RESUMEN
BACKGROUND: The aim of this study is to investigate the altered composition of fecal microbiota, organic acids, and the effect of probiotics in the guinea pig model of the postoperative ileus (POI). METHODS: A laparotomy with cecal manipulation was performed to induce POI in guinea pigs. Fecal pellets were collected before the operation (the baseline) and 1, 3, and 5 days after the operation. The extracted fecal DNA was amplified and sequenced using the Illumina MiSeq sequencing system. The same POI procedures were performed after oral pretreatment of the probiotics for 7 days before operation. The effect of the probiotics on the selected taxa and fecal acetate were evaluated, as were the butyrate levels. The colonic transit was assessed by measurement of the fecal pellet output. KEY RESULTS: The communities of the baseline and POI groups indicated significantly distinct composition. The genera Bifidobacterium and Lactobacillus were more abundant in the baseline group compared with the POI groups, and Bacteroides and Blautia were more abundant in the POI groups. Decreased abundances of the species Bifidobacterium bifidum and Bifidobacterium longum after the POI procedure were significantly increased in the probiotics group. The decreased fecal butyrate level after the POI procedure was significantly increased, and colonic transit was significantly improved in the probiotics group. CONCLUSIONS AND INFERENCES: POI induces gut bacterial dysbiosis. Moreover, pretreatment of probiotics before operation restores the beneficial bacterial species, butyrate production, and bowel movement. The modulation of gut microbiota may help the treatment and prevention of POI.
Asunto(s)
Disbiosis/microbiología , Microbioma Gastrointestinal , Ileus/microbiología , Complicaciones Posoperatorias/microbiología , Probióticos , Acetatos/metabolismo , Animales , Bacteroides , Bifidobacterium , Butiratos/metabolismo , Clostridiales , Modelos Animales de Enfermedad , Disbiosis/metabolismo , Heces/química , Heces/microbiología , Cobayas , Ileus/metabolismo , Lactobacillus , Complicaciones Posoperatorias/metabolismo , Cuidados PreoperatoriosRESUMEN
AIM: To explore the effects of abdominal surgery and interleukin-1 signaling on antimicrobial defense in a model of postoperative ileus. METHODS: C57BL/6 and Interleukin-1 receptor type I (IL-1R1) deficient mice underwent intestinal manipulation to induce POI. Expression of mucosal IL-1α, IL-1ß and IL-1R1 and several antimicrobial peptides and enzymes were measured by quantitative PCR or ELISA, western blotting or immunohistochemistry. Bacterial overgrowth was determined by fluorescent in-situ hybridization and counting of jejunal luminal bacteria. Translocation of aerobic and anaerobic bacteria into the intestinal wall, mesenteric lymph nodes, liver and spleen was determined by counting bacterial colonies on agar plates 48h after plating of tissue homogenates. Antimicrobial activity against E. coli and B. vulgatus was analyzed in total and cationic fractions of small bowel mucosal tissue homogenates by a flow cytometry-based bacterial depolarization assay. RESULTS: Jejunal bacterial overgrowth was detected 24h after surgery. At the same time point, but not in the early phase 3h after surgery, bacterial translocation into the liver and mesenteric lymph nodes was observed. Increased antimicrobial activity against E. coli was induced within early phase of POI. Basal antimicrobial peptide and enzyme gene expression was higher in the ileal compared to the jejunal mucosa. The expression of lysozyme 1, cryptdin 1, cryptdin 4 and mucin 2 were reduced 24h after surgery in the ileal mucosa and mucin 2 was also reduced in the jejunum. Postoperative IL-1α and IL-1ß were increased in the postoperative mucosa. Deficiency of IL-1R1 affected the expression of antimicrobial peptides during homeostasis and POI. CONCLUSION: Small bowel antimicrobial capacity is disturbed during POI which is accompanied by bacterial overgrowth and translocation. IL-1R1 is partially involved in the gene expression of mucosal antimicrobial peptides. Altered small bowel antimicrobial activity may contribute also to POI development and manifestation in patients undergoing abdominal surgery.
Asunto(s)
Ileus/microbiología , Mucosa Intestinal/microbiología , Complicaciones Posoperatorias/microbiología , Animales , Modelos Animales de Enfermedad , Ileus/metabolismo , Ileus/patología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , Ratones , Complicaciones Posoperatorias/metabolismo , Complicaciones Posoperatorias/patología , Receptores Tipo I de Interleucina-1/metabolismo , Transducción de SeñalRESUMEN
OBJECTIVE: Postoperative ileus (POI), the most frequent complication after intestinal surgery, depends on dendritic cells (DCs) and macrophages. Here, we have investigated the mechanism that activates these cells and the contribution of the intestinal microbiota for POI induction. DESIGN: POI was induced by manipulating the intestine of mice, which selectively lack DCs, monocytes or macrophages. The disease severity in the small and large intestine was analysed by determining the distribution of orally applied fluorescein isothiocyanate-dextran and by measuring the excretion time of a retrogradely inserted glass ball. The impact of the microbiota on intestinal peristalsis was evaluated after oral antibiotic treatment. RESULTS: We found that Cd11c-Cre+ Irf4flox/flox mice lack CD103+CD11b+ DCs, a DC subset unique to the intestine whose function is poorly understood. Their absence in the intestinal muscularis reduced pathogenic inducible nitric oxide synthase (iNOS) production by monocytes and macrophages and ameliorated POI. Pathogenic iNOS was produced in the jejunum by resident Ly6C- macrophages and infiltrating chemokine receptor 2-dependent Ly6C+ monocytes, but in the colon only by the latter demonstrating differential tolerance mechanisms along the intestinal tract. Consistently, depletion of both cell subsets reduced small intestinal POI, whereas the depletion of Ly6C+ monocytes alone was sufficient to prevent large intestinal POI. The differential role of monocytes and macrophages in small and large intestinal POI suggested a potential role of the intestinal microbiota. Indeed, antibiotic treatment reduced iNOS levels and ameliorated POI. CONCLUSIONS: Our findings reveal that CD103+CD11b+ DCs and the intestinal microbiome are a prerequisite for the activation of intestinal monocytes and macrophages and for dysregulating intestinal motility in POI.
Asunto(s)
Células Dendríticas/citología , Microbioma Gastrointestinal , Ileus/inmunología , Ileus/microbiología , Activación de Macrófagos , Monocitos/inmunología , Peristaltismo/inmunología , Complicaciones Posoperatorias/inmunología , Complicaciones Posoperatorias/microbiología , Animales , Antígenos CD/inmunología , Antígeno CD11b/inmunología , Modelos Animales de Enfermedad , Tránsito Gastrointestinal , Ileus/fisiopatología , Cadenas alfa de Integrinas/inmunología , Ratones , Ratones Transgénicos , Complicaciones Posoperatorias/fisiopatologíaRESUMEN
BACKGROUND: Since the very early days of surgical practice, surgeons have recognized the importance of considering that intestinal microbes might have a profound influence on recovery from surgical diseases such as appendicitis and peritonitis. Although the pathogenesis of surgical diseases such as cholelithiasis, diverticulosis, peptic ulcer disease and cancer have been viewed as disorders of host biology, they are emerging as diseases highly influenced by their surrounding microbiota. METHODS: This is a review of evolving concepts in microbiome sciences across a variety of surgical diseases and disorders, with a focus on disease aetiology and treatment options. RESULTS: The discovery that peptic ulcer disease and, in some instances, gastric cancer can now be considered as infectious diseases means that to advance surgical practice humans need to be viewed as superorganisms, consisting of both host and microbial genes. Applying this line of reasoning to the ever-ageing population of patients demands a more complete understanding of the effects of modern-day stressors on both the host metabolome and microbiome. CONCLUSION: Despite major advances in perioperative care, surgeons today are witnessing rising infection-related complications following elective surgery. Many of these infections are caused by resistant and virulent micro-organisms that have emerged as a result of human progress, including global travel, antibiotic exposure, crowded urban conditions, and the application of invasive and prolonged medical and surgical treatment. A more complete understanding of the role of the microbiome in surgical disease is warranted to inform the path forward for prevention.
Asunto(s)
Microbioma Gastrointestinal , Infección de la Herida Quirúrgica/microbiología , Infección de la Herida Quirúrgica/prevención & control , Inmunidad Adaptativa , Fuga Anastomótica/microbiología , Humanos , Ileus/microbiología , Inmunidad Innata , Fenómenos Fisiológicos de la Nutrición , Sepsis/microbiología , Cicatrización de HeridasRESUMEN
UNLABELLED: Acute brain ischemia induces a local neuroinflammatory reaction and alters peripheral immune homeostasis at the same time. Recent evidence has suggested a key role of the gut microbiota in autoimmune diseases by modulating immune homeostasis. Therefore, we investigated the mechanistic link among acute brain ischemia, microbiota alterations, and the immune response after brain injury. Using two distinct models of acute middle cerebral artery occlusion, we show by next-generation sequencing that large stroke lesions cause gut microbiota dysbiosis, which in turn affects stroke outcome via immune-mediated mechanisms. Reduced species diversity and bacterial overgrowth of bacteroidetes were identified as hallmarks of poststroke dysbiosis, which was associated with intestinal barrier dysfunction and reduced intestinal motility as determined by in vivo intestinal bolus tracking. Recolonizing germ-free mice with dysbiotic poststroke microbiota exacerbates lesion volume and functional deficits after experimental stroke compared with the recolonization with a normal control microbiota. In addition, recolonization of mice with a dysbiotic microbiome induces a proinflammatory T-cell polarization in the intestinal immune compartment and in the ischemic brain. Using in vivo cell-tracking studies, we demonstrate the migration of intestinal lymphocytes to the ischemic brain. Therapeutic transplantation of fecal microbiota normalizes brain lesion-induced dysbiosis and improves stroke outcome. These results support a novel mechanism in which the gut microbiome is a target of stroke-induced systemic alterations and an effector with substantial impact on stroke outcome. SIGNIFICANCE STATEMENT: We have identified a bidirectional communication along the brain-gut microbiota-immune axis and show that the gut microbiota is a central regulator of immune homeostasis. Acute brain lesions induced dysbiosis of the microbiome and, in turn, changes in the gut microbiota affected neuroinflammatory and functional outcome after brain injury. The microbiota impact on immunity and stroke outcome was transmissible by microbiota transplantation. Our findings support an emerging concept in which the gut microbiota is a key regulator in priming the neuroinflammatory response to brain injury. These findings highlight the key role of microbiota as a potential therapeutic target to protect brain function after injury.
Asunto(s)
Disbiosis/etiología , Encefalitis/complicaciones , Encefalitis/etiología , Microbiota/fisiología , Accidente Cerebrovascular/complicaciones , Animales , Infarto Encefálico/etiología , Complejo CD3/metabolismo , Modelos Animales de Enfermedad , Disbiosis/inmunología , Disbiosis/microbiología , Heces/microbiología , Femenino , Enfermedades Gastrointestinales/etiología , Motilidad Gastrointestinal/fisiología , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Ileus/inmunología , Ileus/microbiología , Ileus/patología , Infarto de la Arteria Cerebral Media/complicaciones , Leucocitos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microbiota/inmunología , Accidente Cerebrovascular/etiología , Estructuras Linfoides Terciarias/patologíaRESUMEN
A human gut-on-a-chip microdevice was used to coculture multiple commensal microbes in contact with living human intestinal epithelial cells for more than a week in vitro and to analyze how gut microbiome, inflammatory cells, and peristalsis-associated mechanical deformations independently contribute to intestinal bacterial overgrowth and inflammation. This in vitro model replicated results from past animal and human studies, including demonstration that probiotic and antibiotic therapies can suppress villus injury induced by pathogenic bacteria. By ceasing peristalsis-like motions while maintaining luminal flow, lack of epithelial deformation was shown to trigger bacterial overgrowth similar to that observed in patients with ileus and inflammatory bowel disease. Analysis of intestinal inflammation on-chip revealed that immune cells and lipopolysaccharide endotoxin together stimulate epithelial cells to produce four proinflammatory cytokines (IL-8, IL-6, IL-1ß, and TNF-α) that are necessary and sufficient to induce villus injury and compromise intestinal barrier function. Thus, this human gut-on-a-chip can be used to analyze contributions of microbiome to intestinal pathophysiology and dissect disease mechanisms in a controlled manner that is not possible using existing in vitro systems or animal models.
Asunto(s)
Enfermedades Inflamatorias del Intestino/microbiología , Enfermedades Inflamatorias del Intestino/fisiopatología , Mucosa Intestinal/microbiología , Mucosa Intestinal/fisiopatología , Dispositivos Laboratorio en un Chip , Microbiota/fisiología , Modelos Biológicos , Peristaltismo/fisiología , Animales , Antibacterianos/uso terapéutico , Bacterias/crecimiento & desarrollo , Células CACO-2 , Humanos , Ileus/tratamiento farmacológico , Ileus/microbiología , Ileus/fisiopatología , Técnicas In Vitro , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Interleucina-1beta/inmunología , Interleucina-6/inmunología , Interleucina-8/inmunología , Mucosa Intestinal/efectos de los fármacos , Peristaltismo/efectos de los fármacos , Probióticos/uso terapéutico , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
In experiment, while simulating an acute ileus, the possibility of antibacterial preparations for prophylaxis of purulent--septic complications was studied. There was established, that while progressing purulent intestinal inflammation its wall already in 12 h losses a capacity to cumulate penicillines and aminoglycosides. In a phlegmon-like changed intestine during 48 h cephalosporins and fluorochinolons are accumulated in bactericidal concentration, making a destruction of intestinal wall and occurrence of purulent peritonitis by 6-12 h slower.
Asunto(s)
Antibacterianos/farmacología , Ileus/tratamiento farmacológico , Peritonitis/prevención & control , Ampicilina/farmacocinética , Ampicilina/farmacología , Animales , Antibacterianos/farmacocinética , Transporte Biológico , Cefalosporinas/farmacocinética , Cefalosporinas/farmacología , Ciprofloxacina/análogos & derivados , Modelos Animales de Enfermedad , Fluoroquinolonas/farmacocinética , Fluoroquinolonas/farmacología , Gentamicinas/farmacocinética , Gentamicinas/farmacología , Ileus/complicaciones , Ileus/microbiología , Ileus/patología , Peritonitis/etiología , Peritonitis/microbiología , Peritonitis/patología , Permeabilidad , Ratas , Ratas WistarRESUMEN
In experiment on the model of mechanical acute ileus (AI) in accordance to morphological and microbiological investigations data there was established, that in intestinal wall, situated above the obstacle place, purulent enteritis occurs, what may constitute the origin of purulent-septic complications after elimination of the Al cause. Application of antibacterial preparations permits to slow down the progression of destructive processes in the affected intestinal wall.
Asunto(s)
Antibacterianos/farmacología , Ileítis/tratamiento farmacológico , Íleon/efectos de los fármacos , Ileus/tratamiento farmacológico , Ampicilina/farmacología , Animales , Bacterias/efectos de los fármacos , Bacterias/crecimiento & desarrollo , Bacterias/aislamiento & purificación , Ceftriaxona/farmacología , Ciprofloxacina/análogos & derivados , Fluoroquinolonas/farmacología , Gentamicinas/farmacología , Ileítis/microbiología , Ileítis/patología , Íleon/microbiología , Íleon/patología , Ileus/microbiología , Ileus/patología , Inyecciones Intramusculares , Pruebas de Sensibilidad Microbiana , Ratas , Ratas WistarRESUMEN
Results of complex treatment of patients, suffering acute small intestinal ileus, using early enteral therapy via probe, were presented.
Asunto(s)
Ileus/cirugía , Intestino Delgado/cirugía , Intubación Gastrointestinal/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enterobacteriaceae/crecimiento & desarrollo , Femenino , Humanos , Ileus/microbiología , Ileus/patología , Ileus/terapia , Intestino Delgado/microbiología , Intestino Delgado/patología , Intubación Gastrointestinal/instrumentación , Tiempo de Internación , Masculino , Persona de Mediana Edad , Recuperación de la FunciónRESUMEN
For the diagnosis of Clostridium difficile infection (CDI), it is necessary to obtain microbiological evidence of toxigenic C. difficile with a compatible clinical picture (diarrhoea or ileus). Two gold standards exist: cell culture cytotoxicity neutralization assay (specific, but less sensitive than previously acknowledged) and toxigenic culture (very sensitive but less specific because it also detects asymptomatic colonization). These gold standards are not used routinely because at least 2 or 3 days are needed to get a definitive result. Enzyme immunoassays (EIA) are used by most of the French laboratories for the detection of toxins A and B: they provide a quick answer but their sensitivity is insufficient (only 50%). Molecular assays (targeting tcdA or tcdB genes) and glutamate dehydrogenase (GDH) EIA represent an attractive alternative because their high sensitivity (>85%) allow to definitely rule out CDI in the case of a negative result. The presence of GDH is not specific of toxigenic C. difficile: positive results must be confirmed by another method. In the event of a positive molecular assay without toxin presence assessed by EIA or cytotoxicity assay, other causes of diarrhoea should be ruled out before a definitive diagnosis of CDI can be made.
Asunto(s)
Técnicas de Laboratorio Clínico/métodos , Clostridioides difficile/aislamiento & purificación , Enterocolitis Seudomembranosa/diagnóstico , Toxinas Bacterianas/análisis , Pruebas Inmunológicas de Citotoxicidad , Diarrea/microbiología , Humanos , Ileus/microbiología , Técnicas para Inmunoenzimas , Técnicas de Diagnóstico Molecular , Pruebas de NeutralizaciónRESUMEN
We report on the case of a segmentally emphasised, ulcerous chronic haemorrhagic colitis with the development of granulation tissue und scarred fibrosis with consecutive resulting stenosis of the colon. A 49-year-old male patient was infected with enterohaemorrhagic Escherichia coli bacteria during the EHEC-epidemic in northern Germany in early summer 2011. In the course of the infection the patient suffered from haemolytic uraemic syndrome (HUS) with acute renal failure and neurological symptoms. Haemodialysis and plasmapheresis had become mandatory. A simultaneous ileus was estimated to be of paralytic origin. One month after treatment of the acute phase of the infection a CT scan of the abdomen was performed and discovered a symptomatic stenosis of the proximal colon transversum. This obstruction needed to be treated by performing a right hemicolectomy with an ileo-transverso anastomosis. After surgery the patient recovered continuously. The histopathological examination verified an ulcerous-chronic haemorrhagic colitis on the background of an EHEC infection.
Asunto(s)
Colitis/microbiología , Enfermedades del Colon/microbiología , Escherichia coli Enterohemorrágica/aislamiento & purificación , Infecciones por Escherichia coli/microbiología , Hemorragia Gastrointestinal/microbiología , Obstrucción Intestinal/microbiología , Úlcera/microbiología , Humanos , Ileus/microbiología , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Pneumonic tularemia is caused by inhalation of the gram negative bacterium, Francisella tularensis. Because of concerns that tularemia could be used as a bioterrorism agent, vaccines and therapeutics are urgently needed. Animal models of pneumonic tularemia with a pathophysiology similar to the human disease are needed to evaluate the efficacy of these potential medical countermeasures. PRINCIPAL FINDINGS: Rabbits exposed to aerosols containing Francisella tularensis strain SCHU S4 developed a rapidly progressive fatal pneumonic disease. Clinical signs became evident on the third day after exposure with development of a fever (>40.5°C) and a sharp decline in both food and water intake. Blood samples collected on day 4 found lymphopenia and a decrease in platelet counts coupled with elevations in erythrocyte sedimentation rate, alanine aminotransferase, cholesterol, granulocytes and monocytes. Radiographs demonstrated the development of pneumonia and abnormalities of intestinal gas consistent with ileus. On average, rabbits were moribund 5.1 days after exposure; no rabbits survived exposure at any dose (190-54,000 cfu). Gross evaluation of tissues taken at necropsy showed evidence of pathology in the lungs, spleen, liver, kidney and intestines. Bacterial counts confirmed bacterial dissemination from the lungs to the liver and spleen. CONCLUSIONS/SIGNIFICANCE: The pathophysiology of pneumonic tularemia in rabbits resembles what has been reported for humans. Rabbits therefore are a relevant model of the human disease caused by type A strains of F. tularensis.
Asunto(s)
Neumonía/diagnóstico por imagen , Neumonía/microbiología , Tularemia/diagnóstico por imagen , Tularemia/microbiología , Animales , Antígenos CD13/sangre , Ingestión de Alimentos , Humanos , Ileus/microbiología , Intestinos/microbiología , Riñón/microbiología , Hígado/microbiología , Pulmón/microbiología , Linfopenia/microbiología , Recuento de Plaquetas , Neumonía/sangre , Conejos , Radiografía , Bazo/microbiología , Tularemia/sangreRESUMEN
BACKGROUND: 'Intestinal tuberculosis' is sometimes difficult to diagnose. The symptoms are non-specific and there is an extensive differential diagnosis. CASE DESCRIPTION: A 27-year-old man from Pakistan presented at the emergency department with a history of constipation, weight loss and abdominal pain. An abdominal CT scan revealed dilated small bowel loops, lymphadenopathy and a thickened intestinal wall of the terminal ileum. Cultures of a cervical lymph node biopsy tested positive for Mycobacterium tuberculosis: intestinal tuberculosis. The man eventually recovered after treatment with tuberculostatics. CONCLUSION: The most sensitive methods for establishing the diagnosis 'intestinal tuberculosis' are an abdominal CT scan and a colonoscopy with ileal and colonic biopsies; establishing the diagnosis can be challenging as a result of non-specific test results.
Asunto(s)
Antituberculosos/uso terapéutico , Ileus/diagnóstico , Ileus/etiología , Tuberculosis Gastrointestinal/complicaciones , Tuberculosis Gastrointestinal/tratamiento farmacológico , Adulto , Diagnóstico Diferencial , Humanos , Ileus/tratamiento farmacológico , Ileus/microbiología , Masculino , Resultado del Tratamiento , Tuberculosis Gastrointestinal/diagnóstico , Tuberculosis Ganglionar/complicaciones , Tuberculosis Ganglionar/diagnóstico , Tuberculosis Ganglionar/tratamiento farmacológicoRESUMEN
Mycobacterium genavense (M genavense) has been recognized as a life-threatening pathogen in severely immunocompromised patients. To our knowledge, disseminated M genavense infection has never been described in immunocompetent individuals. Here, we report a case of disseminated M genavense infection in a healthy Japanese boy. A 15-year-old boy who had never been diagnosed with an immunodeficiency disorder was hospitalized because of ileus. Tumorous lesions were identified in the ileum, cecum, and ascending colon, resulting in stenosis of ileocecal valve. There was diffuse proliferation of histiocytes throughout the intestinal wall, along with lymphocytic infiltration. No nuclear or cellular atypia was present in these cells. Ziehl-Neelsen staining revealed numerous acid-fast bacteria in histiocytes. After surgery, systemic lymph node swelling was noticed by generalized examination, including the mesenteric and cervical lymph nodes. M genavense DNA was identified by direct sequencing of 16S ribosomal DNA that had been amplified by polymerase chain reaction.
Asunto(s)
Enfermedades Intestinales/microbiología , Ganglios Linfáticos/microbiología , Infecciones por Mycobacterium/microbiología , Mycobacterium/aislamiento & purificación , Adolescente , Antibacterianos/uso terapéutico , ADN Bacteriano/análisis , Quimioterapia Combinada , Histiocitos/microbiología , Histiocitos/patología , Humanos , Ileus/microbiología , Ileus/patología , Ileus/cirugía , Inmunocompetencia , Enfermedades Intestinales/diagnóstico , Enfermedades Intestinales/terapia , Ganglios Linfáticos/patología , Masculino , Mycobacterium/genética , Infecciones por Mycobacterium/diagnóstico , Infecciones por Mycobacterium/terapia , ARN Ribosómico 16S/análisis , Resultado del TratamientoRESUMEN
Endotoxemia by bacterial lipopolysaccharide (LPS) has been reported to affect gut motility specifically depending on Toll-like receptor 4 activation (TLR4). However, the direct impact of LPS ligation to TLR4 on human smooth muscle cells (HSMC) activity still remains to be elucidated. The present study shows that TLR4, its associated molecule MD2, and TLR2 are constitutively expressed on cultured HSMC and that, once activated, they impair HSMC function. The stimulation of TLR4 by LPS induced a time- and dose-dependent contractile dysfunction, which was associated with a decrease of TLR2 messenger, a rearrangement of microfilament cytoskeleton and an oxidative imbalance, i.e., the formation of reactive oxygen species (ROS) together with the depletion of GSH content. An alteration of mitochondria, namely a hyperpolarization of their membrane potential, was also detected. Most of these effects were partially prevented by the NADPH oxidase inhibitor apocynin or the NFkappaB inhibitor MG132. Finally, a 24 h washout in LPS-free medium almost completely restored morphofunctional and biochemical HSMC resting parameters, even if GSH levels remained significantly lower and no recovery was observed in TLR2 expression. Thus, the exposure to bacterial endotoxin directly and persistently impaired gastrointestinal smooth muscle activity indicating that HSMC actively participate to dysmotility during infective burst. The knowledge of these interactions might provide novel information on the pathogenesis of infection-associated gut dysmotility and further clues for the development of new therapeutic strategies.
Asunto(s)
Colitis/complicaciones , Colon/metabolismo , Motilidad Gastrointestinal/fisiología , Ileus/microbiología , Miocitos del Músculo Liso/metabolismo , Receptor Toll-Like 4/metabolismo , Células Cultivadas , Colitis/fisiopatología , Colon/citología , Colon/fisiopatología , Relación Dosis-Respuesta a Droga , Endotoxemia/inducido químicamente , Endotoxemia/fisiopatología , Motilidad Gastrointestinal/efectos de los fármacos , Humanos , Ileus/fisiopatología , Mediadores de Inflamación/farmacología , Lipopolisacáridos/farmacología , Antígeno 96 de los Linfocitos/efectos de los fármacos , Antígeno 96 de los Linfocitos/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/fisiología , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Receptor Toll-Like 2/efectos de los fármacos , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/efectos de los fármacosAsunto(s)
Ileus/complicaciones , Ileus/etiología , Complicaciones Posoperatorias/etiología , Enfermedad Aguda , Animales , Humanos , Ileus/microbiología , Ileus/mortalidad , Ileus/patología , Ileus/cirugía , Intestinos/irrigación sanguínea , Intestinos/microbiología , Intestinos/patología , Intestinos/cirugía , Complicaciones Posoperatorias/mortalidadRESUMEN
Highly inducible heme oxygenase (HO)-1 is protective against acute and chronic inflammation. HO-1 generates carbon monoxide (CO), ferrous iron, and biliverdin. The aim of this study was to investigate the protective effects of biliverdin against sepsis-induced inflammation and intestinal dysmotility. Cecal ligation and puncture (CLP) was performed on Sprague-Dawley rats under isoflurane anesthesia with and without intraperitoneal biliverdin injections, which were done before, at the time of CLP, and after CLP. In vivo gastrointestinal transit was carried out with fluorescein-labeled dextran. Jejunal circular muscle contractility was quantified in vitro using organ bath-generated bethanechol dose-response curves. Neutrophilic infiltration into the muscularis externa was quantified. The jejunal muscularis was studied for cytokine mRNA expressions [interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, inducible nitric oxide synthase, cyclooxygenase-2, biliverdin, IL-10, and HO-1] using real-time RT-PCR. Biliverdin treatment prevented the sepsis-induced suppression of gastrointestinal muscle contractility in vivo and in vitro and significantly decreased neutrophilic infiltration into the jejunal muscularis. Inflammatory mRNA expressions for small bowel IL-6 and MCP-1 were significantly reduced after biliverdin treatment in CLP-induced septic animals compared with untreated septic animals. The anti-inflammatory mediator expression of small bowel IL-10 was significantly augmented after CLP at 3 h compared with untreated septic animals. These findings demonstrate that biliverdin attenuates sepsis-induced morbidity to the intestine by selectively modulating the inflammatory cascade and its subsequent sequelae on intestinal muscularis function.
Asunto(s)
Biliverdina/administración & dosificación , Motilidad Gastrointestinal/inmunología , Ileus/inmunología , Ileus/prevención & control , Mediadores de Inflamación/inmunología , Sepsis/inmunología , Sepsis/prevención & control , Animales , Gastroenteritis/inmunología , Gastroenteritis/microbiología , Gastroenteritis/prevención & control , Motilidad Gastrointestinal/efectos de los fármacos , Ileus/microbiología , Inyecciones Intraperitoneales , Masculino , Membrana Mucosa/inmunología , Membrana Mucosa/microbiología , Ratas , Ratas Sprague-Dawley , Sepsis/microbiología , Resultado del TratamientoRESUMEN
Ghrelin is an orexigenic peptide with prokinetic effects in the rat. We investigated the effect of ghrelin and growth hormone-releasing hormone 6 (GHRP-6) on gastric emptying and transit in control and septic mice. Mice were injected i.p. with lipopolysaccharides (LPS) or saline (control). After 16-17 h mice were pretreated with saline, ghrelin or GHRP-6 1 h before intragastric administration of Evans blue. Fifteen minutes later, after assessment of the behaviour scale, mice were killed and gastric emptying, transit and rectal temperature were measured. In control mice, ghrelin (100 microg kg(-1)) and GHRP-6 (20-100 microg kg(-1)) accelerated gastric emptying, whereas ghrelin and GHRP-6 failed to increase transit significantly. Septic mice developed a delay in gastric emptying and transit, hypothermia and a deterioration of the behaviour scale. In septic mice, ghrelin (20 microg kg(-1)) accelerated gastric emptying without effect on transit while GHRP-6 significantly accelerated gastric emptying dose-dependently and failed to increase transit significantly. Ghrelin and GHRP-6 had no effect on the endotoxin-induced hypothermia or deterioration of behaviour scale. Therefore, the beneficial prokinetic effect of ghrelin but mainly of GHRP-6 offers potential therapeutic options in the treatment of septic gastric ileus.
Asunto(s)
Ileus/tratamiento farmacológico , Oligopéptidos/uso terapéutico , Hormonas Peptídicas/uso terapéutico , Sepsis/tratamiento farmacológico , Animales , Vaciamiento Gástrico/efectos de los fármacos , Vaciamiento Gástrico/fisiología , Ghrelina , Ileus/microbiología , Masculino , Ratones , Oligopéptidos/farmacología , Hormonas Peptídicas/farmacología , Sepsis/microbiologíaRESUMEN
Sepsis frequently occurs after hemorrhage, trauma, burn, or abdominal surgery and is a leading cause of morbidity and mortality in severely ill patients. We performed experiments to delineate intestinal molecular and functional motility consequences of polymicrobial sepsis in the clinically relevant cecal ligation and puncture (CLP) sepsis model. CLP was performed on male Sprague-Dawley rats. Gastrointestinal transit, colonic in vivo pressure recordings, and in vitro muscle contractions were recorded. Histochemistry was performed for macrophages, monocytes, and neutrophils. Inflammatory gene expressions were quantified by real-time RT-PCR. CLP delayed gastrointestinal transit, decreased colonic pressures, and suppressed in vivo circular muscle contractility of the jejunum and colon over a 4-day period. A leukocytic infiltrate of monocytes and neutrophils developed over 24 h. Real-time RT-PCR demonstrated a significant temporal elevation in IL-6, IL-1beta, monocyte chemoattractant protein-1, and inducible nitric oxide synthase, with higher expression levels of IL-6 and inducible nitric oxide synthase in colonic extracts compared with small intestine. Polymicrobial CLP sepsis induces a complex inflammatory response within the intestinal muscularis with the recruitment of leukocytes and elaboration of mediators that inhibit intestinal muscle function. Differences were elucidated between endotoxin and CLP models of sepsis, as well as a heterogeneous regional response of the gastrointestinal tract to CLP. Thus the intestine is not only a source of bacteremia but also an important target of bacterial products with major functional consequences to intestinal motility and the generation of cytokines, which participate in the development of multiple organ failure.
Asunto(s)
Ileus/etiología , Sepsis/complicaciones , Animales , Ciego/fisiología , Citocinas/biosíntesis , Cartilla de ADN , Motilidad Gastrointestinal/fisiología , Tránsito Gastrointestinal/fisiología , Ileus/microbiología , Ileus/fisiopatología , Inmunohistoquímica , Intestino Grueso/microbiología , Intestino Grueso/fisiopatología , Intestino Delgado/microbiología , Intestino Delgado/fisiopatología , Laparotomía , Masculino , Músculo Liso/patología , Músculo Liso/fisiología , Neutrófilos/fisiología , Óxido Nítrico Sintasa/biosíntesis , Óxido Nítrico Sintasa de Tipo II , Peroxidasa/metabolismo , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sepsis/microbiologíaRESUMEN
Strongyloides stercoralis is present worldwide and can cause hyperinfection in patients on long-term immunosuppressive doses of steroids, as is sometimes the case for patients treated for leprosy reactions. Strongyloides hyperinfection can present with ileus, as is discussed in this case report. Physicians, including surgeons, should be aware of this entity in order to avoid an unnecessary laparotomy. Though patients may survive if diagnosed at an early stage, strongyloides hyperinfection syndrome has a mortality rate of 87% and prevention is therefore of utmost importance.