O070 : CX3CR1 is a gatekeeper for intestinal barrier integrity: Limiting steatohepatitis by promoting intestinal homeostasis

Schneider, KM; Bieghs, Veerle; Heymann, Felix; Hu, Wei Shou; Liao, Lijun; Gaßler, Nikolaus; Pabst, Oliver; Latz, Eicke; Sellge, Gernot; Penders, John; Tacke, Frank

doi:10.1016/s0168-8278(15)30084-2

Cited by 2 publications

(1 citation statement)

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“…Under inflammatory conditions, monocyte- derived CCR2 + CX3CR1 + MΦ infiltrate the gut mucosa and prime Th17 cell responses 43, 47 . At steady state, CX3CR1 + MΦ are indispensable for epithelial integrity, control of bacterial translocation, and development of oral and commensal tolerance by secreting anti-inflammatory cytokines and maintaining Treg 44, 68 . CX3CR1 MΦ further promote intestinal homeostasis by microbiota-dependent crosstalk with IL-22-secreting ILC3 85 .…”

Section: Discussionmentioning

confidence: 99%

Lack of mucosal cholinergic innervation is associated with increased risk of enterocolitis in Hirschsprung’s disease

Keck

Galati-Fournier

Kym

et al. 2020

Preprint

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Background & AimsHirschsprung’s disease (HSCR) is a congenital intestinal motility disorder defined by the absence of enteric nervous cells (ganglia). The development of HSCR-associated enterocolitis remains a life-threatening complication. Absence of enteric ganglia implicates extramural innervation of acetylcholine-secreting (cholinergic) nerve fibers. Cholinergic signals have been reported to control excessive inflammation, but the impact on HSCR-associated enterocolitis is unknown.MethodsWe enrolled 44 HSCR patients in a prospective multicenter study and grouped them according to their degree of colonic mucosal cholinergic innervation using immunohistochemistry. The fiber phenotype was correlated with the tissue cytokine profile as well as immune cell frequencies using quantitative reverse-transcribed real-time polymerase chain reaction (qRT-PCR) of whole colonic tissue and fluorescence-activated cell sorting (FACS) analysis of isolated colonic immune cells. Fiber-associated immune cells were identified using confocal immunofluorescence microscopy and characterized by RNA-seq analysis. Microbial dysbiosis was analyzed in colonic patient tissue using 16S rDNA gene sequencing. Finally, the fiber phenotype was correlated with postoperative enterocolitis manifestation.ResultsWe provided evidence that extrinsic mucosal innervation correlated with reduced interleukin (IL)-17 cytokine levels and T-helper-17 (Th17) cell frequencies. Bipolar CD14high macrophages colocalized with neurons and expressed significantly less interleukin-23, a Th17-promoting cytokine. HSCR patients lacking mucosal cholinergic nerve fibers showed microbial dysbiosis and had a higher incidence of postoperative enterocolitis.ConclusionThe mucosal fiber phenotype might serve as a new prognostic marker for enterocolitis development in HSCR patients and may offer an approach to personalized patient care and new future therapeutic options. (www.clinicaltrials.gov accessing number NCT03617640)

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Section: Discussionmentioning

confidence: 99%

Lack of mucosal cholinergic innervation is associated with increased risk of enterocolitis in Hirschsprung’s disease

Keck

Galati-Fournier

Kym

et al. 2020

Preprint

View full text Add to dashboard Cite

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Age-Related NAFLD: The Use of Probiotics as a Supportive Therapeutic Intervention

Campagnoli

Marchesi

Vairetti

et al. 2022

Cells

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Human aging, a natural process characterized by structural and physiological changes, leads to alterations of homeostatic mechanisms, decline of biological functions, and subsequently, the organism becomes vulnerable to external stress or damage. In fact, the elderly population is prone to develop diseases due to deterioration of physiological and biological systems. With aging, the production of reactive oxygen species (ROS) increases, and this causes lipid, protein, and DNA damage, leading to cellular dysfunction and altered cellular processes. Indeed, oxidative stress plays a key role in the pathogenesis of several chronic disorders, including hepatic diseases, such as non-alcoholic fatty liver disease (NAFLD). NAFLD, the most common liver disorder in the Western world, is characterized by intrahepatic lipid accumulation; is highly prevalent in the aging population; and is closely associated with obesity, insulin resistance, hypertension, and dyslipidemia. Among the risk factors involved in the pathogenesis of NAFLD, the dysbiotic gut microbiota plays an essential role, leading to low-grade chronic inflammation, oxidative stress, and production of various toxic metabolites. The intestinal microbiota is a dynamic ecosystem of microbes involved in the maintenance of physiological homeostasis; the alteration of its composition and function, during aging, is implicated in different liver diseases. Therefore, gut microbiota restoration might be a complementary approach for treating NAFLD. The administration of probiotics, which can relieve oxidative stress and elicit several anti-aging properties, could be a strategy to modify the composition and restore a healthy gut microbiota. Indeed, probiotics could represent a valid supplement to prevent and/or help treating some diseases, such as NAFLD, thus improving the already available pharmacological intervention. Moreover, in aging, intervention of prebiotics and fecal microbiota transplantation, as well as probiotics, will provide novel therapeutic approaches. However, the relevant research is limited, and several scientific research works need to be done in the near future to confirm their efficacy.

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O070 : CX3CR1 is a gatekeeper for intestinal barrier integrity: Limiting steatohepatitis by promoting intestinal homeostasis

Cited by 2 publications

References 0 publications

Lack of mucosal cholinergic innervation is associated with increased risk of enterocolitis in Hirschsprung’s disease

Lack of mucosal cholinergic innervation is associated with increased risk of enterocolitis in Hirschsprung’s disease

Age-Related NAFLD: The Use of Probiotics as a Supportive Therapeutic Intervention

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