Role of pregnane X-receptor in regulating bacterial translocation in chronic liver diseases

Mohandas, Sundhar; Vairappan, Balasubramaniyan

doi:10.4254/wjh.v9.i32.1210

Cited by 19 publications

(15 citation statements)

References 157 publications

(214 reference statements)

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“…Since PXR has been demonstrated to play an important role in protecting the barrier in intestinal or liver disease 17,23 , we investigated whether PXR also plays a role in NEC pathogenesis. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…As the MAPK pathway could affect tight junctions and cause dysfunction of the intestinal barrier 23,25,26 , we further examined whether PXR could regulate MAPK pathway signaling. After Caco-2 cells were treated with LPS at 5 μg/ml for 30 min, we observed increased phosphorylation of Erk and p38 and a notable increase in phospho-JNK levels (Fig.…”

Section: Pxr Could Inhibit the Phosphorylation Of Jnkmentioning

confidence: 99%

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Probiotics Mixture Reinforces Barrier Function to Ameliorate Necrotizing Enterocolitis by Regulating PXR-JNK Pathway

Zhao

Zhou

Liang

et al. 2020

Preprint

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Background: Intestinal dysbiosis is believed to be one of the factors inducing neonatal necrotizing enterocolitis (NEC). Probiotics have been employed to treat NEC in a number of animal experiments and clinical trials, and some significant benefits of utilizing probiotics for the prevention or alleviation of NEC have been confirmed. However, the mechanism underlying the efficacy of probiotics in treating NEC has not been elucidated. Results: Impairment of the intestinal barrier, which was characterized by the decreased expression of tight junction components, was observed in the pathogenesis of NEC. The probiotic mixture alleviated this intestinal damage by enhancing the function of the barrier. Meanwhile, the probiotics remodeled the composition of the intestinal microbiota in NEC mice. Furthermore, increased expression of the pregnane X receptor ( PXR ) was observed after treatment with the probiotic mixture, and PXR overexpression in Caco-2 cells protected the barrier from lipopolysaccharide (LPS) damage. Further research showed that PXR could inhibit the phosphorylation of c-Jun N-terminal kinase (JNK) and could increase the expression of tight junction components. Conclusions: Our study confirmed that probiotics could ameliorate intestinal lesions by enhancing the function of the mucosal barrier. Specifically, probiotics may target PXR, which may subsequently enhance the expression of tight junction components by inhibiting the phosphorylation of JNK and enhancing the function of the barrier.

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Section: Resultsmentioning

confidence: 99%

Section: Pxr Could Inhibit the Phosphorylation Of Jnkmentioning

confidence: 99%

Probiotics Mixture Reinforces Barrier Function to Ameliorate Necrotizing Enterocolitis by Regulating PXR-JNK Pathway

Zhao

Zhou

Liang

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Intestinal TJ proteins play an important function in maintaining gut barrier and in restricting bacterial translocation to the liver and the systemic circulation. 86,87 One study revealed elevated levels of circulating bacteria and bacterial endotoxins beta-glucan and lipopolysaccharide (LPS) in severely ill patients with SARS-CoV-2 infection. 88 The regulation of TJ proteins is facilitated through nuclear receptors such as Pregnane X receptor, whose activation was seen to confer preserved TJ proteins 87 and protect against bacterial translocation in cirrhosis.…”

Section: Disruption Of Tight Junction Protein a Potential Mechanismentioning

confidence: 99%

Severe acute respiratory syndrome coronavirus‐2 infection and the gut–liver axis

Mohandas

Vairappan

2020

J of Digest Diseases

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Patients affected by coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, manifest various gastrointestinal and hepatic abnormalities alongside respiratory disorders. The identification of this virus in the feces of more than 50% of infected individuals indicates the possibility of viral shedding and fecal-to-oral transmission. Preliminary reports have also identified alterations in the intestinal microbiota profile in infected individuals. Moreover, COVID-19 patients manifest various degrees of liver injury characterized by alterations in liver enzymes. Digestive symptoms and liver abnormalities correlate with disease severity, the incidence of critical outcomes and patient's recovery. However, the pathogenic mechanisms behind COVID-19-induced abnormalities in the gut-liver axis seem to be multifactorial in origin. This review compiles current knowledge sourced from preclinical and clinical research and summarizes gastrointestinal and hepatic dysfunctions observed following SARS-CoV-2 infection, and also explores the possible mechanisms generating abnormalities in the gut-liver axis. Furthermore, this review sheds light on possible therapeutic targets against these disorders.

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“…As the MAPK pathway could affect tight junctions and cause dysfunction of the intestinal barrier 23,25,26 , we further examined whether PXR could regulate MAPK pathway signaling. After Caco-2 cells were treated with LPS at 5 µg/ml for 30 min, we observed increased phosphorylation of Erk and p38 and a notable increase in phospho-JNK levels (Fig.…”

Section: Activation Of Pxr Improved Barrier Function In Caco-2 Cellsmentioning

confidence: 99%

Probiotics Mixture Reinforces Barrier Function to Ameliorate Necrotizing Enterocolitis by Regulating PXR-JNK Pathway

Zhao

Zhou

Liang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Intestinal dysbiosis is believed to be one of the factors inducing neonatal necrotizing enterocolitis (NEC). Probiotics have been employed to treat NEC in a number of animal experiments and clinical trials, and some significant benefits of utilizing probiotics for the prevention or alleviation of NEC have been confirmed. However, the mechanism underlying the efficacy of probiotics in treating NEC has not been elucidated.Results: Impairment of the intestinal barrier, which was characterized by the decreased expression of tight junction components, was observed in the pathogenesis of NEC. The probiotic mixture alleviated this intestinal damage by enhancing the function of the barrier. Meanwhile, the probiotics remodeled the composition of the intestinal microbiota in NEC mice. Furthermore, increased expression of the pregnane X receptor (PXR) was observed after treatment with the probiotic mixture, and PXR overexpression in Caco-2 cells protected the barrier from lipopolysaccharide (LPS) damage. Further research showed that PXR could inhibit the phosphorylation of c-Jun N-terminal kinase (JNK) and could increase the expression of tight junction components.Conclusions: Our study confirmed that probiotics could ameliorate intestinal lesions by enhancing the function of the mucosal barrier. Specifically, probiotics may target PXR, which may subsequently enhance the expression of tight junction components by inhibiting the phosphorylation of JNK and enhancing the function of the barrier.

show abstract

Role of pregnane X-receptor in regulating bacterial translocation in chronic liver diseases

Cited by 19 publications

References 157 publications

Probiotics Mixture Reinforces Barrier Function to Ameliorate Necrotizing Enterocolitis by Regulating PXR-JNK Pathway

Probiotics Mixture Reinforces Barrier Function to Ameliorate Necrotizing Enterocolitis by Regulating PXR-JNK Pathway

Severe acute respiratory syndrome coronavirus‐2 infection and the gut–liver axis

Probiotics Mixture Reinforces Barrier Function to Ameliorate Necrotizing Enterocolitis by Regulating PXR-JNK Pathway

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