RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Sporisorium reilianum f. sp. reilianum (SSR) is a fungus isolated from a medicinal plant. Recorded in the "Compilation of National Chinese Herbal Medicine" and "Compendium of Materia Medica," it was used for preventing and treating intestinal diseases, enhancing immune function, etc. In this study, we investigated the chemical composition and bioactivity of SSR. Network pharmacology is utilized for predictive analysis and targeting pathway studies of anti-inflammatory bowel disease (IBD) mechanisms. Pharmacological activity against enteritis is evaluated using zebrafish (Danio rerio) as model animals. AIM OF THE STUDY: To reveal the treatment of IBD by SSR used as traditional medicine and food, based on molecular biology identification of SSR firstly, and the pharmaceutical components & its toxicities, biological activity & mechanism of SSR were explored. MATERIALS AND METHODS: Using chromatography and zebrafish IBD model induced by dextran sulfate sodium (DSS), nine compounds were first identified by nuclear magnetic resonance (NMR). The toxicity of ethanol crude extract and monomers from SSR were evaluated by evaluating the phenotypic characteristics of zebrafish embryos and larvae, histomorphology and pathology of the zebrafish model guided by network pharmacology were conducted. RESULTS: The zebrafish embryo development did not show toxicity. The molecular docking and enrichment pathway results predicted that metabolites 3 & 4 (N-trans- feruloyl-3-methoxytyramine & N-cis-feruloyl-3-methoxytyramine) and 7 & 8 (4-N- trans-p-coumaroyltyramine & 4-N-cis--p-coumaroyltyramine) have anti-enteritis activities. This paper lays an experimental foundation for developing new drugs and functional foods.
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Enteritis , Pez Cebra , Animales , Enteritis/tratamiento farmacológico , Enteritis/patología , Enteritis/prevención & control , Modelos Animales de Enfermedad , Sulfato de Dextran , Embrión no Mamífero/efectos de los fármacos , Larva/efectos de los fármacos , Farmacología en Red , Simulación del Acoplamiento Molecular , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificaciónAsunto(s)
Enteritis , Eosinofilia , Gastritis , Peritonitis , Humanos , Eosinofilia/diagnóstico , Eosinofilia/patología , Gastritis/diagnóstico , Gastritis/complicaciones , Enteritis/diagnóstico , Enteritis/complicaciones , Enteritis/patología , Peritonitis/diagnóstico , Peritonitis/etiología , Masculino , Tomografía Computarizada por Rayos X , Femenino , Resultado del TratamientoRESUMEN
Eosinophilic gastrointestinal diseases (EGIDs) are a group of diseases characterized by selective eosinophil infiltration of the gastrointestinal (GI) tract in the absence of other causes of eosinophilia. These diseases are generally driven by type 2 inflammation, often in response to food allergen exposure. Among all EGIDs, the clinical presentation often includes a history of atopic disease with a variety of GI symptoms. EGIDs are traditionally separated into eosinophilic esophagitis (EoE) and non-EoE EGIDs. EoE is relatively better understood and now associated with clinical guidelines and 2 US Food and Drug Administration-approved treatments, whereas non-EoE EGIDs are rarer and less well-understood diseases without US Food and Drug Administration-approved treatments. Non-EoE EGIDs are further subclassified by the area of the GI tract that is involved; they comprise eosinophilic gastritis, eosinophilic enteritis (including eosinophilic duodenitis), and eosinophilic colitis. As with other GI disorders, the disease presentations and mechanisms differ depending on the involved segment of the GI tract; however, the differences between EoE and non-EoE EGIDs extend beyond which GI tract segment is involved. The aim of this article is to summarize the commonalities and differences between the clinical presentations and disease mechanisms for EoE and non-EoE EGIDs.
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Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Humanos , Eosinofilia/inmunología , Eosinofilia/diagnóstico , Eosinofilia/patología , Enteritis/diagnóstico , Enteritis/inmunología , Enteritis/patología , Gastritis/diagnóstico , Gastritis/inmunología , Gastritis/patología , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/inmunología , Esofagitis Eosinofílica/patología , Animales , Eosinófilos/inmunología , Eosinófilos/patología , Enfermedades Gastrointestinales/inmunología , Enfermedades Gastrointestinales/diagnósticoRESUMEN
Intraepithelial lymphocytes (IEL) reside in the epithelium at the interface between the contents of the intestinal lumen and the sterile environment of the lamina propria. Because of this strategic location, IEL play a crucial role in various immunological processes, ranging from pathogen control to tissue stability. In mice and humans, IEL exhibit high diversity, categorized into induced IEL (conventional CD4 and CD8αß T cells) and natural IEL (TCRαßCD8αα, TCRγδ, and TCRneg IEL). In chickens, however, the subpopulations of IEL and their functions in enteric diseases remain unclear. Thus, we conducted this study to investigate the role of IEL populations during necrotic enteritis (NE) in chickens. At 14 days of age, sixty-three Specific-pathogen-free (SPF) birds were randomly assigned to three treatments: Control (sham challenge), Eimeria maxima challenge (EM), and Eimeria maxima + Clostridium Perfringens (C. Perfringens) co-challenge (EM/CP). The EM and EM/CP birds were infected with Eimeria maxima at day 14 of age, and EM/CP birds were additionally orally inoculated with C. perfringens at days 18 and 19 of age. Birds were weighed at days 18, 20, and 26 of age to assess body weight gain (BWG). At 20 days of age (1 day-post C. perfringens infection; dpi), and 26 days of age (7 dpi), 7 birds per treatment were euthanized, and jejunum was harvested for gross lesion scores, IEL isolation, and gene expression. The EM/CP birds exhibited subclinical NE disease, lower BWG and shorter colon length. The Most changes in the IEL populations were observed at 1 dpi. The EM/CP group showed substantial increases in the total number of natural IEL subsets, including TCRαß+CD4-CD8-, TCRαß+CD8αα+, TCRγδ+, TCRneg and innate CD8α (iCD8α) cells by at least two-fold. However, by 7 dpi, only the number of TCRαß+CD4-CD8- and TCRαß+CD8αα+ IEL maintained their increase in the EM/CP group. The EM/CP group had significantly higher expression of proinflammatory cytokines (IL-1ß and IFN-γ) and Osteopontin (OPN) in the jejunum at 1 dpi. These findings suggest that natural IEL with innate and innate-like functions might play a critical role in the host response during subclinical NE, potentially conferring protection against C. perfringens infection.
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Eimeria , Enteritis , Linfocitos Intraepiteliales , Humanos , Animales , Ratones , Pollos , Linfocitos Intraepiteliales/patología , Intestinos/patología , Clostridium perfringens/fisiología , Eimeria/fisiología , Enteritis/veterinaria , Enteritis/patología , Receptores de Antígenos de Linfocitos TRESUMEN
A 69-year-old woman presented to our department with the chief complaint of diarrhea. She had undergone left nephrectomy for renal cancer 14 years earlier. Three years earlier, metastasis was detected in the left retroperitoneal cavity, and pazopanib administration was initiated. In the 29th month after the start of chemotherapy, the patient developed diarrhea, and on the 31st month, computed tomography showed thickening of the intestinal wall. Colonoscopy revealed white villi, intramucosal hemorrhage in the terminal ileum, and rough inflammatory mucosa with inflammatory polyps extending from the transverse to the sigmoid colon. Suspecting pazopanib-induced enteritis, we discontinued the medication, and the diarrhea resolved within 3 days. On the 21st day after discontinuation, colonoscopy revealed that the inflammatory polyps had shrunk, and the inflammatory findings had improved. Biopsy of the white villi of the ileum revealed histiocytes. The patient resumed treatment with pazopanib at 400 mg/day and developed soft stool on the 7th day after resumption. Compared with other tyrosine-kinase inhibitor-induced enteritis cases, this case showed less bleeding and more extensive inflammatory findings. There are similarities as well as differences from cases of previously reported pazopanib-induced enteritis. The mechanisms and characteristics of this disease require further investigation.
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Carcinoma de Células Renales , Enteritis , Indazoles , Neoplasias Renales , Pirimidinas , Sulfonamidas , Humanos , Femenino , Pirimidinas/efectos adversos , Pirimidinas/uso terapéutico , Anciano , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/secundario , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Enteritis/inducido químicamente , Enteritis/patología , Diarrea/inducido químicamente , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/uso terapéutico , ColonoscopíaRESUMEN
Radiation-induced enteritis, a significant concern in abdominal radiation therapy, is associated closely with gut microbiota dysbiosis. The mucus layer plays a pivotal role in preventing the translocation of commensal and pathogenic microbes. Although significant expression of REGγ in intestinal epithelial cells is well established, its role in modulating the mucus layer and gut microbiota remains unknown. The current study revealed notable changes in gut microorganisms and metabolites in irradiated mice lacking REGγ, as compared to wild-type mice. Concomitant with gut microbiota dysbiosis, REGγ deficiency facilitated the infiltration of neutrophils and macrophages, thereby exacerbating intestinal inflammation after irradiation. Furthermore, fluorescence in situ hybridization assays unveiled an augmented proximity of bacteria to intestinal epithelial cells in REGγ knockout mice after irradiation. Mechanistically, deficiency of REGγ led to diminished goblet cell populations and reduced expression of key goblet cell markers, Muc2 and Tff3, observed in both murine models, minigut organoid systems and human intestinal goblet cells, indicating the intrinsic role of REGγ within goblet cells. Interestingly, although administration of broad-spectrum antibiotics did not alter the goblet cell numbers or mucin 2 (MUC2) secretion, it effectively attenuated inflammation levels in the ileum of irradiated REGγ absent mice, bringing them down to the wild-type levels. Collectively, these findings highlight the contribution of REGγ in counteracting radiation-triggered microbial imbalances and cell-autonomous regulation of mucin secretion.
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Enteritis , Microbioma Gastrointestinal , Células Caliciformes , Homeostasis , Ratones Noqueados , Mucina 2 , Complejo de la Endopetidasa Proteasomal , Animales , Humanos , Ratones , Disbiosis/microbiología , Disbiosis/metabolismo , Enteritis/microbiología , Enteritis/metabolismo , Enteritis/patología , Células Caliciformes/patología , Células Caliciformes/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Ratones Endogámicos C57BL , Mucina 2/metabolismo , Proteínas Asociadas a Pancreatitis/metabolismo , Traumatismos por Radiación/metabolismo , Traumatismos por Radiación/microbiología , Traumatismos por Radiación/patología , Traumatismos Experimentales por Radiación/metabolismo , Traumatismos Experimentales por Radiación/patología , Traumatismos Experimentales por Radiación/microbiología , Factor Trefoil-3/metabolismo , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Complejo de la Endopetidasa Proteasomal/efectos de la radiación , Autoantígenos/genética , Autoantígenos/metabolismo , Autoantígenos/efectos de la radiaciónRESUMEN
BACKGROUND: Necrotic enteritis (NE) is a severe intestinal infection that affects both humans and poultry. It is caused by the bacterium Clostridium perfringens (CP), but the precise mechanisms underlying the disease pathogenesis remain elusive. This study aims to develop an NE broiler chicken model, explore the impact of the microbiome on NE pathogenesis, and study the virulence of CP isolates with different toxin gene combinations. METHODS: This study established an animal disease model for NE in broiler chickens. The methodology encompassed inducing abrupt protein changes and immunosuppression in the first experiment, and in the second, challenging chickens with CP isolates containing various toxin genes. NE was evaluated through gross and histopathological scoring of the jejunum. Subsequently, jejunal contents were collected from these birds for microbiome analysis via 16S rRNA amplicon sequencing, followed by sequence analysis to investigate microbial diversity and abundance, employing different bioinformatic approaches. RESULTS: Our findings reveal that CP infection, combined with an abrupt increase in dietary protein concentration and/or infection with the immunosuppressive variant infectious bursal disease virus (vIBDV), predisposed birds to NE development. We observed a significant decrease (p < 0.0001) in the abundance of Lactobacillus and Romboutsia genera in the jejunum, accompanied by a notable increase (p < 0.0001) in Clostridium and Escherichia. Jejunal microbial dysbiosis and severe NE lesions were particularly evident in birds infected with CP isolates containing cpa, netB, tpeL, and cpb2 toxin genes, compared to CP isolates with other toxin gene combinations. Notably, birds that did not develop clinical or subclinical NE following CP infection exhibited a significantly higher (p < 0.0001) level of Romboutsia. These findings shed light on the complex interplay between CP infection, the gut microbiome, and NE pathogenesis in broiler chickens. CONCLUSION: Our study establishes that dysbiosis within the jejunal microbiome serves as a reliable biomarker for detecting subclinical and clinical NE in broiler chicken models. Additionally, we identify the potential of the genera Romboutsia and Lactobacillus as promising candidates for probiotic development, offering effective alternatives to antibiotics in NE prevention and control.
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Infecciones por Clostridium , Enteritis , Microbioma Gastrointestinal , Enfermedades de las Aves de Corral , Humanos , Animales , Clostridium perfringens/genética , Pollos/genética , ARN Ribosómico 16S/genética , Disbiosis , Yeyuno/química , Yeyuno/patología , Enteritis/microbiología , Enteritis/patología , Enteritis/veterinaria , Infecciones por Clostridium/veterinaria , Infecciones por Clostridium/microbiología , Infecciones por Clostridium/patología , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/patologíaRESUMEN
BACKGROUND: Eosinophilic gastroenteritis (EGE) is a rare eosinophilic infiltrative disorder. In Japan, EGE is diagnosed using clinical symptoms as well as microscopic, haematologic and histopathological findings. In this study, we examined the usefulness of laboratory data in the diagnosis of EGE. METHODS: Patients who were diagnosed with EGE at Fujita Health University Bantane Hospital between April 2015 and December 2020 were enrolled in this study and their data was retrospectively analysed. We evaluated their medical history, laboratory data including leukocyte count, eosinophil count, immunoglobulin (Ig) E, thymus and activation-regulated chemokine (TARC), C-reactive protein (CRP), etc. and histopathological data were collected from the electronic medical records. RESULTS: One hundred twelve of 168 patients who were treated for EGE could be analysed. The peripheral eosinophil count was correlated with the duodenal or ascending colon eosinophil count; moreover, the blood lymphocyte count and the TARC were correlated with the transverse colon eosinophil count. Multivariate regression analysis showed correlations only in the oesophagus, stomach and duodenum. Specifically, correlations were noted between blood eosinophils and gastric eosinophils, blood eosinophils and duodenal eosinophils, blood lymphocytes and gastric eosinophils, blood IgE and oesophageal, gastric and duodenal eosinophils and CRP and oesophageal eosinophils. CONCLUSION: The extent of blood eosinophil count, lymphocyte count, IgE and CRP elevation together with clinical features and pathology can be incorporated into a diagnostic scoring criteria system to improve the accuracy of diagnosing this uncommon condition in the future.
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Enteritis , Eosinofilia , Gastritis , Laboratorios Clínicos , Humanos , Estudios Retrospectivos , Enteritis/diagnóstico , Enteritis/patología , Eosinófilos/patología , Recuento de Leucocitos , Inmunoglobulina E , Proteína C-ReactivaRESUMEN
Anti-interleukin (IL)-10 may preserve broiler performance during coccidiosis by diminishing Eimeria spp. host-evasion but has not been evaluated during secondary Clostridium perfringens challenge (necrotic enteritis). Early Salmonella Typhimurium inoculation is implemented in some models to improve repeatability-a potential confounder due to Salmonella using similar IL-10 host evasion pathways. The objective was to evaluate performance and disease outcomes in broilers fed anti-IL-10 during necrotic enteritis challenge ± S. Typhimurium. Three 42 d replicate studies in wire-floor cages (32 cages/replicate) were conducted with Ross 308 chicks assigned to diets ± 0.03% anti-IL-10 for 25 d before moving to floor pens for the study remainder. In replicates 1 and 2, 640 chicks were placed at hatch (20/cage) and inoculated with sterile saline ± 1 × 108 colony forming units (CFU) S. Typhimurium. Replicate 3 placed 480 chicks (15/cage) at hatch. On d 14, S. Typhimurium-inoculated chicks (replicates 1 and 2) or those designated for challenge (replicate 3) were inoculated with 15,000 sporulated Eimeria maxima M6 oocysts. On d 18 and 19, half the E. maxima-challenged chicks were gavaged with 1 × 108 CFU C. perfringens. Body weight (BW) and feed intake were measured throughout, while 6 chicks/ treatment were scored for jejunal lesions at 7 and 3 d postinoculation (pi) with E. maxima and C. perfringens, respectively. Oocyst shedding was measured at 8 and 4 dpi with E. maxima and C. perfringens, respectively. Performance and oocyst shedding were analyzed with diet and challenge fixed effects (SAS 9.4), whereas lesion scores and mortalities were analyzed by ordinal logistic regression (R 4.2.2; P ≤ 0.05). In replicate 3, no wk 3 feed conversion ratio (FCR) differences were observed between chicks fed anti-IL-10 challenged with E. maxima ± C. perfringens, whereas control-fed chicks had a 50 point less efficient FCR during E. maxima + C. perfringens challenge vs. E. maxima only (P = 0.04). Outcomes suggest anti-IL-10 may preserve bird feed efficiency during necrotic enteritis challenge in models without S. Typhimurium.
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Infecciones por Clostridium , Coccidiosis , Eimeria , Enteritis , Enfermedades de las Aves de Corral , Animales , Pollos , Salmonella typhimurium , Infecciones por Clostridium/prevención & control , Infecciones por Clostridium/veterinaria , Interleucina-10 , Coccidiosis/prevención & control , Coccidiosis/veterinaria , Clostridium perfringens , Dieta , Enteritis/prevención & control , Enteritis/veterinaria , Enteritis/patología , Enfermedades de las Aves de Corral/prevención & control , Alimentación Animal/análisisRESUMEN
Conjoining of the major pancreatic duct and common bile duct at the major duodenal papilla (MDP) is suspected to predispose cats to the clinical syndrome of "triaditis." However, microanatomy of the MDP or presence of lesions at the MDP has not been assessed in cats with or without triaditis. The aims of this study were to characterize feline MDP histomorphology and to identify associations between MDP anatomy/disease and the presence of biliary, pancreatic, or intestinal inflammation or neoplasia. Histologic assessment was prospectively performed on the MDP, duodenum, jejunum, ileum, liver, and pancreas from 124 client-owned cats undergoing postmortem examination. The majority of cats (104/124, 84%) had a complex ductular network at the MDP, with no distinction between pancreatic and common bile ducts. Lymphoid aggregates at the MDP were common (63/124, 51%). Inflammation of the MDP (MDPitis) was present in 35 of 124 cats (28%) and was often concurrent with cholangitis, pancreatitis, or enteritis (32/35, 91%), but was only associated with enteritis (19/35, 54%, P < .05). Triaditis was less common (19/124, 15%), but was associated with both conjoined MDP anatomy (19/19, 100%, P < .05) and MDPitis (12/19, 63%, P < .05). Neoplasia was present in 37 of 124 cats (29%), with lymphoma (28/37, 78%) predominating. Enteropathy-associated T-cell lymphoma type 2 (EATL2) was most common (n = 16/37, 43%) and was associated with triaditis and MDPitis (P < .05). These findings suggest that anatomy, immune activation, and/or inflammation of the MDP may play a role in the pathogenesis of triaditis. Further studies are needed to elucidate the relationships between triaditis, MDPitis, and EATL2.
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Ampolla Hepatopancreática , Enfermedades de los Gatos , Enteritis , Neoplasias , Humanos , Gatos , Animales , Ampolla Hepatopancreática/patología , Páncreas , Inflamación/patología , Inflamación/veterinaria , Enteritis/patología , Enteritis/veterinaria , Neoplasias/patología , Neoplasias/veterinaria , Enfermedades de los Gatos/patologíaRESUMEN
Host cellular responses against Clostridium perfringens (CP), the causative agent of necrotic enteritis (NE) in chickens, are poorly understood. In the present study, we first tested the NE-producing ability of seven netB+ CP strains (CP5, CP18, CP26, CP64, CP67, CP68, and NCNE-1), using an experimental infection model of broiler chickens. Evaluation of intestinal gross lesions showed that all the strains, except CP5, were able to produce NE, while CP26 and CP64 strains produced relatively more severe lesions when compared with other groups. Next, cellular responses in the cecal tonsil (CT), bursa of Fabricius, and spleen were evaluated in chickens infected with strains representing variation in the level of virulence, namely, avirulent CP5, virulent CP18, and a relatively more virulent CP26 strain. Immunophenotyping analysis showed that CT or splenic macrophage frequencies were significantly higher in CP18- and CP26-infected chickens compared with uninfected controls, while the frequencies of γδ T-cells and B-cells in the CT of CP26-infected chickens were significantly higher than those in the uninfected, CP5- or CP18-infected groups. The T-cell analysis showed that chickens infected with CP18 and CP26 had a significantly higher number of splenic CD4+ and CD8+ T-cells expressing CD44 and CD28 activation molecules, while CP26-infected chickens also had significantly increased CT frequency of these activated CD4+ and CD8+ T-cells when compared with uninfected or CP5-infected groups. Collectively, our findings suggested that cellular responses, including activation of T-cells, are selectively induced against virulent CP strains and that the NE-producing characteristics of this pathogen may influence the outcome of immunity to NE.
Respuestas inmunes celulares en tejidos linfoides de pollos de engorde infectados experimentalmente con cepas de Clostridium perfringens productoras de enteritis necrótica. Las respuestas celulares del huésped contra Clostridium perfringens (CP), el agente causante de la enteritis necrótica (NE) en pollos, son poco conocidas. En el presente estudio, primero se analizó la capacidad de producción de enteritis necrótica de siete cepas de C. perfringens netB+ (CP5, CP18, CP26, CP64, CP67, CP68 y NCNE-1), utilizando un modelo de infección experimental de pollos de engorde. La evaluación de las lesiones macroscópicas intestinales mostró que todas las cepas, excepto CP5, podían producir enteritis necrótica, mientras que las cepas CP26 y CP64 produjeron lesiones relativamente más severas en comparación con los otros grupos. Posteriormente, se evaluaron las respuestas celulares en las tonsilas cecales (CT), la bolsa de Fabricio y en el bazo de pollos infectados con cepas que representan variaciones en el nivel de virulencia, por ejemplo las cepas CP5 avirulenta, CP18 virulenta y la cepa CP26 relativamente más virulenta. El análisis de inmunofenotipado mostró que las frecuencias de los macrófagos esplénicos o de las tonsilas cecales fueron significativamente más altas en los pollos infectados con las cepas CP18 y CP26 en comparación con los controles no infectados, mientras que las frecuencias de células T γd y células B en tonsilas cecales de los pollos infectados con la cepa CP26 fueron significativamente más altas que las de los pollos de los grupos no infectados, o infectados con las cepas CP5 o CP18. El análisis de células T mostró que los pollos infectados con las cepas CP18 y CP26 tenían un número significativamente mayor de células esplénicas T CD4+ y CD8+ que expresaban moléculas de activación CD44 y CD28, mientras que los pollos infectados con la cepa CP26 también tenían una frecuencia significativamente mayor en las tonsilas cecales de estas células T CD4+ y CD8+ activadas en comparación con grupos no infectados o infectados con la cepa CP5. En conjunto, estos hallazgos sugirieron que las respuestas celulares, incluida la activación de las células T, se inducen selectivamente contra las cepas virulentas de C. perfringens y que las características productoras de enteritis necrótica de este patógeno pueden influir en el resultado de la inmunidad contra la enteritis necrótica.
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Infecciones por Clostridium , Enteritis , Enfermedades de las Aves de Corral , Animales , Clostridium perfringens/fisiología , Infecciones por Clostridium/veterinaria , Infecciones por Clostridium/patología , Pollos , Linfocitos T CD8-positivos/patología , Enteritis/veterinaria , Enteritis/patología , Enfermedades de las Aves de Corral/patología , Tejido Linfoide/patología , Inmunidad Celular , Necrosis/veterinariaRESUMEN
BACKGROUND: Eosinophilic gastritis/gastroenteritis (EoG/EoGE) are rare disorders with pathologic gastric and/or small intestinal eosinophilia lacking an approved therapy. An allergic mechanism is postulated but underexplored mechanistically and therapeutically. OBJECTIVE: We evaluated the effectiveness of a food allergen-free diet (elemental formula) in controlling gastrointestinal eosinophilia in adult EoG/EoGE. METHODS: Adults aged 18 to 65 years with histologically active EoG/EoGE (≥30 eosinophils per high-power field) in the stomach and/or duodenum and gastrointestinal symptoms within the month preceding enrollment were prospectively enrolled onto a single-arm clinical trial to receive elemental formula for 6 consecutive weeks. The primary end point was percentage of participants with complete histologic remission (<30 eosinophils per high-power field in both stomach and duodenum). Exploratory outcomes were improvement in symptoms, endoscopy results, blood eosinophilia, quality of life, Physician Global Assessment score, and EoG-relevant gastric transcriptome and microbiome. RESULTS: Fifteen adults (47% male, average age 37.7 years, average symptom duration 8.8 years) completed the trial. Multi-gastrointestinal segment involvement affected 87%. All subjects had complete histologic remission in the stomach (P = .002) and duodenum (P = .001). Scores improved in overall PhGA (P = .002); EGREFS (P = .003); EGDP (P = .002); SODA pain intensity (P = .044), non-pain (P = .039), and satisfaction (P = .0024); and PROMIS depression (P = .0078) and fatigue (P = .04). Food reintroduction reversed these improvements. The intervention was well tolerated in 14 subjects, with 1 serious adverse event reported in 1 subject. CONCLUSION: An amino acid-based elemental diet improves histologic, endoscopic, symptomatic, quality-of-life, and molecular parameters of EoG/EoGE; these findings and disease recurrence with food trigger reintroduction support a dominant role for food allergens in disease pathogenesis. CLINICALTRIALS: gov Identifier: NCT03320369.
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Enteritis , Eosinofilia , Esofagitis Eosinofílica , Hipersensibilidad a los Alimentos , Gastroenteritis , Adulto , Masculino , Humanos , Femenino , Estudios Prospectivos , Aminoácidos , Calidad de Vida , Enteritis/patología , Eosinofilia/tratamiento farmacológico , Alérgenos/uso terapéutico , Alimentos FormuladosRESUMEN
BACKGROUND: The mycotoxin deoxynivalenol (DON) is a frequent contaminant of grain and cereal products worldwide. Exposure to DON can cause gastrointestinal inflammation, disturb gut barrier function, and induce gut dysbiosis in vivo under basal conditions, but little is known about the effects of DON ingestion in individuals with pre-existing gastrointestinal disease. OBJECTIVES: Mice were orally exposed to 10 and 100 µg/kg bw/day of DON, corresponding to 10 to 100-fold human tolerable daily intake concentrations, and to the translation in mice of current human daily intake. The effects of DON exposure were explored under steady-state conditions, and in murine models of enteritis and colorectal cancer (CRC). RESULTS: After 8 days of DON exposure, an increase of histomorphological and molecular parameters of epithelial proliferation were observed in normal mice, from the duodenum to the colon. The same exposure in a murine model of indomethacin-induced enteritis led to exacerbation of lesion development and induction of ileal cytokines. DON exposure also worsened the development of colitis-associated CRC in mice as shown by increases in endoscopic and histological colitis scores, tumor grades, and histological hyperplasia. In colon of DON-exposed mice, upstream and downstream ERK signaling genes were upregulated including Mapk1, Mapk3, Map 2k1, Map2k2 core ERK pathway effectors, and Bcl2 and Bcl2l1 antiapoptotic genes. The effects observed in the CRC model were associated with alterations in cecal microbiota taxonomic composition and metabolism of bacterial fucose and rhamnose. Strong Spearman's correlations were revealed between the relative abundance of the changed bacterial genera and CRC-related variables. DISCUSSION: Ingestion of DON mycotoxin at concentrations representative of human real-world exposure worsened the development of indomethacin-induced enteritis and colitis-associated CRC in mice. Our results suggest that even at low doses, which are currently tolerated in the human diet, DON could promote the development of intestinal inflammatory diseases and CRC.
Asunto(s)
Colitis , Neoplasias Colorrectales , Enteritis , Micotoxinas , Ratones , Humanos , Animales , Enteritis/inducido químicamente , Enteritis/patología , Dieta , Indometacina/toxicidad , Neoplasias Colorrectales/inducido químicamenteRESUMEN
Necrotic enteritis (NE) and coccidiosis are among the most prevalent infectious diseases in broiler chickens, contributing to large profitability losses. Bacillus subtilis is a promising direct-fed probiotic to counter various pathogens infection in broiler chickens. Here, we performed a meta-analysis to investigate the effects of B. subtilis on broiler chickens performance. A total of 28 studies were selected according to a PRISMA checklist. Random-effect model and mixed-effect model of meta-analysis were fitted to estimate the overall effects of B. subtilis (BS) treatment compared to either the control group (CON) or NE-infected group (NEinf) as a baseline. Hedges' g effect size and its variance were used as estimators of standardized mean difference (SMD) calculation where the results were presented at a 95% confidence interval (95% CI) of the SMD. Overall, NEinf broiler chickens depressed (P < 0.01) body weight (BW), average daily gain (ADG), and feed intake, and elevated (P < 0.01) feed conversion ratio (FCR). Treatment with BS improved ADG and final BW of NEinf with no difference (P = 0.15) between BS and antibiotics (AB), indicating that they had comparable efficacy to treat NE in broiler chickens. BS supplemented to uninfected CON (BSS) improved (P < 0.01) final BW, ADG, and FCR. Compared to CON, BS, and AB failed to recover the FCR but these treatments decreased (P < 0.01) FCR when compared to the NEinf group with similar efficacy (P = 0.97). As expected, NEinf birds had a higher mortality rate (P < 0.01) and higher lesion score (P < 0.01) compared to CON, and treatment using AB and BS successfully decreased (P < 0.01) the mortality rate and lesion score. Compared to BS, AB was more effective to lower (P = 0.01) mortality rate, but comparable (P = 0.65) to minimize lesion score. To conclude, B. subtilis could be an effective natural additive to replace in-feed antibiotics in broiler chickens challenged with C. perfringens. However, the efficacy to reduce mortality rate was better with antibiotics treatment.
Asunto(s)
Infecciones por Clostridium , Enteritis , Enfermedades de las Aves de Corral , Animales , Antibacterianos/uso terapéutico , Bacillus subtilis , Pollos , Dieta/veterinaria , Enfermedades de las Aves de Corral/tratamiento farmacológico , Enfermedades de las Aves de Corral/prevención & control , Enfermedades de las Aves de Corral/patología , Alimentación Animal/análisis , Clostridium perfringens , Peso Corporal , Enteritis/tratamiento farmacológico , Enteritis/veterinaria , Enteritis/patología , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/veterinaria , Infecciones por Clostridium/patologíaRESUMEN
BACKGROUND: Lymphoplasmacytic enteritis (LPE) and low-grade intestinal T cell lymphoma (LGITL) are common diseases in older cats, but their diagnosis and differentiation remain challenging. OBJECTIVES: To summarize the current literature on etiopathogenesis and diagnosis of LPE and LGITL in cats and provide guidance on the differentiation between LPE and LGITL in cats. To provide statements established using evidence-based approaches or where such evidence is lacking, statements based on consensus of experts in the field. ANIMALS: None. METHODS: A panel of 6 experts in the field (2 internists, 1 radiologist, 1 anatomic pathologist, 1 clonality expert, 1 oncologist) with the support of a human medical immunologist, was formed to assess and summarize evidence in the peer-reviewed literature and complement it with consensus recommendations. RESULTS: Despite increasing interest on the topic for clinicians and pathologists, few prospective studies were available, and interpretation of the pertinent literature often was challenging because of the heterogeneity of the cases. Most recommendations by the panel were supported by a moderate or low level of evidence. Several understudied areas were identified, including cellular markers using immunohistochemistry, genomics, and transcriptomic studies. CONCLUSIONS AND CLINICAL IMPORTANCE: To date, no single diagnostic criterion or known biomarker reliably differentiates inflammatory lesions from neoplastic lymphoproliferations in the intestinal tract of cats and a diagnosis currently is established by integrating all available clinical and diagnostic data. Histopathology remains the mainstay to better differentiate LPE from LGITL in cats with chronic enteropathy.
Asunto(s)
Enfermedades de los Gatos , Enteritis , Enfermedades Inflamatorias del Intestino , Humanos , Gatos , Animales , Estudios Prospectivos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/veterinaria , Enteritis/diagnóstico , Enteritis/veterinaria , Enteritis/patología , Linfocitos , Enfermedades de los Gatos/diagnósticoRESUMEN
Having long been considered the mainstay in eosinophilic esophagitis (EoE) diagnosis and pathogenesis, the role of eosinophils has been questioned and might be less important than previously thought. It is well known now that EoE is a Th2-mediated disease with many more disease features than eosinophilic infiltration. With more knowledge on EoE, less pronounced phenotypes or nuances of the disease have become apparent. In fact, EoE might be only the tip of the iceberg (and the most extreme phenotype) with several variant forms, at least three, lying on a disease spectrum. Although a common (food induced) pathogenesis has yet to be confirmed, gastroenterologists and allergologists should be aware of these new phenomena in order to further characterize these patients. In the following review, we discuss the pathogenesis of EoE, particularly those mechanisms beyond eosinophilic infiltration of the esophageal mucosa, non-eosinophilic inflammatory cell populations, the new disease entity EoE-like disease, variant forms of EoE, and the recently coined term mast cell esophagitis.
Asunto(s)
Enteritis , Esofagitis Eosinofílica , Gastritis , Humanos , Esofagitis Eosinofílica/diagnóstico , Eosinófilos/patología , Enteritis/complicaciones , Enteritis/patología , Gastritis/complicacionesRESUMEN
Since the ban or reduction on the use of antibiotic growth promoters (AGPs) in commercial broiler chickens in many countries, avian necrotic enteritis (NE) caused by Clostridium perfringens has re-emerged as one of the biggest threats for the poultry industry worldwide. While the toolbox for controlling NE in the absence of antibiotics consists of a limited number of alternatives for which the overall effectiveness has yet proven to be suboptimal, an effective vaccine would represent the best control strategy for this often-deadly disease. Using a comparative and subtractive reverse vaccinology approach, we previously identified 14 putative antigenic proteins unique to NE-causing strains of C. perfringens. In the current work, the in silico findings were confirmed by PCR and sequencing, and five vaccine candidate proteins were produced and purified subsequently. Among them, two candidates were hypothetical proteins, two candidates were prepilin proteins which are predicted to form the subunits of a pilus structure, and one candidate was a non-heme iron protein. Western blotting and ELISA results showed that immunization of broiler chickens with five of these proteins raised antibodies which can specifically recognize both the recombinant and native forms of the protein in pathogenic C. perfringens.
Asunto(s)
Infecciones por Clostridium , Enteritis , Enfermedades de las Aves de Corral , Animales , Clostridium perfringens/genética , Pollos , Infecciones por Clostridium/prevención & control , Infecciones por Clostridium/veterinaria , Enteritis/patología , Vacunación , Proteínas Fimbrias , NecrosisRESUMEN
BACKGROUND: Daikenchuto (DKT) has positive therapeutic effects on improving various gastrointestinal disorders. The present study investigated whether or not DKT has a potential therapeutic effect on chemotherapy-induced acute small intestinal mucositis (CIM) in a rat model. METHODS: Intraperitoneal injection of 10 mg/kg methotrexate (MTX) every 3 days for a total of 3 doses was used for induction of CIM in a rat model. The MTX and DKT-MTX groups were injected with MTX as above from the first day, and the DKT-MTX and DKT groups were administered 2.7% DKT via the diet at the same time. The rats were euthanized on day 15. RESULTS: The DKT-MTX group showed an improvement in the body weight and conditions of gastrointestinal disorders as well as increased levels of diamine oxidase in plasma and in the small intestinal villi. The pathology results showed that small intestinal mucosal injury in the DKT-MTX group was less severe than that in the MTX group. Immunohistochemistry for myeloperoxidase and malondialdehyde and quantitative real-time polymerase chain reaction (RT-qPCR) for TGF-ß1 and HIF-1α showed that DKT attenuated peroxidative damage. The crypts in the DKT-MTX group contained more Ki-67-positive cells than MTX group. The zonula occluden-1 and claudin-3 results showed that DKT promoted repair of the mucosal barrier. RT-qPCR for the amino acid transporters EAAT3 and BO+AT also confirmed that DKT promoted mucosal repair and thus promoted nutrient absorption. CONCLUSION: DKT protected against MTX-induced CIM in a rat model by reducing inflammation, stimulating cell proliferation, and stabilizing the mucosal barrier.
Asunto(s)
Enteritis , Mucositis , Panax , Ratas , Animales , Metotrexato/toxicidad , Mucositis/inducido químicamente , Mucositis/tratamiento farmacológico , Mucositis/patología , Mucosa Intestinal/metabolismo , Enteritis/patologíaRESUMEN
Clostridium (C.) perfringens is the causative agent of necrotic enteritis (NE), an important enteric disease in poultry. Although a variety of virulence factors have been identified and as such the pathogenesis is well studied, data on colonization and sporulation during passage in the intestinal tract are scarce. This study, therefore, evaluated the behaviour of C. perfringens in the different intestinal compartments of broiler chickens during a NE trial. Necrotic enteritis-associated lesions were mostly found in the jejunum, where they were significantly more severe compared to the duodenum and ileum. Furthermore, a positive correlation between the total number of vegetative C. perfringens cells in the duodenum, jejunum, ileum, or distal colon and disease severity was observed. Additionally, in the caecum and distal colon, C. perfringens was mainly present as a spore. This observation has important consequences for NE treatment and prevention, as both the vegetative cells and C. perfringens spores should be targeted to avoid uptake of spores from the litter and reinfection of the birds after antibiotic treatment.
Asunto(s)
Infecciones por Clostridium , Enteritis , Enfermedades de las Aves de Corral , Animales , Clostridium perfringens , Enteritis/veterinaria , Enteritis/patología , Pollos , Infecciones por Clostridium/veterinaria , Infecciones por Clostridium/patología , Necrosis/veterinaria , Intestinos/patología , Enfermedades de las Aves de Corral/prevención & controlRESUMEN
Eosinophilic gastrointestinal (GI) disorders are a group of conditions marked by pathologic eosinophilic infiltration of one or multiple locations in the GI tract. Conditions include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic enteritis, and eosinophilic colitis. The site and depth of eosinophilic infiltration of the GI tract usually determines clinical presentation. These conditions should be considered in the differential diagnosis for several GI symptoms, such as food impaction or dysphagia. Histopathology is the gold standard for diagnosis of eosinophilic disorders. Nevertheless, findings from endoscopy, barium studies, computed tomography or magnetic resonance imaging, can aid in the diagnosis, by allowing for earlier diagnosis as well as proper management. Eosinophilic gastrointestinal disorders are typically managed with corticosteroids or dietary elimination. A high index of suspicion is required for diagnosis as it can often be challenging.