Correlation of spatio-temporal characteristics of intestinal inflammation with IL-17 in a rat model of hypoganglionosis

Yu, Hui; Cao, Ningjia; Pan, Weikang; Su, Li; Zhao, Yuying; Tian, Donghao; Xu, Wenyao; Gao, Ya; Zheng, Bin

doi:10.1016/j.bbrc.2018.10.129

Cited by 3 publications

(4 citation statements)

References 22 publications

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“…The negative effect of the hypoganglionosis intestinal microenvironment on ENCCs may be due to various factors, including microbiota, metabolites, inflammation, toxins or remnants from epithelial cells (Pierre et al , 2014; Venkataramana et al , 2015; Li et al , 2016; Neuvonen et al , 2018; Yu et al , 2018).…”

Section: Resultsmentioning

confidence: 99%

“…However, ENCC engraftment in hypoganglionic gut encounters interference from shifted microbial populations and intestinal inflammation. These obstacles may generate adverse effects on neurons, so they require further characterization before targeting in the clinical application (Venkataramana et al , 2015; Neuvonen et al , 2018; Yu et al , 2018). This study revealed that FMT reduced the harmful effects of hypoganglionic intestine on ENCC transplantation and improved intestinal function in a hypoganglionosis rat model.…”

Section: Discussionmentioning

confidence: 99%

“…The immune system and microbiota have been proposed to impact the ENCC phenotype and development, and the organization and maturation of the ENS (Yoo & Mazmanian, 2017; Yarandi et al , 2020). Thus, the abnormalities present in HSCR, including intestinal inflammation, microbiota disorders, and metabolite imbalance, may create a hostile environment that leads to incompatibility between ENCCs and the intestinal microenvironment (Neuvonen et al , 2018; Yu et al , 2018). Although intestinal inflammation has been shown to be selectively cytotoxic to neurons, its effects on ENCCs are still unclear (Venkataramana et al , 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Emerging research have suggested dysbiosis and inflamed intestines in HSCR, which may interfere with ENCCs (Pierre et al , 2014; Venkataramana et al , 2015; Li et al , 2016; Neuvonen et al , 2018; Yu et al , 2018). Fecal microbiota transplantation (FMT) seems an effective therapeutic option for inflamed bowel diseases as it can reshape a recipient's gut microbiome (El‐Salhy et al , 2020; Quraishi et al , 2020).…”

Section: Introductionmentioning

confidence: 99%

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Fecal microbiota transplantation enhances cell therapy in a rat model of hypoganglionosis by SCFA‐induced MEK1/2 signaling pathway

Tian

Pan

et al. 2022

The EMBO Journal

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Hirschsprung disease (HSCR), one of several neurocristopathies in children, is characterized by nerve loss in the large intestine and is mainly treated by surgery, which causes severe complications. Enteric neural crest-derived cell (ENCC) transplantation is a potential therapeutic strategy; however, so far with poor efficacy. Here, we assessed whether and how fecal microbiota transplantation (FMT) could improve ENCC transplantation in a rat model of hypoganglionosis; a condition similar to HSCR, with less intestinal innervation. We found that the hypoganglionosis intestinal microenvironment negatively influenced the ENCC functional phenotype in vitro and in vivo. Combining 16S rDNA sequencing and targeted mass spectrometry revealed microbial dysbiosis and reduced short-chain fatty acid (SCFA) production in the hypoganglionic gut. FMT increased the abundance of Bacteroides and Clostridium, SCFA production, and improved outcomes following ENCC transplantation. SCFAs alone stimulated ENCC proliferation, migration, and supported ENCC transplantation. Transcriptomewide mRNA sequencing identified MAPK signaling as the top differentially regulated pathway in response to SCFA exposure, and inhibition of MEK1/2 signaling abrogated the SCFA-mediated effects on ENCC. This study demonstrates that FMT improves cell therapy for hypoganglionosis via short-chain fatty acid metabolisminduced MEK1/2 signaling.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Fecal microbiota transplantation enhances cell therapy in a rat model of hypoganglionosis by SCFA‐induced MEK1/2 signaling pathway

Tian

Pan

et al. 2022

The EMBO Journal

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Total flavonoids from Tetrastigma hemsleyanum ameliorates inflammatory stress in concanavalin A-induced autoimmune hepatitis mice by regulating Treg/Th17 immune homeostasis

Peng

Lou

et al. 2019

Inflammopharmacol

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Targeting Enteric Neurons and Plexitis for the Management of Inflammatory Bowel Disease

Stavely

Abalo

Nurgali

2020

CDT

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: Ulcerative colitis (UC) and Crohn’s disease (CD) are pathological conditions with an unknown aetiology that are characterised by severe inflammation of the intestinal tract and collectively referred to as inflammatory bowel disease (IBD). Current treatments are mostly ineffective due to their limited efficacy or toxicity necessitating surgical resection of the affected bowel. The management of IBD is hindered by a lack of prognostic markers for clinical inflammatory relapse. Intestinal inflammation associates with the infiltration of immune cells (leukocytes) into, or surrounding, the neuronal ganglia of the enteric nervous system (ENS) termed plexitis or ganglionitis. Histological observation of plexitis in unaffected intestinal regions is emerging as a vital predictive marker for IBD relapses. Plexitis associates with alterations to structure, cellular composition, molecular expression and electrophysiological function of enteric neurons. Moreover, plexitis often occurs before the onset of gross clinical inflammation which may indicate that plexitis can contribute to the progression of intestinal inflammation. In this review, the bilateral relationships between the ENS and inflammation are discussed. This includes the effects and mechanisms of inflammation-induced enteric neuronal loss and plasticity. Additionally, the role of enteric neurons in preventing antigenic/pathogenic insult and immunomodulation is explored. While all current treatments target the inflammatory pathology of IBD, interventions that protect the ENS may offer an alternative avenue for therapeutic intervention.

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Correlation of spatio-temporal characteristics of intestinal inflammation with IL-17 in a rat model of hypoganglionosis

Cited by 3 publications

References 22 publications

Fecal microbiota transplantation enhances cell therapy in a rat model of hypoganglionosis by SCFA‐induced MEK1/2 signaling pathway

Fecal microbiota transplantation enhances cell therapy in a rat model of hypoganglionosis by SCFA‐induced MEK1/2 signaling pathway

Total flavonoids from Tetrastigma hemsleyanum ameliorates inflammatory stress in concanavalin A-induced autoimmune hepatitis mice by regulating Treg/Th17 immune homeostasis

Targeting Enteric Neurons and Plexitis for the Management of Inflammatory Bowel Disease

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