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Involvement of toll-like receptor 5 in mouse model of colonic hypersensitivity induced by neonatal maternal separation

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World Journal of Gastroenterology 2022年第29期28卷 3903-3916页

作者： Geoffroy Mallaret Amandine Lashermes Mathieu Meleine Ludivine Boudieu Julie Barbier Youssef Aissouni Agathe Gelot Benoit Chassaing Andrew T Gewirtz Denis Ardid frederic Antonio carvalho Department of Pharmacology UMR 1107 NeuroDolUniversity of Clermont AuvergneClermont-Ferrand 63000France Department of Microbiology UniversitéParis-SaclayNational Research Institute for AgricultureFood and the EnvironmentAgroParisTechMicalis InstituteJouy-en-Josas 78350France Team“Mucosal Microbiota in Chronic Inflammatory Diseases” INSERM U1016CNRS UMR 8104UniversitéParis CitéParis 75014France Center for Inflammation Institute for Biomedical SciencesGeorgia State UniversityAtlantaGA30033United States Department of Pharmacology INSERM 1107 NeuroDOL/University of Clermont AuvergneClermont-Ferrand 63000France

BACKGROUND Chronic abdominal pain is the most common cause for gastroenterology consultation and is frequently associated with functional gastrointestinal disorders including irritable bowel syndrome and inflammatory bowel disease. These disorders present similar brain/gut/microbiota trialogue alterations, associated with abnormal intestinal permeability, intestinal dysbiosis and colonic hypersensitivity(CHS). Intestinal dysbiosis can alter colon homeostasis leading to abnormal activation of the innate immunity that promotes CHS, perhaps involving the toll-like receptors(TLRs), which play a central role in innate *** To understand the mechanisms between early life event paradigm on intestinal permeability, fecal microbiota composition and CHS development in mice with TLRs expression in *** Maternal separation model(NMS) CHS model, which mimics deleterious events in childhood that can induce a wide range of chronic disorders during adulthood were used. Colonic sensitivity of NMS mice was evaluated by colorectal distension(CRD) coupled with intracolonic pressure variation(IPV) measurement. Fecal microbiota composition was analyzed by 16S rRNA sequencing from weaning to CRD periods. TLR mRNA expression was evaluated in ***, the effect of acute intrarectal instillation of the TLR5 agonist flagellin(FliC) on CHS in adult naive wildtype mice was *** Around 50% of NMS mice exhibited increased intestinal permeability and CHS associated with intestinal dysbiosis, characterized by a significant decrease of species richness, an alteration of the core fecal microbiota and a specific increased relative abundance of flagellated bacteria. Only TLR5mRNA expression was increased in colonocytes of NMS mice with CHS. Acute intrarectal instillation of FliC induced transient increase of IPV, reflecting transient CHS *** Altogether, these data suggest a pathophysiological continuum between intestinal dysbiosis a

关键词： Chronic abdominal pain Colonic hypersensitivity Toll-like receptors Intestinal microbiota Early life events

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Comparative effects of α2δ-1 ligands in mouse models of colonic hypersensitivity

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World Journal of Gastroenterology 2016年第31期22卷 7111-7123页

作者： Mathieu Meleine Ludivine Boudieu Agathe Gelot Emilie Muller Amandine Lashermes Julien Matricon Celine Silberberg Vassilia Theodorou Alain Eschalier Denis Ardid frederic a carvalho Clermont Université Université d'Auvergne INSERM 1107 Neuro-Dol Université d’Auvergne INSERM 1107 Neuro-Dol INRA EI-Purpan UMR 1054 Neuro-Gastroenterology and Nutrition

AIM: To investigate anti-hypersensitive effects of α2δ-1 ligands in non-inflammatory and inflammationassociated colonic hypersensitivity(CHS) mouse ***: To induce an inflammation-associated CHS, 1% dextran sulfate sodium(DSS) was administered to C57Bl/6J male mice, in drinking water, for 14 d. Regarding the non-inflammatory neonatal maternal separation(NMS)-induced CHS model, wild-type C57BI/6J pups were isolated from their mother from day 2 to day 14(P2 to P14), three hours per day(from 9:00 a.m. to 12:00 p.m.). Colorectal distension was performed by inflating distension probe from 20 μL to 100 μL by 20 μL increment step every 10 s. After a first colorectal distension(CRD), drugs were administered subcutaneously, in a cumulative manner,(Gabapentin at 30 mg/kg and 100 mg/kg; Pregabalin at 10 mg/kg and 30 mg/kg; Carbamazepine at 10 mg/kg and 30 mg/kg) and a second CRD was performed one hour after each ***: The visceromotor response(VMR) to CRD was increased by our NMS paradigm protocol in comparison to non-handled(NH) mice, considering the highest distension volumes(80 μL: 0.783 ± 0.056 mV /s vs 0.531 ± 0.034 m V/s, P < 0.05 and 100 μL: 1.087 ± 0.056 m V/s vs 0.634 ± 0.038 m V/s, P < 0.05 for NMS and NH mice, respectively). In the inflammationassociated CHS, DSS-treated mice showed a dramatic and significant increase in VMR at 60 and 80 μL distension volumes when compared to control mice(60 μL: 0.920 ± 0.079 m V/s vs 0.426 ± 0.100 m V/s P < 0.05 and 80 μL: 1.193 ± 0.097 mV /s vs 0.681 ± 0.094 mV /s P < 0.05 for DSS- and Water-treated mice, respectively). Carbamazepine failed to significantly reduce CHS in both models. Gabapentin significantly reduced CHS in the DSS-induced model for both subcutaneous injections at 30 or 100 mg/kg. Pregabalin s i g n i f i c a n t l y r e d u c e d V M R t o C R D i n t h e n o n-inflammatory NMS-induced CHS model for the acute subcutaneous administration of the highest cumulative dose(30 mg/kg) and significan

关键词： Neonatal maternal separation Dextran sulfate sodium Colonic hypersensitivity mouse models Colorectal distension α2δ-1 ligands

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