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Mammalian milk exosomal miRNAs play an important role in maintaining intestinal immune homeostasis and protecting epithelial barrier function, but the specific miRNAs and whether miRNA-mediated mechanisms are responsible for these benefits remain a matter of investigation. This study isolated sheep milk-derived exosomes (sheep MDEs), identifying the enriched miRNAs in sheep MDEs, oar-miR-148a, and oar-let-7b as key components targeting TLR4 and TRAF1, which was validated by a dual-luciferase reporter assay. In dextran sulfate sodium-induced colitis mice, administration of sheep MDEs alleviated colitis symptoms, reduced colonic inflammation, and systemic oxidative stress, as well as significantly increased colonic oar-miR-148a and oar-let-7b while reducing toll-like receptor 4 (TLR4) and TNF-receptor-associated factor 1 (TRAF1) level. Further characterization in TNF-α-challenged Caco-2 cells showed that overexpression of these miRNAs suppressed the TLR4/TRAF1-IκBα-p65 pathway and reduced IL-6 and IL-12 production. These findings indicate that sheep MDEs exert gastrointestinal anti-inflammatory effects through the miRNA-mediated modulation of TLR4 and TRAF1, highlighting their potential in managing colitis.
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INTRODUCTION: Anaphylaxis is a globally increasing allergic reaction that is often fatal. Recently, our previous study reported the possibility of using the modified natural products "sodium R-lipoate (NaRLA) and enzymatically modified isoquercitrin (EMIQ)" as potential novel safe agents against the non-immunological-degranulation of mast cells. METHODS: Here, we extended our previous findings by determining the antianaphylactic activity of 50 and 100 mg/kg body weight of NaRLA and EMIQ (given orally and prior to local or systemic challenge) in mice models of ovalbumin (OVA)-induced IgE-dependent active cutaneous anaphylaxis (ACA) and active systemic anaphylaxis (ASA) in comparison with sulfasalazine (SSZ, amast cell stabilizer). RESULTS: The pre-treatment of mice with NaRLA or EMIQ completely succeeded, as SSZ, in suppression of the increased vascular permeability associated with IgE-dependent ACA and protected the OVA-sensitized mice from fatal ASA by reducing (p < .001) the skin mast cell degranulation, the elevated peritoneal histamine and interleukin-4 levels, along with decreasing the associated sever gastrointestinal and lung histopathological alterations and inflammation. The high dose of EMIQ prevented death in 70% of mice with anaphylactic shock, better than SSZ. DISCUSSION: Our data indicated that NaRLA and EMIQ may be potential prophylactic and therapeutic candidates for the alleviation of atopic and systemic anaphylaxis.
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The expression of clock genes has been observed to be impaired in biopsies from patients with inflammatory bowel disease (IBD). Disruption of circadian rhythms, which occurs in shift workers, has been linked to an increased risk of gastrointestinal diseases, including IBD. The peripheral circadian clock in intestinal epithelial cells (IECs) was previously shown to balance gastrointestinal homeostasis by regulating the microbiome. Here, we demonstrated that the intestinal clock is disrupted in an IBD-relevant mouse model (IL-10-/-). A lack of the intestinal clock gene (Bmal1) in intestinal epithelial cells (IECs) in a chemically and a novel genetically induced colitis model (DSS, Bmal1IEC-/-xIL-10-/-) promoted colitis and dramatically reduced survival rates. Germ-free Bmal1IEC-/- mice colonized with disease-associated microbiota from IL-10-/- mice exhibited increased inflammatory responses, highlighting the importance of the local intestinal clock for microbiota-induced IBD development. Targeting the intestinal clock directly by timed restricted feeding (RF) in IL-10-/- mice restored intestinal clock functions, including immune cell recruitment and microbial rhythmicity; improved inflammatory responses; dramatically enhanced survival rates and rescued the histopathological phenotype. In contrast, RF failed to improve IBD symptoms in Bmal1IEC-/-xIL-10-/- mice, demonstrating the significance of the intestinal clock in determining the beneficial effect of RF. Overall, we provide evidence that intestinal clock dysfunction triggers host immune imbalance and promotes the development and progression of IBD-like colitis. Enhancing intestinal clock function by RF modulates the pathogenesis of IBD and thus could become a novel strategy to ameliorate symptoms in IBD patients.
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Factores de Transcripción ARNTL , Relojes Circadianos , Colitis , Interleucina-10 , Ratones Noqueados , Animales , Relojes Circadianos/genética , Colitis/patología , Colitis/inmunología , Interleucina-10/metabolismo , Interleucina-10/genética , Ratones , Factores de Transcripción ARNTL/metabolismo , Factores de Transcripción ARNTL/genética , Factores de Transcripción ARNTL/deficiencia , Ratones Endogámicos C57BL , Inflamación/patología , Enfermedades Inflamatorias del Intestino/patología , Enfermedades Inflamatorias del Intestino/inmunología , Modelos Animales de Enfermedad , Mucosa Intestinal/patología , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Mucosa Intestinal/metabolismo , Microbioma Gastrointestinal , Ritmo Circadiano , Intestinos/patología , Intestinos/microbiología , Intestinos/inmunologíaRESUMEN
Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a systemic inflammatory disease characterised by elevated serum IgG4, IgG4+ cell infiltration, storiform fibrosis, and obliterative phlebitis. While IgG4-RD can affect various organs, gastrointestinal tract involvement is less common. Here, we report a 70-year-old female with IgG4-RD complicated with diffuse and chronic gastrointestinal inflammation, which led to small intestinal perforation. She had been suffering from anorexia, abdominal pain, vomiting, and diarrhoea and hospitalised due to recurrent ileus. Consequently, she was referred due to small intestinal perforation required for surgical intervention. Pathology revealed acute and chronic inflammation with massive IgG4+ plasmacyte infiltration into mucosa of the small intestine and ischaemic change secondarily caused by chronic inflammation. Random biopsies from the mucosa of stomach, duodenum, ileum, and colon also revealed diffuse and massive IgG4+ plasmacyte infiltration in stomach, duodenum, small intestine, and colon. She was diagnosed with IgG4-RD based on the pathological findings and elevated serum IgG4 levels. Glucocorticoid rapidly ameliorated the symptoms. IgG4-RD may cause gastrointestinal manifestations, and histopathological assessment should be considered, even in the absence of specific characteristics of IgG4-RD.
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Enfermedad Relacionada con Inmunoglobulina G4 , Perforación Intestinal , Intestino Delgado , Humanos , Femenino , Anciano , Enfermedad Relacionada con Inmunoglobulina G4/complicaciones , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Perforación Intestinal/etiología , Perforación Intestinal/diagnóstico , Perforación Intestinal/cirugía , Intestino Delgado/patología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Enfermedad Crónica , Resultado del Tratamiento , Inflamación/diagnóstico , Inflamación/etiología , Glucocorticoides/uso terapéutico , Glucocorticoides/administración & dosificaciónRESUMEN
Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammatory diseases with unknown etiology. Gap junctions composed of connexins (Cxs) have been recently validated as an important factor in the development of IBD. Under IBD-induced inflammatory response in the gut, gap junctions connect multiple signaling pathways involved in the interaction between inflammatory cells with other intestinal cells, which altogether mediate the development of IBD. This paper is a narrative review aiming to comprehensively elucidate the biological function of connexins, especially the ubiquitously and predominantly expressed Cx43, in the pathogenesis of IBD.
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Conexinas , Enfermedades Inflamatorias del Intestino , Humanos , Conexinas/metabolismo , Uniones Comunicantes/metabolismo , Transducción de Señal , Enfermedades Inflamatorias del Intestino/metabolismoRESUMEN
Objective:To explore the effects and mechanism of Salvianolic acid B(SalB)on Parkinson's disease(PD).Methods:Forty-eight C57BL/6 male mice were randomly separated into control group(control)withoutdrugs,model group(MPTP)with intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrah-ydropyridine(MPTP),SalB control group with intraperitoneal injection of SalB,and SalB treatment group(MPTP+SalB).Construction of PD mouse model by intraperitoneal injection of MPTP,and treatment with intraperitoneal injection of SalB.Pole climbing test was applied to assess behavior differences.The time of first black stool excretion and water content of feces were measured to evaluate intestinal dysfunctions.The number of tyrosine hydroxylase(TH)positive cells in substantia nigra and the level of Toll like receptor 4(TLR4)in colon were analyzed by immunohistochemistry.The pathological changes of colonic mucosa were observed by HE staining.The levels of calprotectin(CP)and tumor necrosis factor-α(TNF-α)in colon were determined by ELISA.Western blot was used to determine the level of TH in midbrain,the protein level of TH,tight junction protein(ZO-1),and protein level of TLR4/MyD88/NF-κB signaling pathways which express in colon.Results:Com-pared with the Control group,the climbing time,T-turn time and the first black stool excretion time in MPTP group increased while the fecal water content and the number of TH positive cells in substantia nigra were decreased.Accompanied by TLR4 positive cells in colon,pathological injury score of colonic mucosa,levels of CP and TNF-α in colon increased,expression of TH in midbrain and expression of ZO-1 in colon decreased.Expressions of TLR4,MyD88,Nuclear NF-κB p65 and p-NF-κB p65 in colon increased.Com-pared with MPTP group,SalB treatment shortened the climbing time,T-turn time and the first black stool excretion time in SalB treat-ment group,increased the fecal water content and the number of TH positive cells in substantia nigra,lowered TLR4 positive cells in colon,enhanced expression of TH in midbrain and colon,reduced the pathological injury score of colonic mucosa,significantly decreased levels of CP and TNF-α in colon,enhanced expression of ZO-1 in colon,inhibited expressions of TLR4,MyD88,Nuclear NF-κB p65 and p-NF-κB p65 in colon.Conclusion:SalB can protect the nerves and intestines and alleviate the intestinal inflamma-tion of PD mice,which may be related to the inhibition of TLR4/MyD88/NF-κB signal pathway.
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The intestinal tight junction (TJ) barrier is a crucial defense mechanism that prevents the passage of intestinal content into the intestinal wall, tissue, and systemic circulation. A compromised intestinal TJ barrier has been identified as a significant factor in inflammatory bowel disease (IBD), necrotizing enterocolitis, and other gut-related inflammatory conditions. Recent studies have revealed the importance of the probiotic bacterial strains of Bifidobacterium in protecting against intestinal inflammation and IBD pathogenesis via the regulation of intestinal TJ barrier function. Numerous species and strains of Bifidobacterium have been found to regulate TJ proteins and the signaling pathways responsible for maintaining intestinal barrier integrity and permeability. In this review, we provide a summary of recent studies that highlight the regulatory role of Bifidobacterium species and the strain effect on the intestinal TJ barrier. We also discuss the intracellular mechanisms involved in Bifidobacterium modulation of the intestinal barrier and the potential therapeutic efficacy of targeting the barrier function to regulate intestinal inflammation.
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Dairy products are a good source of essential nutrients and past reviews have shown associations of dairy consumption with decreased systemic inflammation. Links between dairy intake and gastrointestinal (GI) inflammation are under-investigated. Therefore, we examined associations between reported dairy intake and markers of GI inflammation in healthy adults in a cross-sectional observational study, hypothesizing a negative association with yogurt intake, suggesting a protective effect, and no associations with total dairy, fluid milk, and cheese intake. Participants completed 24-h dietary recalls and a food frequency questionnaire (FFQ) to assess recent and habitual intake, respectively. Those who also provided a stool sample (n = 295), and plasma sample (n = 348) were included in analysis. Inflammation markers from stool, including calprotectin, neopterin, and myeloperoxidase, were measured along with LPS-binding protein (LBP) from plasma. Regression models tested associations between dairy intake variables and inflammation markers with covariates: age, sex, and body mass index (BMI). As yogurt is episodically consumed, we examined differences in inflammation levels between consumers (>0 cup equivalents/day reported in recalls) and non-consumers. We found no significant associations between dairy intake and markers of GI inflammation. In this cohort of healthy adults, dairy intake was not associated with GI inflammation.
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Inflamación , Complejo de Antígeno L1 de Leucocito , Humanos , Adulto , Estudios Transversales , Índice de Masa Corporal , HecesRESUMEN
BACKGROUND AND PURPOSE: Intestinal inflammation and gut microbiota dysbiosis contribute to Parkinson disease (PD) pathogenesis, and growing evidence suggests associations between inflammatory bowel diseases (IBD) and PD. Considered as markers of chronic gastrointestinal inflammation, elevated serum anti-Saccharomyces cerevisiae antibody (ASCA) levels, against certain gut fungal components, are related to IBD, but their effect on PD is yet to be investigated. METHODS: Serum ASCA IgG and IgA levels were measured using an enzyme-linked immunosorbent assay, and the gut mycobiota communities were investigated using ITS2 sequencing and analyzed using the Qiime pipeline. RESULTS: The study included 393 subjects (148 healthy controls [HCs], 140 with PD, and 105 with essential tremor [ET]). Both serum ASCA IgG and IgA levels were significantly higher in the PD group than in the ET and HC groups. Combining serum ASCA levels and the occurrence of constipation could discriminate patients with PD from controls (area under the curve [AUC] = 0.81, 95% confidence interval [CI] = 0.76-0.86) and from patients with ET (AUC = 0.85, 95% CI = 0.79-0.89). Furthermore, the composition of the gut fungal community differed between the PD and HC groups. The relative abundances of Saccharomyces cerevisiae, Aspergillus, Candida solani, Aspergillus flavus, ASV601_Fungi, ASV866_Fungi, and ASV755_Fungi were significantly higher in the PD group, and enriched Malassezia restricta was found in the HC group. CONCLUSIONS: Our study identified elevated serum ASCA levels and enriched gut Saccharomyces cerevisiae in de novo PD.
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Dopamine (DA) is a catecholamine regulatory molecule with potential role in physiology and physiopathology of the intestinal tract. Various cellular sources of DA have been indicated as enteric neurons, immune cells, intestinal flora and gastrointestinal epithelium. Moreover, DA is produced by nutritional tyrosine. All the five DA receptors, actually described, are present throughout the gut. Current knowledge of DA in this area is reviewed, focusing on gastrointestinal function in health and during inflammation. Research on animal models and humans are reported. A major obstacle to understanding the physiologic and/or pharmacological roles of enteric DA is represented by the multiplicity of receptors involved in the responses together with many signalling pathways related to each receptor subtype. It is mandatory to map precisely the distributions of DA receptors, to determine the relevance of a receptor in a specific location in order to explore novel therapies directed to dopaminergic targets that may be useful in the control of intestinal inflammation.
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Dopamina , Receptores Dopaminérgicos , Humanos , Animales , Dopamina/metabolismo , Motilidad Gastrointestinal/fisiología , Catecolaminas , InflamaciónRESUMEN
BACKGROUND: Respiratory inflammation is the body's response to lung infection, trauma or hypersensitivity and is often accompanied by comorbidities, including gastrointestinal (GI) symptoms. Why respiratory inflammation is accompanied by GI dysfunction remains unclear. Here, we investigate the effect of lipopolysaccharide (LPS)-induced lung inflammation on intestinal barrier integrity, tight-junctions, enteric neurons and inflammatory marker expression. METHODS: Female C57bl/6 mice (6-8 weeks) were intratracheally administered LPS (5 µg) or sterile saline, and assessed after either 24 or 72 h. Total and differential cell counts in bronchoalveolar lavage fluid (BALF) were used to evaluate lung inflammation. Intestinal barrier integrity was assessed via cross sectional immunohistochemistry of tight junction markers claudin-1, claudin-4 and EpCAM. Changes in the enteric nervous system (ENS) and inflammation in the intestine were quantified immunohistochemically using neuronal markers Hu + and nNOS, glial markers GFAP and S100ß and pan leukocyte marker CD45. RESULTS: Intratracheal LPS significantly increased the number of neutrophils in BALF at 24 and 72 h. These changes were associated with an increase in CD45 + cells in the ileal mucosa at 24 and 72 h, increased goblet cell expression at 24 h, and increased expression of EpCAM at 72 h. LPS had no effect on the expression of GFAP, S100ß, nor the number of Hu + neurons or proportion of nNOS neurons in the myenteric plexus. CONCLUSIONS: Intratracheal LPS administration induces inflammation in the ileum that is associated with enhanced expression of EpCAM, decreased claudin-4 expression and increased goblet cell density, these changes may contribute to systemic inflammation that is known to accompany many inflammatory diseases of the lung.
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Íleon , Inflamación , Neumonía , Animales , Femenino , Ratones , Claudina-4/metabolismo , Estudios Transversales , Molécula de Adhesión Celular Epitelial/metabolismo , Inflamación/inducido químicamente , Inflamación/metabolismo , Lipopolisacáridos/metabolismo , Pulmón/metabolismo , Neumonía/inducido químicamente , Íleon/patologíaRESUMEN
Chemotherapy-induced nausea and vomiting (CINV) is a common side effect of patients with cancer receiving chemotherapeutic drugs. However, the pathological mechanism of CINV is biologically multifaceted and has not yet been fully elucidated. Despite this, increasing evidence indicates that gastrointestinal (GI) inflammation dramatically contributes to the incidence of CINV. It is well established that 5-hydroxytryptamine and substance P are critical meditators in both of CINV and GI inflammation by binding to their corresponding receptors. Meanwhile, antiemetic drugs used for the prophylaxis of CINV have demonstrated surprising effects on relieving GI inflammation, and anti-inflammatory drugs are also effective in preventing CINV. The commonalities between the pathogenesis and clinical treatment of GI inflammation and CINV indicate that GI inflammation is an essential mechanism in CINV. In this review, we provide novel insights into the crucial role of GI inflammation in CINV, with the aim to discover the novel antiemetic drugs against CINV from the perspective of alleviating GI inflammation.
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Antieméticos , Antineoplásicos , Humanos , Antieméticos/farmacología , Antieméticos/uso terapéutico , Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Náusea/prevención & control , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico , Vómitos/prevención & control , Antineoplásicos/efectos adversos , Inflamación/tratamiento farmacológicoRESUMEN
Introduction: Coronavirus disease 2019 (COVID-19) is still causing a global pandemic. But the mechanism of COVID-19 severity is not well elucidated. Materials and methods: We conducted two single-center observational studies of patients with COVID-19. In the first study, the enrolled patients were distinguished based on critical vs. non-critical COVID-19. We collected blood samples from the patients at admission to measure markers related to inflammation and thrombosis and stool samples to analyze the fecal microbiome, metabolome, and calprotectin level. In the second study, we collected ileum and colon tissue samples from patients with critical COVID-19 who required colonoscopy due to severe gastrointestinal symptoms and analyzed mucosal gene expression. Results: A total of 19 blood samples and 10 stool samples were collected. Interleukin (IL)-6 was the only serum inflammatory marker with significantly higher levels in the critical group than in the non-critical group. The fecal calprotectin level in the critical group was significantly higher than that in the non-critical group (P = 0.03), regardless of the presence of gastrointestinal symptoms. Stool metabolomic analysis showed that the level of indole-3-propionic acid, a ligand for aryl hydrocarbon receptor (AhR), was markedly decreased in the critical group compared to that in the non-critical group (P = 0.01). The expression of genes involved in tryptophan metabolism, including ACE2, AHR, CARD9, and IL22, was downregulated in the ileum of critical COVID-19 patients who required a colonoscopy. Discussion: Critical COVID-19 patients have gastrointestinal inflammation potentially caused by impaired tryptophan metabolism in the small intestine due to decreased expression of genes involved in tryptophan metabolism.
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Parkinson's disease (PD) is the second most common neurodegenerative disease attributed to the synergistic effects of genetic risk and environmental stimuli. Although PD is characterized by motor dysfunction resulting from intraneuronal alpha-synuclein accumulations, termed Lewy bodies, and dopaminergic neuronal degeneration in the substantia nigra, multiple systems are involved in the disease process, resulting in heterogenous clinical presentation and progression. Genetic predisposition to PD regarding aberrant immune responses, abnormal protein aggregation, autophagolysosomal impairment, and mitochondrial dysfunction leads to vulnerable neurons that are sensitive to environmental triggers and, together, result in neuronal degeneration. Neuropathology studies have shown that, at least in some patients, Lewy bodies start from the enteric nervous system and then spread to the central dopaminergic neurons through the gut-brain axis, suggesting the contribution of an altered gut microenvironment in the pathogenesis of PD. A plethora of evidence has revealed different gut microbiomes and gut metabolites in patients with PD compared to unaffected controls. Chronic gut inflammation and impaired intestinal barrier integrity have been observed in human PD patients and mouse models of PD. These observations led to the hypothesis that an altered gut microenvironment is a potential trigger of the PD process in a genetically susceptible host. In this review, we will discuss the complex interplay between genetic factors and gut microenvironmental changes contributing to PD pathogenesis.
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Sistema Nervioso Entérico , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Animales , Eje Cerebro-Intestino , Neuronas Dopaminérgicas/metabolismo , Sistema Nervioso Entérico/metabolismo , Sistema Nervioso Entérico/patología , Humanos , Inflamación , Ratones , Enfermedades Neurodegenerativas/patología , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismoRESUMEN
Campylobacter jejuni causes foodborne gastroenteritis and may trigger acute autoimmune sequelae including Guillain Barré Syndrome. Onset of neuromuscular paralysis is associated with exposure to C. jejuni lipooligosaccharide (LOS) classes A, B, C, D, and E that mimic and evoke antibodies against gangliosides on myelin and axons of peripheral nerves. Family members managing a Michigan dairy operation reported recurring C. jejuni gastroenteritis. Because dairy cattle are known to shed C. jejuni, we hypothesized that calves in the sick pen were the source of human infections. Fecal samples obtained from twenty-five calves, one dog, and one asymptomatic family member were cultured for Campylobacter. C. jejuni isolates were obtained from thirteen calves and the family member: C. coli from two calves, and C. hyointestinalis from two calves. Some calves had diarrhea; most were clinically normal. Typing of lipooligosaccharide biosynthetic loci showed that eight calf C. jejuni isolates fell into classes A, B, and C. Two calf isolates and the human isolate possessed LOS class E, associated mainly with enteric disease and rarely with Guillain Barré Syndrome. Multi-locus sequence typing, porA and flaA typing, and whole genome comparisons of the thirteen C. jejuni isolates indicated that the three LOS class E strains that included the human isolate were closely related, indicating zoonotic transmission. Whole-genome comparisons revealed that isolates differed in virulence gene content, particularly in loci encoding biosynthesis of surface structures. Family members experienced diarrheal illness repeatedly over 2 years, yet none experienced GBS despite exposure to calves carrying invasive C. jejuni with LOS known to elicit antiganglioside autoantibodies.
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Chronic inflammatory disease of the gastrointestinal (GI) tract is defined by several pathophysiological characteristics, such as dysbiosis of the microbiota, epithelial barrier hyperpermeability, systemic dissemination of endotoxins and chronic inflammation. In addition to well-reported environmental factors in non-communicable disease, such as smoking, diet, and exercise, humans are frequently exposed to myriads more environmental factors, from pesticides to food additives. Such factors are ubiquitous across both our diet and indoor/outdoor environments. A major route of human exposure to these factors is ingestion, which frequently occurs due to their intentional addition (intentional food additives) and/or unintentional contamination (unintentional food contaminants) of food products-often linked to environmental pollution. Understanding how this persistent, diverse exposure impacts GI health is of paramount importance, as deterioration of the GI barrier is proposed to be the first step towards systemic inflammation and chronic disease. Therefore, we aim to evaluate the impact of ingestion of environmental factors on inflammatory processes in the GI tract. In this review, we highlight human exposure to intentional food additives (e.g. emulsifiers, bulking agents) and unintentional food contaminants (e.g. persistent organic pollutants, pesticides, microplastics), then present evidence for their association with chronic disease, modification of the GI microbiota, increased permeability of the GI barrier, systemic dissemination of endotoxins, local (and distal) pro-inflammatory signalling, and induction of oxidative stress and/or endoplasmic reticulum stress. We also propose a link to NLRP3-inflammasome activation. These findings highlight the contribution of common environmental factors towards deterioration of GI health and the induction of pathophysiology associated with onset and maintenance of chronic inflammation in the GI tract.
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Plaguicidas , Plásticos , Enfermedad Crónica , Endotoxinas , Aditivos Alimentarios , Tracto Gastrointestinal/química , Humanos , Inflamación , Plaguicidas/análisisRESUMEN
The pathogenesis of Androctonus autralis hector (Aah) scorpion venom involved cellular and molecular mechanisms resulting in multi-organ dysfunction. However, little is reported about the effects of venom on the gastrointestinal axis. Mast cells (MCs) are known to play a crucial role in modulating immune response of the gut. This study aims to investigate the involvement of this cell type in venom-induced gastric and intestinal disorders in a time course (3 and 24h). The obtained results revealed that Aah scorpion venom induced inflammatory cell infiltration as shown by the increase of the myeloperoxidase and eosinophil peroxidase activities. Overexpression of the c-kit receptor (CD117) severely imbalanced the redox status with depletion of antioxidant systemic accompanied by gastrointestinal tissue damage. Moreover, an increased level of lactate dehydrogenase in the serum was correlated with tissue injuries. Pharmacological inhibition of MCs targeting tyrosine kinase (TK) reduces the generation of reactive oxygen species and normalizes catalase, and gluthation S-transferase activities to their physiological levels. In addition, histopathological alterations were restored after pretreatment with c-kit receptor inhibitor associated with a considerable reduction of MC density. Interestingly, obtained results indicate that MCs might be involved in gastric modulation and intestinal inflammation through c-kit signaling following sub-cutaneous Aah venom injection.
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Mastocitos , Venenos de Escorpión , Tracto Gastrointestinal , Inmunidad , Oxidación-Reducción , Venenos de Escorpión/farmacologíaRESUMEN
Neurotransmitters are special molecules that serve as messengers in chemical synapses between neurons, cells, or receptors, including catecholamines, serotonin, dopamine, and other neurotransmitters, which play an important role in both human physiology and pathology. Compelling evidence has indicated that neurotransmitters have an important physiological role in various digestive diseases. They act as ligands in combination with central or peripheral receptors, and transmits signals through chemical synapses, which are involved in regulating the physiological and pathological processes of the digestive tract organs. For instance, neurotransmitters regulate blood circulation and affect intestinal movement, nutrient absorption, the gastrointestinal innate immune system, and the microbiome. In this review, we will focus on the role of neurotransmitters in the pathogenesis of digestive tract diseases to provide novel therapeutic targets for new drug development in digestive diseases.
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Early exposure to Enterobacteriaceae may result in inappropriate microbial colonization of the gastrointestinal (GI) tract, induce mild GI inflammation, alter immune system development, and predispose poultry to opportunistic infection. Four experiments were conducted to test Enterobacteriaceae isolates Escherichia coli LG strain (LG), E. coli Huff strain (Huff), Salmonella Enteritidis LB (SE) and Salmonella Typhimurium (ST) on ability to induce GI inflammation. All 4 experiments included a noninoculated control, and day of hatch (DOH) oral inoculation of LG, Huff, SE and ST in experiment 1, LG and SE in experiment 2, and LG, Huff, SE, and ST in experiment 3. Experiment 4 included LG, Huff, a noninoculated control (NIC), and Clostridium perfringens only (NCP) wherein birds received oral C. perfringens challenge on d15-16 to induce necrotic enteritis. Body weight was measured, yolk sacs and spleens were collected, and blood was obtained for serum fluorescein isothiocyanate dextran (FITC-d) recovery and alpha-1-acid glycoprotein (A1GP) concentrations. Samples were taken weekly through 2 wk of age in experiments 1 and 2, or 4 wk of age in experiments 3 and 4. Increased FITC-d recovery was observed for LG and SE on d13 in experiment 2 (P < 0.05), and C. perfringens only birds on d27 in experiment 4 (P < 0.05) as compared to noninoculated controls. Each experiment resulted in notable differences in A1GP serum concentrations over time, with fluctuations in A1GP patterns through d14 based on DOH inoculation (P < 0.05). Over time, A1GP was increased for DOH inoculated birds from d 22 to 29, the fourth wk of life, and d 2-29, the entire experiment, vs. noninoculated controls in experiment 3 (P < 0.05). Similarly, NCP and LGCP showed increased A1GP from d 20 to 27 and d 6 to 27, vs. NIC in experiment 4 (P < 0.05). In experiment 4, C. perfringens challenge resulted in earlier A1GP response in DOH inoculated birds, d 17-20, as compared to NCP birds, d 20-27 (P < 0.05). These results suggest early Enterobacteriaceae exposure may influence early inflammatory state in the GI tract and may also alter patterns of inflammation and responsiveness to pathogens.
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Infecciones por Clostridium , Enfermedades de las Aves de Corral , Animales , Pollos , Infecciones por Clostridium/veterinaria , Clostridium perfringens , Enterobacteriaceae , Escherichia coli , Inflamación/veterinaria , PermeabilidadRESUMEN
Inappropriate microbial colonization can induce gastrointestinal (GI) inflammation may predispose poultry to opportunistic infections and reduce growth performance. Four independent experiments were completed to test ability of select Enterobacteriaceae isolates to induce GI inflammation. Experiments 1 and 2 included a non-inoculated control (NC), and a low (L), medium (M), or high (H) day of hatch (DOH) oral inoculation level. In experiment 1, birds in L1, M1, and H1 received 102 to 104 CFU of a mixed dose of 2 species of Citrobacter and Salmonella Enteritidis LB (SE). In experiment 2, birds in L2, M2, and H2 received 103 to 105 CFU of E. coli LG (LG) and included NC. Body weight was recorded on d 0, 7, and 14, with blood collected for chicken serum alpha-1-acid glycoprotein (A1GP) measurements on d14. Neither experiment resulted in differences in BWG, however, A1GP was increased (P < 0.05) on d 14 when DOH inoculation dose 103 CFU/chick was used compared to NC. This observed increase in A1GP resulted in selection of 103 CFU/chick for DOH inoculation in experiments 3 and 4. Experiment 3 consisted of NC, E. coli Huff (Huff), and SE. On d 0, 7 and 15, BW was measured, with blood collected on d 15 for A1GP. Both d 15 A1GP and BWG from d 7 to 15 were reduced in inoculated chicks, Huff and SE, in experiment 3 (P < 0.05). Experiment 4 evaluated NC and LG with BW measured on d 0, 2, 7 and 14. Yolk sacs were evaluated for retention and bacterial enumeration, and blood for serum A1GP were collected on d 2 and 14. Experiment 4 resulted in no differences in yolk sac parameters or A1GP, whereas there was an increase in BWG for LG from d 0 to 14 (P < 0.05). When evaluated over time, serum A1GP increased between d 2 and d 14 by nearly 46% in LG, compared to negligible changes in NC (P = 0.111). Mild GI inflammation induced by early Enterobacteriaceae exposure may not drastically impact growth or inflammation parameters but may increase susceptibility to opportunistic infection necessitating further study of this model.