-tract microbes and their highly complex pro-inflammatory exudates may contribute to this pathogenic GI-tract-brain pathway. We speculate that it may be significant that the first Gram-negative anaerobic bacterial species intensively studied as a potential contributor to the onset of Alzheimer’s disease (AD), that being the bacillus Bacteroides fragilis appears to utilize damaged or leaky physiological barriers and an activated NF-kB (p50-p65) – pro-inflammatory miRNA-146a-miRNA-155 signaling circuit to convey microbiome-derived pathogenic signals into the brain.
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title_short	Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain
url	https://doi.org/10.5114/fn.2019.88449 https://doaj.org/article/77a16bc6e2ef4e82a02b4fd6906642d8 https://www.termedia.pl/Lipopolysaccharide-stimulated-NF-kB-miRNA-146a-and-miRNA-155-mediated-molecular-genetic-communication-between-the-human-gastrointestinal-tract-microbiome-and-the-brain,20,37898,1,1.html https://doaj.org/toc/1641-4640 https://doaj.org/toc/1509-572X
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up_date	2024-07-03T20:25:45.019Z
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