RESUMEN
BACKGROUND: Mast cells (MCs) are abundant in the inflammatory infiltrate in eosinophilic oesophagitis (EoE), but decrease with disease remission. However, their phenotype, role in the pathophysiology of the disease, and modulation after effective dietary therapy are still unclear. OBJECTIVE: To define the phenotype of oesophageal MCs, their modulation through dietary therapy, and their association with clinical manifestations of EoE. METHODS: Oesophageal mucosal samples from 10 adult patients with EoE obtained before and after effective six-food elimination diet (SFED) therapy, as well as from 10 control subjects were analysed. Eosinophil and MC density were quantified. Gene expression of chemoattractants for eosinophils (CCL11, CCL24, and CCL26), MCs (SCF), and their receptors (CCR3 and SCFR, respectively) were assessed by means of qPCR. Gene and protein expression of specific MC proteases (CPA3, CMA, and TPSB2) were evaluated with qPCR and immunofluorescence. Clinical manifestations and atopic background were recorded. RESULTS: MC density was significantly increased in EoE compared with controls, decreasing after dietary treatment (18.6 to 1.44 cells/hpf, respectively; P < 0.001). The MCTC subtype predominated in the oesophageal mucosa (90%) in both patients with EoE and controls. Gene expression of MC-related proteases, eotaxins, and SCF were up-regulated in patients with EoE, but significantly decreased after therapy, regardless of atopic background. Epithelial peaks of MCs and eosinophils were significantly associated (ρ = 0.80) in EoE and correlated with the symptom score (ρ = 0.78). Gene expression of MC proteases and eotaxins also correlated with the symptom score (P < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: MC and its proteases seem to play a relevant role in the pathophysiology and symptoms of EoE, which can be reversed after effective dietary treatment.
Asunto(s)
Esofagitis Eosinofílica/dietoterapia , Esofagitis Eosinofílica/diagnóstico , Recuento de Leucocitos , Mastocitos/inmunología , Mastocitos/metabolismo , Fenotipo , Adolescente , Adulto , Biomarcadores , Biopsia , Quimiotaxis de Leucocito , Esofagitis Eosinofílica/etiología , Eosinófilos , Esofagoscopía , Femenino , Estudios de Seguimiento , Expresión Génica , Humanos , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Membrana Mucosa/metabolismo , Membrana Mucosa/patología , Adulto JovenRESUMEN
OBJECTIVE: There is substantial inter-individual diversity in the susceptibility of alcoholics to liver injury. Alterations of intestinal microbiota (IM) have been reported in alcoholic liver disease (ALD), but the extent to which they are merely a consequence or a cause is unknown. We aimed to demonstrate that a specific dysbiosis contributes to the development of alcoholic hepatitis (AH). DESIGN: We humanised germ-free and conventional mice using human IM transplant from alcoholic patients with or without AH. The consequences on alcohol-fed recipient mice were studied. RESULTS: A specific dysbiosis was associated with ALD severity in patients. Mice harbouring the IM from a patient with severe AH (sAH) developed more severe liver inflammation with an increased number of liver T lymphocyte subsets and Natural Killer T (NKT) lymphocytes, higher liver necrosis, greater intestinal permeability and higher translocation of bacteria than mice harbouring the IM from an alcoholic patient without AH (noAH). Similarly, CD45+ lymphocyte subsets were increased in visceral adipose tissue, and CD4(+)T and NKT lymphocytes in mesenteric lymph nodes. The IM associated with sAH and noAH could be distinguished by differences in bacterial abundance and composition. Key deleterious species were associated with sAH while the Faecalibacterium genus was associated with noAH. Ursodeoxycholic acid was more abundant in faeces from noAH mice. Additionally, in conventional mice humanised with the IM from an sAH patient, a second subsequent transfer of IM from an noAH patient improved alcohol-induced liver lesions. CONCLUSIONS: Individual susceptibility to ALD is substantially driven by IM. It may, therefore, be possible to prevent and manage ALD by IM manipulation.
Asunto(s)
Disbiosis/complicaciones , Microbioma Gastrointestinal , Hepatopatías Alcohólicas/microbiología , Animales , Susceptibilidad a Enfermedades/microbiología , Femenino , Humanos , Ratones , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Intestinal epithelial dysfunction is a common pathophysiologic feature in irritable bowel syndrome (IBS) patients and might be the link to its clinical manifestations. We previously showed that chronic psychosocial stress induces jejunal epithelial barrier dysfunction; however, whether this epithelial response is gender-specific and might thus explain the enhanced female susceptibility to IBS remains unknown. METHODS: Intestinal responses to acute stress were compared in age-matched groups of healthy women and men (n = 10 each) experiencing low background stress. A 20-cm jejunal segment, was perfused with an isosmotic solution, and intestinal effluents were collected under basal conditions, for 15 min during cold pain stress and for a 45-min recovery period. Epithelial function (net water flux and albumin output), changes in stress hormones, and cardiovascular and psychologic responses to cold stress were measured. KEY RESULTS: Heart rate and blood pressure significantly increased during cold pain stress with no differences between men and women. Adrenocorticotropic hormone and cortisol levels during cold pain stress were significantly higher in men. Basal net water flux and epithelial permeability were similar in men and women. Cold pain stress increased water flux in both groups (72 ± 23 and 107 ± 18 µL min(-1) cm(-1) , respectively; F(5, 90) = 5.5; P = 0.003 for Time) and, interestingly, this was associated with a marked increase of albumin permeability in women but not in men (0.8 ± 0.2 vs.-0.7 ± 0.2 mg/15 min; P < 0.0001). CONCLUSIONS & INFERENCES: Intestinal macromolecular permeability in response to acute experimental stress is increased in healthy women, a mechanism that may contribute to female oversusceptibility to IBS.
Asunto(s)
Mucosa Intestinal/metabolismo , Caracteres Sexuales , Estrés Psicológico/metabolismo , Femenino , Humanos , Síndrome del Colon Irritable/metabolismo , Síndrome del Colon Irritable/fisiopatología , Masculino , Permeabilidad , Estrés Psicológico/fisiopatología , Adulto JovenAsunto(s)
Coma/etiología , Hernia Inguinal/cirugía , Hipotiroidismo/etiología , Mixedema/etiología , Complicaciones Posoperatorias/etiología , Anciano de 80 o más Años , Bradicardia/etiología , Coma/diagnóstico , Comorbilidad , Urgencias Médicas , Epilepsia Generalizada/etiología , Femenino , Humanos , Hidrocortisona/uso terapéutico , Hipopituitarismo/complicaciones , Hipotensión/etiología , Hipotermia/etiología , Hipotiroidismo/diagnóstico , Hipotiroidismo/tratamiento farmacológico , Mixedema/diagnóstico , Complicaciones Posoperatorias/diagnóstico , Estaciones del Año , Tiroxina/uso terapéuticoRESUMEN
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