The Experts below are selected from a list of 26541 Experts worldwide ranked by ideXlab platform
Kenneth W Simpson - One of the best experts on this subject based on the ideXlab platform.
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inflammation drives Dysbiosis and bacterial invasion in murine models of ileal crohn s disease
PLOS ONE, 2012Co-Authors: Melanie Craven, Belgin Dogan, Ellen J Scherl, Scot E. Dowd, Charlotte E Egan, Eric Y Denkers, Sean P Mcdonough, Dwight D Bowman, Kenneth W SimpsonAbstract:Background and Aims: Understanding the interplay between genetic susceptibility, the microbiome, the environment and the immune system in Crohn’s Disease (CD) is essential for developing optimal therapeutic strategies. We sought to examine the dynamics of the relationship between inflammation, the ileal microbiome, and host genetics in murine models of ileitis. Methods: We induced ileal inflammation of graded severity in C57BL6 mice by gavage with Toxoplasma gondii, Giardia muris, low dose indomethacin (LDI;0.1 mg/mouse), or high dose indomethacin (HDI;1 mg/mouse). The composition and spatial distribution of the mucosal microbiome was evaluated by 16S rDNA pyrosequencing and fluorescence in situ hybridization. Mucosal E. coli were enumerated by quantitative PCR, and characterized by phylogroup, genotype and pathotype. Results: Moderate to severe ileitis induced by T. gondii (day 8) and HDI caused a consistent shift from .95% Gram + Firmicutes to .95% Gram - Proteobacteria. This was accompanied by reduced microbial diversity and mucosal invasion by adherent and invasive E. coli, mirroring the Dysbiosis of ileal CD. In contrast, Dysbiosis and bacterial invasion did not develop in mice with mild ileitis induced by Giardia muris. Superimposition of genetic susceptibility and T. Gondii infection revealed greatest Dysbiosis and bacterial invasion in the CD-susceptible genotype, NOD2 2/2 , and reduced Dysbiosis in ileitis-resistant CCR2 2/2 mice. Abrogating inflammation with the CD therapeutic anti-TNF-a-mAb tempered Dysbiosis and bacterial invasion. Conclusions: Acute ileitis induces Dysbiosis and proliferation of mucosally invasive E. coli, irrespective of trigger and genotype. The identification of CCR2 as a target for therapeutic intervention, and discovery that host genotype and therapeutic blockade of inflammation impact the threshold and extent of ileal Dysbiosis are of high relevance to developing effective therapies for CD.
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Inflammation drives Dysbiosis and bacterial invasion in murine models of ileal Crohn's Disease
PLoS ONE, 2012Co-Authors: Melanie Craven, Dwight Bowman, Belgin Dogan, Ellen J Scherl, Scot E. Dowd, Charlotte E Egan, Eric Y Denkers, Sean P Mcdonough, Kenneth W SimpsonAbstract:BACKGROUND AND AIMS: Understanding the interplay between genetic susceptibility, the microbiome, the environment and the immune system in Crohn's Disease (CD) is essential for developing optimal therapeutic strategies. We sought to examine the dynamics of the relationship between inflammation, the ileal microbiome, and host genetics in murine models of ileitis.\n\nMETHODS: We induced ileal inflammation of graded severity in C57BL6 mice by gavage with Toxoplasma gondii, Giardia muris, low dose indomethacin (LDI; 0.1 mg/mouse), or high dose indomethacin (HDI; 1 mg/mouse). The composition and spatial distribution of the mucosal microbiome was evaluated by 16S rDNA pyrosequencing and fluorescence in situ hybridization. Mucosal E. coli were enumerated by quantitative PCR, and characterized by phylogroup, genotype and pathotype.\n\nRESULTS: Moderate to severe ileitis induced by T. gondii (day 8) and HDI caused a consistent shift from >95% gram + Firmicutes to >95% gram - Proteobacteria. This was accompanied by reduced microbial diversity and mucosal invasion by adherent and invasive E. coli, mirroring the Dysbiosis of ileal CD. In contrast, Dysbiosis and bacterial invasion did not develop in mice with mild ileitis induced by Giardia muris. Superimposition of genetic susceptibility and T. Gondii infection revealed greatest Dysbiosis and bacterial invasion in the CD-susceptible genotype, NOD2(-/-), and reduced Dysbiosis in ileitis-resistant CCR2(-/-) mice. Abrogating inflammation with the CD therapeutic anti-TNF-α-mAb tempered Dysbiosis and bacterial invasion.\n\nCONCLUSIONS: Acute ileitis induces Dysbiosis and proliferation of mucosally invasive E. coli, irrespective of trigger and genotype. The identification of CCR2 as a target for therapeutic intervention, and discovery that host genotype and therapeutic blockade of inflammation impact the threshold and extent of ileal Dysbiosis are of high relevance to developing effective therapies for CD.
Ardythe L Morrow - One of the best experts on this subject based on the ideXlab platform.
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early microbial and metabolomic signatures predict later onset of necrotizing enterocolitis in preterm infants
Microbiome, 2013Co-Authors: Ardythe L Morrow, Anne J Lagomarcino, Kurt Schibler, Diana H Taft, Zhuoteng Yu, Bo Wang, Mekibib Altaye, Michael WagnerAbstract:Background: Necrotizing enterocolitis (NEC) is a devastating intestinal disease that afflicts 10% of extremely preterm infants. The contribution of early intestinal colonization to NEC onset is not understood, and predictive biomarkers to guide prevention are lacking. We analyzed banked stool and urine samples collected prior to disease onset from infants 99% versus 99% versus 38% in the other NEC cases and 84% in controls, P = 0.01). NEC preceded by Firmicutes Dysbiosis occurred earlier (onset, days 7 to 21) than NEC preceded by Proteobacteria Dysbiosis (onset, days 19 to 39). All NEC cases lacked Propionibacterium and were preceded by either Firmicutes (≥98% relative abundance, days 4 to 9) or Proteobacteria (≥90% relative abundance, days 10 to 16) Dysbiosis, while only 25% of controls had this phenotype (predictive value 88%, P = 0.001). Analysis of days 4 to 9 urine samples found no metabolites associated with all NEC cases, but alanine was positively associated with NEC cases that were preceded by Firmicutes Dysbiosis (P < 0.001) and histidine was inversely associated with NEC cases preceded by Proteobacteria Dysbiosis (P = 0.013). A high urinary alanine:histidine ratio was associated with microbial characteristics (P < 0.001) and provided good prediction of overall NEC (predictive value 78%, P =0 .007). Conclusions: Early Dysbiosis is strongly involved in the pathobiology of NEC. These striking findings require validation in larger studies but indicate that early microbial and metabolomic signatures may provide highly predictive biomarkers of NEC.
Josephine Ni - One of the best experts on this subject based on the ideXlab platform.
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A role for bacterial urease in gut Dysbiosis and Crohn’s disease
Science Translational Medicine, 2017Co-Authors: Josephine Ni, Tingchin David Shen, Eric Z Chen, Kyle Bittinger, Aubrey Bailey, Manuela Roggiani, Elliot S Friedman, Alexandra Sirota-madi, Lillian ChauAbstract:Gut Dysbiosis during inflammatory bowel disease involves alterations in the gut microbiota associated with inflammation of the host gut. We used a combination of shotgun metagenomic sequencing and metabolomics to analyze fecal samples from pediatric patients with Crohn’s disease and found an association between disease severity, gut Dysbiosis, and bacterial production of free amino acids. Nitrogen flux studies using 15 N in mice showed that activity of bacterial urease, an enzyme that releases ammonia by hydrolysis of host urea, led to the transfer of murine host-derived nitrogen to the gut microbiota where it was used for amino acid synthesis. Inoculation of a conventional murine host (pretreated with antibiotics and polyethylene glycol) with commensal Escherichia coli engineered to express urease led to Dysbiosis of the gut microbiota, resulting in a predominance of Proteobacteria species. This was associated with a worsening of immune-mediated colitis in these animals. A potential role for altered urease expression and nitrogen flux in the development of gut Dysbiosis suggests that bacterial urease may be a potential therapeutic target for inflammatory bowel diseases.
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a role for bacterial urease in gut Dysbiosis and crohn s disease
Science Translational Medicine, 2017Co-Authors: Josephine Ni, Tingchin David Shen, Eric Z Chen, Kyle Bittinger, Aubrey Bailey, Manuela Roggiani, Alexandra Sirotamadi, Elliot S Friedman, Lillian Chau, Ilana NissimAbstract:Gut Dysbiosis during inflammatory bowel disease involves alterations in the gut microbiota associated with inflammation of the host gut. We used a combination of shotgun metagenomic sequencing and metabolomics to analyze fecal samples from pediatric patients with Crohn’s disease and found an association between disease severity, gut Dysbiosis, and bacterial production of free amino acids. Nitrogen flux studies using 15 N in mice showed that activity of bacterial urease, an enzyme that releases ammonia by hydrolysis of host urea, led to the transfer of murine host-derived nitrogen to the gut microbiota where it was used for amino acid synthesis. Inoculation of a conventional murine host (pretreated with antibiotics and polyethylene glycol) with commensal Escherichia coli engineered to express urease led to Dysbiosis of the gut microbiota, resulting in a predominance of Proteobacteria species. This was associated with a worsening of immune-mediated colitis in these animals. A potential role for altered urease expression and nitrogen flux in the development of gut Dysbiosis suggests that bacterial urease may be a potential therapeutic target for inflammatory bowel diseases.
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Gut microbiota and IBD: causation or correlation?
Nature Reviews Gastroenterology & Hepatology, 2017Co-Authors: Josephine Ni, Gary D. Wu, Lindsey Albenberg, Vesselin T. TomovAbstract:Alterations in intestinal microbial composition have long been associated with chronic inflammation; however, a definitive cause–effect relationship between Dysbiosis and IBD has been difficult to prove, especially in humans Dysbiosis alters not only the composition of the intestinal microbiota, but also its metabolome, thereby exerting a wide range of effects on the host While the microbiota plays a key pathogenic role in IBD, chronic inflammation, in turn, promotes Dysbiosis by altering the oxidative and metabolic environment of the gut Animal studies have elucidated key immunological pathways in the pathogenesis of IBD, established both pro-inflammatory and anti-inflammatory roles of the gut microbiota, and shown that the gut microbiota is indispensable for pathogenesis in most colitis models Microbial-based treatments will likely have a role in the future management of IBD; however, many questions remain regarding the bacterial composition, timing of administration, and patient selection for such therapies A general consensus exists that IBD is associated with compositional and metabolic changes in the intestinal microbiota (Dysbiosis). However, a direct causal relationship between Dysbiosis and IBD has not been definitively established in humans. Findings from animal models have revealed diverse and context-specific roles of the gut microbiota in health and disease, ranging from protective to pro-inflammatory actions. Moreover, evidence from these experimental models suggest that although gut bacteria often drive immune activation, chronic inflammation in turn shapes the gut microbiota and contributes to Dysbiosis. The purpose of this Review is to summarize current associations between IBD and Dysbiosis, describe the role of the gut microbiota in the context of specific animal models of colitis, and discuss the potential role of microbiota-focused interventions in the treatment of human IBD. Ultimately, more studies will be needed to define host–microbial relationships relevant to human disease and amenable to therapeutic interventions. Changes in the composition and metabolic function of the gut microbiota have been linked to IBD, but a direct causal association has yet to be established in humans. This Review discusses the evidence supporting Dysbiosis in the gut microbiota in Crohn's disease and ulcerative colitis, exploring evidence from animal models and the translation to human disease.
Michael Wagner - One of the best experts on this subject based on the ideXlab platform.
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early microbial and metabolomic signatures predict later onset of necrotizing enterocolitis in preterm infants
Microbiome, 2013Co-Authors: Ardythe L Morrow, Anne J Lagomarcino, Kurt Schibler, Diana H Taft, Zhuoteng Yu, Bo Wang, Mekibib Altaye, Michael WagnerAbstract:Background: Necrotizing enterocolitis (NEC) is a devastating intestinal disease that afflicts 10% of extremely preterm infants. The contribution of early intestinal colonization to NEC onset is not understood, and predictive biomarkers to guide prevention are lacking. We analyzed banked stool and urine samples collected prior to disease onset from infants 99% versus 99% versus 38% in the other NEC cases and 84% in controls, P = 0.01). NEC preceded by Firmicutes Dysbiosis occurred earlier (onset, days 7 to 21) than NEC preceded by Proteobacteria Dysbiosis (onset, days 19 to 39). All NEC cases lacked Propionibacterium and were preceded by either Firmicutes (≥98% relative abundance, days 4 to 9) or Proteobacteria (≥90% relative abundance, days 10 to 16) Dysbiosis, while only 25% of controls had this phenotype (predictive value 88%, P = 0.001). Analysis of days 4 to 9 urine samples found no metabolites associated with all NEC cases, but alanine was positively associated with NEC cases that were preceded by Firmicutes Dysbiosis (P < 0.001) and histidine was inversely associated with NEC cases preceded by Proteobacteria Dysbiosis (P = 0.013). A high urinary alanine:histidine ratio was associated with microbial characteristics (P < 0.001) and provided good prediction of overall NEC (predictive value 78%, P =0 .007). Conclusions: Early Dysbiosis is strongly involved in the pathobiology of NEC. These striking findings require validation in larger studies but indicate that early microbial and metabolomic signatures may provide highly predictive biomarkers of NEC.
Melanie Craven - One of the best experts on this subject based on the ideXlab platform.
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inflammation drives Dysbiosis and bacterial invasion in murine models of ileal crohn s disease
PLOS ONE, 2012Co-Authors: Melanie Craven, Belgin Dogan, Ellen J Scherl, Scot E. Dowd, Charlotte E Egan, Eric Y Denkers, Sean P Mcdonough, Dwight D Bowman, Kenneth W SimpsonAbstract:Background and Aims: Understanding the interplay between genetic susceptibility, the microbiome, the environment and the immune system in Crohn’s Disease (CD) is essential for developing optimal therapeutic strategies. We sought to examine the dynamics of the relationship between inflammation, the ileal microbiome, and host genetics in murine models of ileitis. Methods: We induced ileal inflammation of graded severity in C57BL6 mice by gavage with Toxoplasma gondii, Giardia muris, low dose indomethacin (LDI;0.1 mg/mouse), or high dose indomethacin (HDI;1 mg/mouse). The composition and spatial distribution of the mucosal microbiome was evaluated by 16S rDNA pyrosequencing and fluorescence in situ hybridization. Mucosal E. coli were enumerated by quantitative PCR, and characterized by phylogroup, genotype and pathotype. Results: Moderate to severe ileitis induced by T. gondii (day 8) and HDI caused a consistent shift from .95% Gram + Firmicutes to .95% Gram - Proteobacteria. This was accompanied by reduced microbial diversity and mucosal invasion by adherent and invasive E. coli, mirroring the Dysbiosis of ileal CD. In contrast, Dysbiosis and bacterial invasion did not develop in mice with mild ileitis induced by Giardia muris. Superimposition of genetic susceptibility and T. Gondii infection revealed greatest Dysbiosis and bacterial invasion in the CD-susceptible genotype, NOD2 2/2 , and reduced Dysbiosis in ileitis-resistant CCR2 2/2 mice. Abrogating inflammation with the CD therapeutic anti-TNF-a-mAb tempered Dysbiosis and bacterial invasion. Conclusions: Acute ileitis induces Dysbiosis and proliferation of mucosally invasive E. coli, irrespective of trigger and genotype. The identification of CCR2 as a target for therapeutic intervention, and discovery that host genotype and therapeutic blockade of inflammation impact the threshold and extent of ileal Dysbiosis are of high relevance to developing effective therapies for CD.
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Inflammation drives Dysbiosis and bacterial invasion in murine models of ileal Crohn's Disease
PLoS ONE, 2012Co-Authors: Melanie Craven, Dwight Bowman, Belgin Dogan, Ellen J Scherl, Scot E. Dowd, Charlotte E Egan, Eric Y Denkers, Sean P Mcdonough, Kenneth W SimpsonAbstract:BACKGROUND AND AIMS: Understanding the interplay between genetic susceptibility, the microbiome, the environment and the immune system in Crohn's Disease (CD) is essential for developing optimal therapeutic strategies. We sought to examine the dynamics of the relationship between inflammation, the ileal microbiome, and host genetics in murine models of ileitis.\n\nMETHODS: We induced ileal inflammation of graded severity in C57BL6 mice by gavage with Toxoplasma gondii, Giardia muris, low dose indomethacin (LDI; 0.1 mg/mouse), or high dose indomethacin (HDI; 1 mg/mouse). The composition and spatial distribution of the mucosal microbiome was evaluated by 16S rDNA pyrosequencing and fluorescence in situ hybridization. Mucosal E. coli were enumerated by quantitative PCR, and characterized by phylogroup, genotype and pathotype.\n\nRESULTS: Moderate to severe ileitis induced by T. gondii (day 8) and HDI caused a consistent shift from >95% gram + Firmicutes to >95% gram - Proteobacteria. This was accompanied by reduced microbial diversity and mucosal invasion by adherent and invasive E. coli, mirroring the Dysbiosis of ileal CD. In contrast, Dysbiosis and bacterial invasion did not develop in mice with mild ileitis induced by Giardia muris. Superimposition of genetic susceptibility and T. Gondii infection revealed greatest Dysbiosis and bacterial invasion in the CD-susceptible genotype, NOD2(-/-), and reduced Dysbiosis in ileitis-resistant CCR2(-/-) mice. Abrogating inflammation with the CD therapeutic anti-TNF-α-mAb tempered Dysbiosis and bacterial invasion.\n\nCONCLUSIONS: Acute ileitis induces Dysbiosis and proliferation of mucosally invasive E. coli, irrespective of trigger and genotype. The identification of CCR2 as a target for therapeutic intervention, and discovery that host genotype and therapeutic blockade of inflammation impact the threshold and extent of ileal Dysbiosis are of high relevance to developing effective therapies for CD.