Effects of probiotics on gastrointestinal complications and nutritional status of postoperative patients with esophageal cancer: A protocol of randomized controlled trial.

BACKGROUND: Gastrointestinal complications and malnutrition are common problems that affect postoperative rehabilitation and survival of patients with esophageal cancer. Evidence has shown that probiotics have a positive effect on improving gastrointestinal complications and nutritional status of patients with esophageal cancer after surgery, but there is a lack of prospective studies on this topic. We designed this prospective randomized controlled trial to evaluate the effects of probiotics on gastrointestinal complications and nutritional status in patients with postoperative esophageal cancer. METHODS: This is a prospective, randomized, double-blind, placebo-controlled trial. It was approved by the Clinical Research Ethics Committee of our hospital. 192 patients will be randomly divided into probiotics group and the placebo group in a 1:1 ratio. After operation, probiotics and placebo will be given orally for 8 weeks. The indexes of nutritional status and incidence of digestive tract complications will be recorded and the data will be analyzed by SPSS 18.0 software. DISCUSSION: This study will evaluate the effect of probiotics on gastrointestinal complications and nutritional status of postoperative patients with esophageal cancer. The results of this study will provide clinical basis for the use of probiotics in postoperative treatment of esophageal cancer. TRIAL REGISTRATION: OSF Registration number: D DOI 10.17605/OSF.IO/QHW86.

Disentangling Microbial Mediators of Malnutrition: Modeling Environmental Enteric Dysfunction.

Environmental enteric dysfunction (EED) (also referred to as environmental enteropathy) is a subclinical chronic intestinal disorder that is an emerging contributor to early childhood malnutrition. EED is common in resource-limited settings, and is postulated to consist of small intestinal injury, dysfunctional nutrient absorption, and chronic inflammation that results in impaired early child growth attainment. Although there is emerging interest in the hypothetical potential for chemical toxins in the environmental exposome to contribute to EED, the propensity of published data, and hence the focus of this review, implicates a critical role of environmental microbes. Early childhood malnutrition and EED are most prevalent in resource-limited settings where food is limited, and inadequate access to clean water and sanitation results in frequent gastrointestinal pathogen exposures. Even as overt diarrhea rates in these settings decline, silent enteric infections and faltering growth persist. Furthermore, beyond restricted physical growth, EED and/or enteric pathogens also associate with impaired oral vaccine responses, impaired cognitive development, and may even accelerate metabolic syndrome and its cardiovascular consequences. As these potentially costly long-term consequences of early childhood enteric infections increasingly are appreciated, novel therapeutic strategies that reverse damage resulting from nutritional deficiencies and microbial insults in the developing small intestine are needed. Given the inherent limitations in investigating how specific intestinal pathogens directly injure the small intestine in children, animal models provide an affordable and controlled opportunity to elucidate causal sequelae of specific enteric infections, to differentiate consequences of defined nutrient deprivation alone from co-incident enteropathogen insults, and to correlate the resulting gut pathologies with their functional impact during vulnerable early life windows.

Compromised nutritional status in patients with end-stage liver disease: Role of gut microbiota.

BACKGROUND: Patients with end-stage liver disease (ESLD) have a compromised nutritional status because of the liver crucial role in regulating metabolic homeostasis and energy balance. DATA SOURCES: A systematic review of literature based on extensive relevant articles published from 2001 to 2017 in English in PubMed database was performed by searching keywords such as liver disease, non-alcoholic liver disease, alcoholic liver disease, malnutrition, epigenetics, gut microbiota, and probiotics. RESULTS: Liver transplantation would be one eligible therapy for ESLD patients, even if, the clinical outcome is negatively influenced by malnutrition and/or infections. The malnutrition is a condition of nutrient imbalance with a high incidence in ESLD patients. An accurate evaluation of nutritional status could be fundamental for reducing complications and prolonging the survival of ESLD patients including those undergoing liver transplantation. In addition, the interaction among nutrients, diet and genes via epigenetics has emerged as a potential target to reduce the morbidity and mortality in ESLD patients. The malnutrition induces changes in gut microbiota causing dysbiosis with a probable translocation of bacteria and/or pathogen-derived factors from the intestine to the liver. Gut microbiota contribute to the progression of chronic liver diseases as well as hepatocellular carcinoma. The administration of probiotics modulating gut microbiota could improve all chronic liver diseases. CONCLUSIONS: This review provides an update on malnutrition status linked to epigenetics and the potential benefit of some probiotics on the management of ESLD patients. In support of this view and to reveal the constant and growing interest in this field, some clinical trials are reported.

Estudio Transversal: Prevalencia de Infecciones Respiratorias Agudas y su Asociación con Desnutrición en Pacientes Menores de 5 Años Atendidos en el Centro de Salud de Cuchil, 2016 / Cross Sectional Research: Prevalence of Acute Respiratory Tract Infections and its Association with Malnutrition in Children under 5 Years Old Treated at Cuchil's Health Center, 2016

INTRODUCCIÓN: Los niños con desnutrición presentan una mayor vulnerabilidad a la adquisición de múltiples enfermedades en relación con aquellos que cuentan una nutrición adecuada. El objetivo del presente estudio fue determinar la prevalencia de infecciones respiratorias agudas y su asociación con la desnutrición en pacientes menores de 5 años. MÉTODO: Estudio observacional descriptivo de corte transversal realizado en el Centro de Salud de Cuchil, en el cantón Sigsig durante el año 2016; se incluyeron 373 niños menores a 5 años. Se tomaron los datos de peso y longitud/talla según la normativa del Ministerio de Salud Pública, y en base a la anamnesis y examen físico se estableció el diagnóstico de infección respiratoria aguda (IRA). Para el análisis se utilizó la estadística descriptiva, chi cuadrado y razón de prevalencia con un intervalo de confianza del 95 % y un valor de p: <0.05 para determinar significancia estadística. RESULTADOS: La prevalencia de IRA fue de 31.37 %, existió una mayor prevalencia en el grupo de edad menor a 12 meses (31.62 %). La prevalencia de desnutrición fue 5.90 %. La rinofaringitis fue la principal infección diagnosticada (69.23 %). La asociación entre la desnutrición como factor predisponente para la adquisición de infección respiratoria aguda fue estadísticamente significativa (x²: 27.641; RP: 2.900; IC-95 %: 2.240*3.755; p:<0.001). CONCLUSIÓN: La prevalencia de infecciones respiratorias agudas fue alta, siendo la rinofaringitis aguda la infección de mayor frecuencia. La desnutrición es un factor de riesgo para la adquisición de IRA.(au)

BACKGROUND: Children with malnutrition are more vulnerable to acquire diseases compared with those properly nourished. The aim of the study was to determine prevalence of acute respiratory infections and its association with malnutrition in patients under 5 years of age. METHODS: A cross sectional descriptive study was performed at Cuchil's health center (Ssigsig) during 2016. 373 children under 5 years were included. Weight and length/height data were registered according to regulations established by Ecuadorian Ministry of Public Health and acute respiratory infections were diagnosed after anamnesis and physical examination. Analysis required descriptive statistics, chi-square, prevalence ratio (95 % confidence interval) and a p value <0.05 to determine statistical significance. RESULTS: Prevalence of ARI reached 31.37 % and the group under 12 months of age was mainly affected (31.62 %). Prevalence of malnutrition was 5.90 %. Rhinopharyngitis was the most frequent diagnosis (69.23 %). Association between malnutrition (as a risk factor) and prevalence of ARI was statistically significant (x²: 27.641; RP: 2.900; IC-95 %: 2.240*3.755; p: <0.001). CONCLUSION: Prevalence of acute respiratory infecctions was high. Rhinopharyngitis was the most frequent diagnosis. Malnutrition may be considered as a risk factor to develop acute respiratory infections.(au)

Protein- and zinc-deficient diets modulate the murine microbiome and metabolic phenotype.

BACKGROUND: Environmental enteropathy, which is linked to undernutrition and chronic infections, affects the physical and mental growth of children in developing areas worldwide. Key to understanding how these factors combine to shape developmental outcomes is to first understand the effects of nutritional deficiencies on the mammalian system including the effect on the gut microbiota. OBJECTIVE: We dissected the nutritional components of environmental enteropathy by analyzing the specific metabolic and gut-microbiota changes that occur in weaned-mouse models of zinc or protein deficiency compared with well-nourished controls. DESIGN: With the use of a 1H nuclear magnetic resonance spectroscopy-based metabolic profiling approach with matching 16S microbiota analyses, the metabolic consequences and specific effects on the fecal microbiota of protein and zinc deficiency were probed independently in a murine model. RESULTS: We showed considerable shifts within the intestinal microbiota 14-24 d postweaning in mice that were maintained on a normal diet (including increases in Proteobacteria and striking decreases in Bacterioidetes). Although the zinc-deficient microbiota were comparable to the age-matched, well-nourished profile, the protein-restricted microbiota remained closer in composition to the weaned enterotype with retention of Bacteroidetes. Striking increases in Verrucomicrobia (predominantly Akkermansia muciniphila) were observed in both well-nourished and protein-deficient mice 14 d postweaning. We showed that protein malnutrition impaired growth and had major metabolic consequences (much more than with zinc deficiency) that included altered energy, polyamine, and purine and pyrimidine metabolism. Consistent with major changes in the gut microbiota, reductions in microbial proteolysis and increases in microbial dietary choline processing were observed. CONCLUSIONS: These findings are consistent with metabolic alterations that we previously observed in malnourished children. The results show that we can model the metabolic consequences of malnutrition in the mouse to help dissect relevant pathways involved in the effects of undernutrition and their contribution to environmental enteric dysfunction.

Environmental enteropathy.

PURPOSE OF REVIEW: Environmental enteropathy has long been recognized as an important intermediary condition leading to chronic malnutrition in children in developing countries. Interest has lately renewed in this topic because of increased focus on improving the quality of lives as opposed to just saving them. Here, we provide an overview of recent scientific literature and our perspective about this disorder. RECENT FINDINGS: Current understanding of the disorder of environmental enteropathy is based on studies conducted decades ago. Results of some new studies on histopathologic characterization of environmental enteropathy are currently awaited. Given the challenges of diagnosing environmental enteropathy using the gold standard test of intestinal biopsy, different biomarkers have been tested as proxies of environmental enteropathy and eventually, chronic malnutrition. Available data fail to point toward a single ideal biomarker, though considerable work is still ongoing. A few interventional studies have also been conducted with improvement in environmental enteropathy as outcome. SUMMARY: The basic histopathology of environmental enteropathy has been defined previously, and more advanced analysis to study the pathophysiology of this disorder is currently being carried out. Many biomarkers, which represent the different mechanisms involved in environmental enteropathy, have been tested as proxies of environmental enteropathy. Although no single biomarker fits the description of an ideal biomarker yet, a few of the more promising biomarkers are being validated in different studies. Finally, the few interventions which have been tried to treat environmental enteropathy, thus far, are summarized.

Non-viable immunobiotic Lactobacillus rhamnosus CRL1505 and its peptidoglycan improve systemic and respiratory innate immune response during recovery of immunocompromised-malnourished mice.

The effect of non-viable Lactobacillus rhamnosus CRL1505 and its cell wall and peptidoglycan on respiratory immunity in malnourished mice was studied. Weaned mice were malnourished with a protein-free diet for 21d and received BCD during 7d (BCD) or BCD with nasal non-viable L. rhamnosus CRL1505 (BCD+UV) or its cell wall (BCD+CW) or peptidoglycan (BCD+PG) supplementation during last 2d of the treatment. Malnourished mice without treatment (MNC) and well-nourished mice (WNC) were used as controls. Mice were infected nasally with Streptococcus pneumoniae after treatments. Resistance against pneumococci was reduced in MNC mice. Repletion with BCD reduced lung and blood bacterial cell counts when compared to MNC mice but the counts did not reach the levels of the WNC group. However, when malnourished mice received BCD+UV, BCD+CW or BCD+PG, pneumococci was not detected in lung or blood samples. Pneumococcal infection increased the levels of TNF-α, IL-1ß, IL-6, and IL-10 in the respiratory tract, however the values were lower in MNC than in WNC mice. BCD+UV and BCD+PG groups showed values of phagocytes, IL-1ß and IL-6 that were similar to WNC mice, while TNF-α was significantly higher in those groups when compared to WNC mice. Moreover, BCD+UV and BCD+PG treatments improved levels of respiratory IL-10, reaching values that were superior to those observed in WNC mice. The work demonstrates for the first time that non-viable probiotic bacteria or their cellular fractions could be an interesting alternative as mucosal immunomodulators, especially in immunocompromised hosts in which the use of live bacteria might be dangerous.

Role of Helicobacter pylori infection on nutrition and metabolism.

Helicobacter pylori (H. pylori) is a gram-negative pathogen that is widespread all over the world, infecting more than 50% of the world's population. It is etiologically associated with non-atrophic and atrophic gastritis, peptic ulcer and shows a deep association with primary gastric B-cell lymphoma and gastric adenocarcinoma. Recently, the medical research focused on the modification of the gastric environment induced by H. pylori infection, possibly affecting the absorption of nutrients and drugs as well as the production of hormones strongly implicated in the regulation of appetite and growth. Interestingly, the absorption of iron and vitamin B12 is impaired by H. pylori infection, while infected subjects have lower basal and fasting serum levels of ghrelin and higher concentration of leptin compared to controls. Since leptin is an anorexigenic hormone, and ghrelin stimulates powerfully the release of growth hormone in humans, H. pylori infection may finally induce growth retardation if acquired very early in the childhood and in malnourished children. This review is focused on the nutritional effects of H. pylori infection, such as the reduced bioavailability or the malabsorbption of essential nutrients, and of gastrointestinal hormones, as well as on the relationship between H. pylori and the metabolic syndrome.

Protective effect of probiotics on intestinal barrier function in malnourished rats after liver transplantation.

BACKGROUND: Most patients waiting for liver transplantation have end-stage liver diseases with malnutrition, which is prone to induce intestinal barrier dysfunction after liver transplantation. We aimed to study the effect of probiotics on intestinal barrier function in malnourished rats following liver transplantation with long-term antibiotics. METHODS: Twelve Lewis rats were selected as donors. Twelve BN rats, which served as recipients, were subjected to malnutrition by semi-starvation for 4-5 weeks. They were randomly divided into two groups: a control group which received phosphate-buffered saline and a probiotics group which received Bifidobacterium and Lactobacillus. All recipients were injected with intramuscular imipenem and subcutaneous cyclosporine A. Furthermore, six normal BN rats without any drugs or operations served as a normal group. Eight days after operation, all rats were sacrificed for examination of the following parameters: serum levels of endotoxin and TNF-alpha, bacterial translocation, intestinal microflora, ileocecal sIgA, lymphocyte numbers, and phenotypes (CD4, CD8, alphabetaTCR, gammadeltaTCR) of Peyer's patches. RESULTS: In recipients subjected to malnutrition, weight decreased by 20% and they survived until 8 days after operation. Compared with the normal group, all recipients on postoperative day 8 showed increased levels of serum endotoxin and TNF-alpha as well as increased counts of translocated bacteria. Meanwhile, there were decreases in counts of Bifidobacterium and Lactobacillus in the ileocecum, sIgA concentration, and lymphocytes of Peyer's patches. Moreover, partial alteration in lymphocyte phenotypes was evidenced by elevated ratios of CD8+ and gammadeltaTCR+ lymphocytes. In contrast, compared to the control group, supplementation with probiotics reduced the levels of serum endotoxin, TNF-alpha and bacterial translocation, increased the counts of Bifidobacterium and Lactobacillus, the concentration of sIgA and lymphocytes of Peyer's patches, and also slightly restored the alteration of lymphocyte phenotypes. CONCLUSION: Supplementation with probiotics including Bifidobac-terium and Lactobacillus promoted partial restoration of intestinal microflora and improved intestinal barrier function in malnourished rats after liver transplantation with long-term use of antibiotics.

Impact of H. pylori on growth: is the infection or mucosal disease related to growth impairment?

BACKGROUND: Helicobacter pylori (H. pylori) has been recognized as one of the most common chronic bacterial infections in the world. Most children are colonized in early childhood, and the infection will last a lifetime unless the child is treated with appropriate antibiotics. AIM: To evaluate whether H. pylori infection has an influence on growth and whether the severity of endoscopic findings relates to the growth impairment. METHODS: We formed four groups based on the presence or absence of H. pylori infection and gastrointestinal complaints as follows: group I: RAP +/H. pylori+; group II: RAP +/H. pylori-; group III: RAP -/H. pylori+; group IV: RAP -/H. pylori-. The relationship between endoscopic appearances, histological severity of gastritis, and antral H. pylori density with growth parameters was evaluated. RESULTS: The BMI standard derivation scores of groups I and II were significantly lower than those of asymptomatic controls independent of their H. pylori status. A significant difference in height for age standard derivation scores was observed only between groups I and IV. When we compared the BMI and height for age standard derivation scores of group III and group IV combined with that of the endoscopically normal children in the recurrent abdominal pain group, there was no significant difference between the two groups. CONCLUSION: Recurrent abdominal pain associated with gastric mucosal injury plays a role in a decrease in BMI independent of H. pylori infection. However, if recurrent abdominal pain originates from H. pylori infection, it appears that linear growth is also affected.