Mechanism of gut-microbiota-liver axis in the pathogenesis of intestinal failure-associated liver disease / 中华胃肠外科杂志

Intestinal failure (IF) is defined as the critical reduction of functional intestines below the minimum needed to absorb nutrients and fluids, so that intravenous supplementation with parenteral nutrition (PN) is required to maintain health and/or growth. Although the benefits are evident, patients receiving PN can suffer from serious cholestasis due to lack of enteral feeding and small intestinal bacterial overgrowth (SIBO). One such complication that may arise is intestinal failure-associated liver disease (IFALD). Evidences from recent studies suggest that alterations in the intestinal microbiota, as well as intraluminal bile acid driven signaling, may play a critical role in both hepatic and intestinal injury. Since Marshall first proposed the concept of the gut-liver axis in 1998, the role of gut-liver axis disorders in the development of IFALD has received considerable attention. The conversation between gut and liver is the key to maintain liver metabolism and intestinal homeostasis, which influences each other and is reciprocal causation. However, as a "forgotten organ" , intestinal microbiota on the pathogenesis of IFALD has not been well reflected. As such, we propose, for the first time, the concept of gut-microbiota-liver axis to emphasize the importance of intestinal microbiota in the interaction of gut-liver axis. Analysis and research on gut-microbiota-liver axis will be of great significance for understanding the pathogenesis of IFALD and improving the prevention and treatment measures.

Environmental enteric dysfunction and growth / Disfunção entérica ambiental e crescimento

Abstract Objective: To describe the current indicators of environmental enteric dysfunction and its association with linear growth deficit and the height-for-age anthropometric indicator. Data sources: Narrative review with articles identified in PubMed and Scopus databases using combinations of the following words: environmental, enteric, dysfunction, enteropathy, and growth, as well as the authors' personal records. Data synthesis: In the last 15 years, new non-invasive markers have been investigated to characterize environmental enteric dysfunction; however, the best tests to be used have not yet been identified. There is evidence that, in environmental enteric dysfunction, a systemic inflammatory process may also occur as a consequence of increased intestinal permeability, in addition to intestinal mucosa abnormalities. Bacterial overgrowth in the small intestine and changes in fecal microbiota profile have also been identified. There is evidence indicating that environmental enteric dysfunction can impair not only full growth but also the neuropsychomotor development and response to orally administered vaccines. It is important to emphasize that the environmental enteric dysfunction is not a justification for not carrying out vaccination, which must follow the regular schedule. Another aspect to emphasize is the greater risk for those children who had height impairment in early childhood, possibly associated with environmental enteric dysfunction, to present overweight and obesity in adulthood when exposed to a high calorie diet, which has been called "triple burden." Conclusions: According to the analyzed evidence, the control of environmental enteric dysfunction is very important for the full expression of growth, development, and vaccine response in the pediatric age group.

Resumo Objetivo: Descrever os indicadores atuais da disfunção entérica ambiental e sua relação com déficit de crescimento linear e com o indicador antropométrico estatura-idade. Fontes dos dados: Revisão narrativa com artigos identificados no PubMed e Scopus com o uso de combinações das seguintes palavras: environmental, enteric, dysfunction, enteropathy e growth e dos arquivos pessoais dos autores. Síntese dos dados: Nos últimos 15 anos, vem sendo pesquisados novos marcadores não invasivos para caracterizar disfunção entérica ambiental. No entanto, ainda não foram identificados os melhores testes a serem usados. Existem evidências de que na disfunção entérica ambiental, além das anormalidades da mucosa intestinal, pode ocorrer também processo inflamatório sistêmico em consequência da maior permeabilidade intestinal. Sobrecrescimento bacteriano no intestino delgado e mudança no perfil da microbiota fecal também estão sendo identificados. Evidências indicam que a disfunção entérica ambiental pode comprometer não somente o pleno crescimento como também comprometer o desenvolvimento neuropsicomotor e a resposta de vacinas administradas por via oral. É importante destacar que a disfunção entérica ambiental não é justificativa para não fazer a vacinação, que deve seguir o calendário normal. Um outro aspecto a ser ressaltado é o risco maior dessas crianças que tiveram comprometimento da estatura na infância precoce, possivelmente associado à disfunção entérica ambiental, apresentarem na idade adulta excesso de peso e obesidade quando expostas a uma dieta rica em calorias, o que tem sido chamado "triple burden". Conclusões: De acordo com as evidências analisadas, o controle da disfunção entérica ambiental é muito importante para plena expressão do crescimento, desenvolvimento e resposta vacinal na faixa etária pediátrica.

Cecopexia como tratamiento del estreñimiento crónico / Cecopexy as treatment for chronic constipation

Determinar cuales son los principales síntomas de los pacientes con estreñimiento crónico debido a ciego movil y los resultados postoperatorios al someterse a cecopexia. Estudio descriptivo, prospectivo y transversal donde se incluyeron todos los pacientes con diagnóstico de estreñimiento crónico de tránsito lento (ciego móvil) que acudieron a la Unidad de Coloproctología del Hospital Universitario de Caracas, desde marzo 2007 a marzo 2010, y a quienes se le realizó un interrogatorio (criterios de Roma III, escala de Wexner), examen físico y estudios de protocolo para estreñimiento (tiempo de transito) colónico, eco y/o videodelecografía, cecografía y colonoscopia de ser justificada) para luego ser sometidos a cecopexia. Se incluyeron 52 pacientes, 50 pacientes (96%) mujeres y 2 (4%) hombres en edades comprendidas entre 19 y 62 años. Se aperaron 22 pacientes (44%), a quienes se les evaluó los principales motivos de consulta tales como disminución de la frecuemcia evacuatoria presente en el 100% de los casos, dolor abdominal y heces duras (96%). defecación obstruida (87%), uso excesivo de laxantes (74%), distensión abdominal (65%) y meteorismo (52%) entre otros. Las patologías asociadas más frecuentes fueron hemorroides en 38% de los casos e intususcepción y rectocele en 30%. El tiempo de tránsito colónico preoperatorio fue anormal en todos los casos, ubicándose los marcadores tanto en colon derecho como izquierdo en 57% y 43% sólo en colon derecho el tiempo de tránsito colónico postoperatorio fue normal en el 83% de los casos y en 17% alterado, 9% en colon izquierdo, 4% derecho y 4% ambos. La cecografía preoperatoria fue grado III en 70% de los casos, grado II 26% y grado I 4% modificandose en el postoperatorio 52% normales, 26% grado I, 18% grado II y 4% grado III. De los 22 pacientes operados, 12(57%) se les realizó como procedimiento asociado a la cecopexia una cura de rectocele vía transanal. La escala de Wexner preoperatoria fue de 6 como promedio...

To determine which are the main symptoms of patients with chronic constipation due to mobile cecum and postoperative outcomes to undergo cecopexy. A descriptive atudy, transverse and prospective, where we included all patients with a diagnosis of chronic constipation of slow traffic (mobile cecum) who came to the Coloproctology Unit of Hospital Universitario de Caracas, from March 2007 to March 2010, and who was conducted an interrogation (Roma III, Wexner scale critería), physical examination and studies of protocol for constipation (colonic transit time, ultrasound and/or videodelecography and colonoscopy to be justified) to then be submitted to cecopexy. We included 52 patients, 50 (96%) women and 2 (4%) men aged between 19 and 62 years. Operated 22 patients (44%) who was assessed the main reasons for consulting such as reduction of the evacuatory frequency present in 100% of the cases, abdominal pain and hard stools (96%), obstructed defecation (87%), over use of laxatives (74%), abdominal distention (65%) and meteorism (52%) among others. The most frequent associated diseases were hemorrhoids in 38% of cases and intussusception and rectocele by 30%. Preoperative colonic transit time was abnormal in all cases, placing markers both in right colon as left by 57% and 43% only in right colon postoperative colonic transit time was normal in 83% of cases and 17% altered, 9% in left colon, 4% right, and 4% both, The preoperative cecography was I grade III in 70% of cases, grade II 26% grade I 4%, modifying in postoperative normal 52%, 26% grade I, 18 per cent grade II and 4% grade III. Of 22 operated patients, 12 (57%) was them performed as associated with the cecopexy procedure a rectocele transanal repair. The scale of Wexner was 6 average and 16 postoperative, like the evacuatory frequency which improved on a daily basis by 69 per cent of cases, more than I time a week at 22% and 9% without improvement. The most frequent complications were mild in 48%...

Curso de Reumatologia: aula 5: anti-inflamatórios não hormonais e alterações intestinais / Course of Rheumatology: class 5: nonsteroidal anti-inflammatory drugs and intestinal alterations

A enteropatia relacionada aos anti-inflamatórios não hormonais (ou não esteroides) é um processo gradual que envolve efeito tóxico direto à mucosa, lesão mitocondrial, quebra da integridade intercelular, recirculação êntero-hepática do anti-inflamatório e ativação neutrofílica pelo conteúdo intraluminal, inclusive por bactérias. A mediação pela cicloxigenase provavelmente é menos importante do que no trato gastrointestinal superior. Estudos com a nova modalidade endoscópica, como a que se utiliza de cápsula endoscópica, demonstram anormalidades relacionadas aos anti-inflamatórios não esteroides (AINEs), que incluem inflamação, erosões, fibrose, estenoses, lesões enantemáticas, erosões patequiais, perfurações e formação de membranas diafragmáticas no jejuno, íleo e colon.

Nonsteroidal anti-inflammatory drug enteropathy is a stepwise process involving direct mucosal toxity, mitochondrial damage, breakdown of intercellular integrity enterohepatic recirculation and neutrophil activation by liminal contents including bacteria. Unlike upper gastrointestinal toxity, cyclooxygenase-mediated mechanisms are probably less important. Newer imaging modalities such as capsule endoscopy studies demonstrate nonsteroidal anti-inflammatory drug-induced abonormalities that include inflammation, erosion, fibrosis, stricture, red spots, petechiae erosions, perforation, and formation of mucosal diaphragms in the jejunum, ileum and colon.

Diferença de patogenicidade entre Escherichia coli enteroinvasora e Shigella flexneri em modelo experimental de infecção intestinal / Diference in pathogenicity between enteroinvasive Escherichia coli and Shigella flexneri in an experimental model of intestinal infection

Neste trabalho, esclarecemos tópicos da patogenicidade de EIEC que sustentam a sua menor virulência quando comparada à S. flexneri, e mostramos a importância das células dendríticas (CD) nesse processo. Estudou-se o comportamento de EIEC e S. flexneri quando em contato com células Caco-2, avaliando-se uma cinética de expressão dos genes envolvidos na invasão e disseminação bacteriana. Em geral, todos os genes foram menos expressos em EIEC, fato corroborado pelo fenótipo de disseminação bacteriana, onde EIEC foi menos eficiente do que Shigella. Também foi avaliada a modulação da resposta inflamatória de células dendríticas intestinais murinas pela produção de citocinas, expressão de moléculas co-estimulatórias e apresentação de antígenos, após desafio das células com as bactérias. Os resultados sugerem que EIEC induz a uma resposta protetora ao hospedeiro, enquanto que Shigella estaria "driblando" o sistema imune, além de provavelmente super-estimular o sistema imune adaptativo, fato que poderia levar a um agravamento da doença. As ações integradas das células Caco-2, células dendríticas e estímulos bacterianos foram estudadas em cocultura celular. Observou-se que EIEC e suas proteínas secretadas induzem a migração das CDs ao compartimento apical da co-cultura; nada foi observado quando o desafio se deu com Shigella...

¿Existe en la constipación idiopática severa un trastorno difuso de la motilidad intestinal? / Disturbances of small intestinal motility in patients with chronic constipation

Background: Studies in patients with chronic severe constipation, suggest the presence of a diffuse motor disorder of the gastrointestinal tract. Aim: To investigate small bowel motor activity in a group of patients with severe constipation. Material and Methods: Forty three patients (age range 13 to 70 years, 40 women) with severe constipation referred to our motility laboratory, where studied. Ten had a previous colectomy. Radiological examinations showed a megacolon in 30 and dilatation of small intestinal loops in nine; the remaining X rays studies were normal. Small intestinal motility was studied using perfused catheters and external transducers. Results: Ten patients had normal motor recordings. Eight patients showed a neuropathic disorder characterized by a continuous irregular pattern of contractions of normal amplitude, with absence of phase III of the migrating motor complex (MMC). Sixteen presented a normal MMC associated to a decreased amplitude of contractions (Miopatic disorder). Nine showed both types of motor disorders (Mixed pattern). Normal radiological findings were more commonly associated to normal manometric recordings. By contrast, an altered motor activity, mainly of myopathic and mixed type motor disorder, was observed in all patients with dilated small intestinal and colonic loops. Conclusions: The presence of small intestinal motor disorders was a frequent finding in this selected group of patients with chronic constipation.

Epithelial effects of proteinase-activated receptors in the gastrointestinal tract

The intestinal epithelium plays a crucial role in providing a barrier between the external environment and the internal milieu of the body. A compromised mucosal barrier is characteristic of mucosal inflammation and is a key determinant of the development of intestinal diseases such as Crohn's disease and ulcerative colitis. The intestinal epithelium is regularly exposed to serine proteinases and this exposure is enhanced in numerous disease states. Thus, it is important to understand how proteinase-activated receptors (PARs), which are activated by serine proteinases, can affect intestinal epithelial function. This review surveys the data which demonstrate the wide distribution of PARs, particularly PAR-1 and PAR-2, in the gastrointestinal tract and accessory organs, focusing on the epithelium and those cells which communicate with the epithelium to affect its function. PARs have a role in regulating secretion by epithelia of the salivary glands, stomach, pancreas and intestine. In addition, PARs located on subepithelial nerves, fibroblasts and mast cells have important implications for epithelial function. Recent data outline the importance of the cellular site of PAR expression, as PARs expressed on epithelia may have effects that are countered by PARs expressed on other cell types. Finally, PARs and their ability to promote epithelial cell proliferation are discussed in terms of colon cancer.

Triplicación de íleon proximal con duplicación esofágica / Triplication of the proximal ileon and esophageal duplication

Las duplicaciones intestinales son anomalías infrecuentes; el sitio de presentación más común es el ileon terminal. Se presenta el caso de un niño con malformación doble de ileon terminal (triplicación) con porción tubular y quística simultánea a una duplicación esofágica. Esta anomalía probablemente no ha sido descrita; y debe ser excepcional. El cuadro se inició con dolor abdominal, sangrado del tubo digestivo y posteriormente abdomen agudo. El diagnóstico se estableció mediante gammagrafía con Tecnecio 99 en el caso de la lesión intestinal; con radiografía de tórax, esofagograma y tomografía axial por computadora de la lesión torácica. Se trataron quirúrgicamente ambas anomalías; la torácica por toracotomía derecha; las lesiones intestinales con laparotomía exploradora y resección del ileon terminal en las partes afectadas

Alteraçöes da permeabilidade intestinal em crianças / Alterations of the intestinal permeability in children

É apresentada uma revisäo atualizada sobre permeabilidade intestinal, enfocando as vias de permeabilidade, as substâncias-testes e as técnicas mais comumente empregadas para estudo e quantificaçäo da mesma. Säo também destacadas algumas afecçöes pediátricas associadas com anormalidade da permeabilidade intestinal

Intestinal amebiasis: histopathologic features in experimentally infected mice

Intestinal amebiasis is still an important health problem in developing regions of the world. In order to advance our knowledge on the pathogenesis and to test the relevance of recently obtained in vitro observations, suitable in vivo experimental models of intestinal amebiasis are needed. In the past a variety of laboratory animals have been used, but the mouse, whose genetic and immunology is well known, has been seldomly used. Therefore, Entamoeba histolytica strain HM1:IMSS was directly inoculated into the cecum of C3H/HeJH mice, which were sacrified at 5, 10, 15, 20, 25 and 30 days for histopathologic analysis. An ulcerative inflammatory disease highly reminiscent of human amebiasis was observed. Early 5 day lesions consited of tiny erosions of the surface epithelium which evolved to deeper and more extensive destructive lesions of the cecal wall. Indeed, flask-shaped ulcers, intestinal perforations and intramural abscess formation were observed at later time. It was noticeable that, depite the lack of obvious significant tissue invasion by amebae, ulcerative disease was extensive and found virtually in all mice. These observations support the view that tissue invasion by trophozoites is not necessarily required for ulcerative disease to occur, suggesting a role for toxic factors released by amebae

Symptomatic environmental enteropathy in infancy: bacterial proliferation, funcional and morphological alterations of the small bowel

Asymptomatic Environmental enteropathy may occur in the low social economic stratum of the population temporarily, thus contributing to marginal malnutrition. Bacterial proliferation in the upper portions of the small bowel may be responsible for alterations in the digestive-absorptive function leading to nutritional dwarfism. Forty infants of the Cidade Leonor slum who were under one year of age and presented with asymptomatic environmental enteropathy were investigated for digestive-absorptive function, bacterial proliferation in the small bowel lumen, and jejunal morphology. The mean value of the D-xylose absorption test was 21.0 ñ 10.0 mg per cent, significantly lower than controls (48.0 ñ 13.8 mg per cent) (p < 0.001). Bacterial proliferation in the small bowel of the colonic type was identified in 25 (62,5 per cent) of the infants and jejunal mucosa abnormalities were found in 29(72.5 per cent) of the specimens. Grade II villous atrophy was the most frequent alteration found. The inflammatory infiltration in the lamina propria increased in the total group, varying from light to severe. Alterations in the microecology of the small intestine can occur even in the absence of diarrhea. Therefore, the nonexistence of symptoms does not necessarily imply a condition of weillbeing. If true measures are proposed to improve the quality of life in these poor communities the whole infant population must be taken into account and not only the group with overt symptoms