El climaterio como etapa fisiológica crucial en la prevención de la enfermedad cardiovascular / The climacteric as a crucial physiological stage in the prevention of cardiovascular disease

El climaterio es una etapa fisiológica que permite al médico reconocer tempranamente los riesgos de patologías y la gran oportunidad de revertirlas. Este trabajo examinará la evidencia actual de la terapia hormonal en la prevención primaria de la enfermedad cardiovascular en mujeres, así como la importancia que igualmente tienen la indemnidad de los ovarios, el peso normal, el uso correcto de antibióticos, la preservación de la microbiota intestinal, las dietas antioxidantes, los estilos de vida saludables y el obligatorio abandono del hábito de fumar.

Gut microbiota and the use of probiotics in constipation in children and adolescents: systematic review / Microbiota intestinal e emprego dos probióticos na constipação intestinal em crianças e adolescentes: revisão sistemática

ABSTRACT Objective: To perform a systematic review of literature data on gut microbiota and the efficacy of probiotics for the treatment of constipation in children and adolescents. Data source: The research was performed in the PubMed, the Scientific Electronic Library Online (SciELO) and the Latin American and Caribbean Health Sciences Literature (LILACS) databases in English, Portuguese and Spanish. All original articles that mentioned the evaluation of the gut microbiota or the use of probiotics in children with constipation in their title and abstract were selected. Data synthesis: 559 articles were found, 47 of which were selected for reading. From these, 12 articles were included; they studied children and adolescents divided into two categories: a gut microbiota evaluation (n=4) and an evaluation of the use of probiotics in constipation therapy (n=8). The four papers that analyzed fecal microbiota used different laboratory methodologies. No typical pattern of gut microbiota was found. Regarding treatment, eight clinical trials with heterogeneous methodologies were found. Fifteen strains of probiotics were evaluated and only one was analyzed in more than one article. Irregular beneficial effects of probiotics have been demonstrated in some manifestations of constipation (bowel frequency or consistency of stool or abdominal pain or pain during a bowel movement or flatulence). In one clinical trial, a complete control of constipation without the use of laxatives was obtained. Conclusions: There is no specific pattern of fecal microbiota abnormalities in constipation. Despite the probiotics' positive effects on certain characteristics of the intestinal habitat, there is still no evidence to recommend it in the treatment of constipation in pediatrics.

RESUMO Objetivo: Realizar revisão sistemática dos dados da literatura sobre a microbiota intestinal e a eficácia dos probióticos para o tratamento da constipação intestinal em crianças e adolescentes. Fonte de dados: Foi realizada busca nas bases de dados PubMed, Scientific Electronic Library Online (SciELO) e Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), em inglês, português e espanhol. Foram selecionados, pelo título e pelo resumo, todos os artigos originais que avaliaram a microbiota intestinal ou o emprego de probióticos em crianças com constipação intestinal. Síntese dos dados: Foram encontrados 559 artigos, dos quais 47 foram selecionados para leitura. Destes, foram incluídos 12 artigos que estudaram crianças e adolescentes distribuídos em duas categorias: avaliação da microbiota intestinal (n=4) e avaliação do emprego dos probióticos na terapêutica da constipação intestinal (n=8). Os quatro artigos que analisaram a microbiota fecal utilizaram metodologias laboratoriais diferentes. Não foi observado um padrão típico de microbiota intestinal. Quanto ao tratamento, foram encontrados oito ensaios clínicos com metodologias heterogêneas. Foram avaliadas 15 cepas de probióticos e apenas uma foi avaliada em mais de um artigo. Foram evidenciados efeitos benéficos não uniformes dos probióticos em algumas manifestações da constipação intestinal (frequência evacuatória, consistência das fezes, dor abdominal, dor ao evacuar ou flatulência). Em apenas um ensaio clínico foi obtido completo controle da constipação intestinal sem o emprego concomitante de laxantes. Conclusões: Não existe um padrão específico de anormalidades da microbiota fecal na constipação intestinal. Apesar dos efeitos positivos dos probióticos em determinadas características do hábito intestinal, ainda não existem evidências que permitam sua recomendação no tratamento da constipação intestinal em pediatria.

Effect of Gegen Qinlian Decoction and it's different compatibility groups on gut microbiota in rats with acute enteritis based on high-throughput sequencing / 中国中药杂志

This study was designed to investigate the effect of Gegen Qinlian(GGQL) Decoction and its different compatibility groups on gut microbiota in rats with acute enteritis, and to explore the efficacy of GGQL Decoction in improving acute enteritis and gut microbiota. Male SD rats were randomly divided into control group, model group, positive control group(SASP), GGQL decoction group, Glycyrrhizae-free group(QGC), Puerariae-free group(QGG), Qinlian-free group(QQL), and Qinlian group(QL). The pathological sections and detection indexes of the rats were observed before and after modeling and administration. After 7 days of administration, fecal samples from 24 rats were collected and Illumina Miseq platform was used for high-throughput sequencing. From the anti-inflammatory and pharmacodynamic indicators, the effect was the most obvious in GGQL Decoction group, QGC group, QGG group and QL group(P<0.05). The alpha diversity and beta diversity showed that there were significant differences in the composition of intestinal flora in each group. As compared with the model group, the increased abundance and diversity of the flora caused by acute inflammation could be down-regulated in all groups except QQL group(P<0.05). The differential bacteria were explored by using LEfSe analysis, and the results showed that Bifidobacterium and other beneficial bacteria only appeared in the normal group. As compared with the normal group, Lactobacillus was significantly reduced(P<0.01), and Bacteroides, Flavonifractor and Clostridium_sensu_stricto_1 were up-regulated in model group(P<0.05, P<0.01). As compared with the model group, the number of Akkermansia was significantly increased(P<0.05), and the number of Clostridium_sensu_stricto_1 associated with intestinal inflammatory diseases was decreased in the GGQL Decoction group, QGC group and QL group. QGC group and QQL group caused the up-regulation of Ruminococcaceae and induced enrichment of Desulfovibrio which could lead to colon cell toxicity; QGG group caused the up-regulation of Proteobacteria and Burkhonderiales. The study suggests that the GGQL Decoction may play a role in the treatment of acute enteritis partially through improving the intestinal barrier, regulating the immune response and the structure of gut microbiota.

Preliminary study of Realgar and arsenic trioxide on gut microbiota of mice / 中国中药杂志

The aim of this paper was to observe the effect of Realgar and arsenic trioxide on gut microbiota. The mice were divided into low-dose Realgar group(RL), medium-dose Realgar group(RM), high-dose Realgar group(RH), and arsenic trioxide group(ATO), in which ATO and RL groups had the same trivalent arsenic content. Realgar and arsenic trioxide toxicity models were established after intragastric administration for 1 week, and mice feces were collected 1 h after intragastric administration on day 8. The effects of Realgar on gut microbiota of mice were observed through bacterial 16 S rRNA gene sequences. The results showed that Lactobacillus was decreased in all groups, while Ruminococcus and Adlercreutzia were increased. The RL group and ATO group were consistent in the genera of Prevotella, Ruminococcus, and Adlercreutzia but different in the genera of Lactobacillus and Bacteroides. Therefore, the effects of Realgar and arsenic trioxide with the same amount of trivalent arsenic on gut microbiota were similar, but differences were still present. Protective bacteria such as Lactobacillus were reduced after Realgar administration, causing inflammation. At low doses, the number of anti-inflammatory bacteria, such as Ruminococcus, Adlercreutzia and Parabacteroides increased, which can offset the slight inflammation caused by the imbalance of bacterial flora. At high doses, the flora was disturbed and the number of Proteobacteria was increased, with aggravated intestinal inflammation, causing edema and other inflammatory reactions. Based on this, authors believe that the gastrointestinal reactions after clinical use of Realgar may be related to flora disorder. Realgar should be used at a small dose in combination with other drugs to reduce intestinal inflammation.

Oral Administration of Citrus Extracts in Suckling Piglets

Abstract An experiment was conducted to evaluate the performance of suckling piglets subjected to oral administration of citrus extracts (CE). Twenty sows were used with ten sucking piglets on average initial weight of 1.26 kg (± 0.32) for 21 days. The experimental design was a randomized complete block design with two treatments: Negative Control (without antimicrobials) and Citrus Extracts (ascorbic acid + flavonoids, oral administration of 0.3 mg kg of BW via pigdoser) with ten repetitions each. The number of live-born piglets in females PO5 was 21% higher than in PO3 sows. Sows where piglets received CE showed a 10% higher (P <0.05) feed intake in the last week of lactation. From 8 to 21 days, the feed conversion of NC sows was 23 and 38% lower (P <0.05) than sows where piglets received CE. Piglet mortality was 13.4% in NC group and 3.9% in CE group in a single dose on the third day of life. The villous length in the duodenum was 24% higher (P <0.01) in piglets receiving CE. The administration of CE increased 19% (P = 0.02) the villous length of the ileum region of suckling piglets. Frequency of normal feces was higher (P<0.05) in piglets CE group. Oral administration of CE containing flavonoids and ascorbic acid to suckling piglets not improves the piglet growth. However, it alters the gut morphology, and reduces the frequency of diarrhea during suckling period. Parity order interferes on feed intake, feed conversion of sows and performance of litters.

Linderae radix ethanol extract attenuates alcoholic liver injury via attenuating inflammation and regulating gut microbiota in rats

This study aimed to explore the influence of gut microbiota alterations induced by Linderae radix ethanol extract (LREE) on alcoholic liver disease (ALD) in rats and to study the anti-inflammatory effect of LREE on ALD through the lipopolysaccharide (LPS) toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway. ALD rat models were established by intragastric liquor [50% (v/v) ethanol] administration at 10 mL/kg body weight for 20 days. Rats were divided into six groups: normal group (no treatment), model group (ALD rats), Essentiale group (ALD rats fed with Essentiale, 137 mg/kg), and LREE high/moderate/low dose groups (ALD rats fed with 4, 2, or 1 g LREE/kg). NF-κB and LPS levels were evaluated. Liver pathological changes and intestinal ultrastructure were examined by hematoxylin and eosin staining and transmission electron microscopy. The gut microbiota composition was evaluated by 16S rDNA sequencing. Expression levels of TLR4 and CD68 in liver tissue, and occludin and claudin-1 in intestinal tissue were measured. LREE treatment significantly reduced NF-κB and LPS levels, improved liver pathological changes, and ameliorated intestinal ultrastructure injury. Meanwhile, LREE-fed groups showed a higher abundance of Firmicutes and a lower abundance of Bacteroidetes than the rats in the model group. Administration of LREE suppressed TLR4 overexpression and promoted the expression of occludin and claudin-1 in intestine tissue. Thus, LREE could partly ameliorate microflora dysbiosis, suppress the inflammatory response, and attenuate liver injury in ALD rats. The protective effect of LREE might be related to the LPS-TLR4-NF-κB pathway.

Segurança e Benefício do Uso de Probióticos em Pacientes Submetidos ao TCTH: Revisão Integrativa / Safety and Benefit of Using Probiotics in Patients Undergoing HSCT: Integrative Review / Seguridad y Beneficio del Uso de Probióticos en Pacientes Sometidos al TCTH: Revisión Integradora

Introdução: O transplante de células-tronco hematopoiéticas (TCTH) é um dos potenciais tratamentos curativos utilizados para pacientes com doenças hematológicas e outras doenças imunes. Durante o transplante, o paciente é submetido ao condicionamento e a outros tratamentos, como radioterapia e quimioterapia, o que pode causar a perda da diversidade da microbiota intestinal. A manipulação da microbiota intestinal com probióticos vem sendo apontada como uma estratégia de prevenção de complicações nos pacientes submetidos ao TCTH. Objetivo: Identificar se há evidências científicas relacionadas à segurança e aos benefícios da utilização de probióticos em pacientes submetidos ao TCTH. Método: Revisão integrativa com base em estudos que abordassem o uso de probióticos para o caso específico de pacientes submetidos ao TCTH publicados entre 2000 a 2018. Resultados: Foram selecionados cinco estudos que atenderam aos critérios de inclusão e exclusão, com um total de 52 pacientes. A utilização de probióticos na prevenção e/ou tratamento da diarreia tem mostrado resultados positivos em pacientes com diarreia induzida por antibióticos ou por infecções bacterianas, porém os estudos ainda não destacam benefícios no uso de probióticos no caso específico de pacientes submetidos ao TCTH. Poucos estudos mostram o uso de probióticos para auxílio na melhora dos sintomas associados a infecções ou bacteremias em pacientes imunossuprimidos. Conclusão: O uso de probióticos na população submetida ao TCTH e em imunossuprimidos ainda é controverso, sendo necessários mais estudos que demonstrem os benefícios no uso dessa estratégia para esse público.

Introduction: Hematopoietic stem cell transplantation (HSCT) is one of the potential curative treatments used for patients with hematological and other immune diseases. During transplantation, the patient undergoes conditioning and other treatments, such as radiotherapy and chemotherapy, which may cause loss of the intestinal microbiota diversity. The manipulation of the intestinal microbiota with probiotics has been pointed out as a strategy to prevent complications in patients undergoing HSCT. Objective: To identify if there is scientific evidence related to the safety and benefits of the use of probiotics in patients submitted to HSCT. Method: Integrative review based on studies addressing the use of probiotics for the specific case of patients undergoing HSCT published between 2000 and 2018. Results: Five studies that met the inclusion and exclusion criteria were eligible, with a total of 52 patients. The use of probiotics in the prevention and/or treatment of diarrhea has shown positive results in patients with antibiotic-induced diarrhea or bacterial infections, but the studies do not yet emphasize the benefits of using probiotics in the specific case of patients submitted to HSCT. Few studies show the use of probiotics to help the improvement of the symptoms associated to infections or bacteremia in immunosuppressed patients. Conclusion: The use of probiotics in the population submitted to HSCT and immunosuppressed is still controversial, and further studies are necessary to demonstrate the benefits of using probiotics for this public.

Introducción: El trasplante de células madre de las hematopoyéticas (TCTH) es uno de los posibles tratamientos curativos utilizados para pacientes con enfermedades hematológicas y otras enfermedades inmunes. Durante el transplante, el paciente es sometido al condicionamiento ya otros tratamientos, como radioterapia y quimioterapia, lo que puede causar la pérdida de la diversidad de la microbiota intestinal. La manipulación de la microbiota intestinal con probióticos viene siendo apuntada como una estrategia de prevención de complicaciones en los pacientes sometidos al TCTH. Objetivo: Identificar si hay evidencias científicas relacionadas con la seguridad y beneficios de la utilización de probióticos en pacientes sometidos al TCTH. Método: Revisión integradora basada em estúdios que abordan el uso de probióticos para el caso específico de pacientes sometidos a TCMH publicados entre 2000 y 2018. Resultados: Fueron elegibles 4 estudios que atendieron a los criterios de inclusión y exclusión, con un total de 52 pacientes. La utilización de probióticos en la prevención y/o tratamiento de la diarrea ha mostrado resultados positivos en pacientes con diarrea inducida por antibióticos o por infecciones bacterianas, pero los estudios aún no aportan beneficios en el uso de probióticos en pacientes sometidos al TCTH. Pocos estudios muestran infecciones o bacterias en pacientes inmunosuprimidos que utilizaron probióticos para ayudar en la mejora de los síntomas asociados al tratamiento. Conclusión: El uso de probióticos en la población sometida al TCTH e inmunosuprimidos aún es controvertido, siendo necesarios más estudios que comprueben los beneficios en el uso de probióticos para este público.

Dietas altas en grasas y sus efectos sobre el intestino / Diets high in fats and their effects on the intestine

El objetivo de esta revisión fue exponer el conocimiento actual sobre la relación existente entre dietas altas en grasa (DAG), alteraciones morfológicas de la mucosa intestinal, efectos inflamatorios y cáncer intestinal. Las DAG inicialmente producen aumento de la microbiota patógena, lo que reduce la cantidad y calidad de la secreción de los exocrinocitos caliciformes, disminuyendo la efectividad de la barrera intestinal. Las bacterias y sus lipopolisacaridos (LPS) promueven la secreción de citoquinas proinflamatorias activando vías de inflamación, que a su vez afectan la integridad de las uniones intercelulares alterando la barrera intestinal. Lo anterior, permite que los LPS ingresen a la lámina propia y circulación sanguínea produciendo inflamación local y sistémica. Así mismo, las DAG generan efectos nocivos en la morfología y función de la mucosa gastrointestinal lo que podría favorecer el desarrollo de cáncer. Lo anterior, podría deberse a que el consumo de DAG es capaz de aumentar la proliferación de células de la mucosa y el número y proliferación de células madres tumorales en el intestino.

The aim of this review was to present current knowledge about the relationship between high fat diets (HFD), morphological alterations of intestinal mucosa, inflammatory effects and intestinal cancer. The HFD initially produces an increase in the pathogenic microbiota, which reduces quantity and quality of secretion of goblet cells, decreasing the effectiveness of intestinal barrier. Bacteria and their lipopolysaccharides (LPS) stimulate the secretion of proinflammatory cytokines by activating inflammation pathways, which in turn affect the integrity of intercellular junctions by changing intestinal barrier. The above allows the LPS enter to lamina propria and blood circulation producing local and systemic inflammation. Likewise, HFD generate deleterious effects on morphology and function of gastrointestinal mucosa, which could favor the development of cancer. This could be due to the fact that consumption of HFD is capable of increasing proliferation of mucosal cells and number and proliferation of tumor stem cells in the intestine.

Disruption of the Gut Ecosystem by Antibiotics

The intestinal microbiota is a complex ecosystem consisting of various microorganisms that expands human genetic repertoire and therefore affects human health and disease. The metabolic processes and signal transduction pathways of the host and intestinal microorganisms are intimately linked, and abnormal progression of each process leads to changes in the intestinal environment. Alterations in microbial communities lead to changes in functional structures based on the metabolites produced in the gut, and these environmental changes result in various bacterial infections and chronic enteric inflammatory diseases. Here, we illustrate how antibiotics are associated with an increased risk of antibiotic-associated diseases by driving intestinal environment changes that favor the proliferation and virulence of pathogens. Understanding the pathogenesis caused by antibiotics would be a crucial key to the treatment of antibiotic-associated diseases by mitigating changes in the intestinal environment and restoring it to its original state.

Efeito de uma associação de cepas probióticas contendo lactobacillus e bifidobacterium na modulação da microbiota intestinal em pacientes constipados / Effects of association of probiotic strains containing lactobacillus and bifidobacterium on modulation of the intestinal microbiota in constipated patients

Introdução: a constipação é uma doença crônica que afeta a população mundial, podendo ser consequência do desequilíbrio da microbiota intestinal, conhecida como disbiose. Nesse contexto, os probióticos vêm sendo utilizados com o objetivo de promover o seu equilíbrio, a fim de mantê-la saudável (eubiose). Objetivo: avaliar, em um estudo duplo-cego, randomizado, placebo-controlado, se o uso de uma associação de cepas probióticas contendo lactobacillus e bifidobacterium por 28 dias pode modular a microbiota intestinal em pacientes constipados. Método: a atividade da associação de cepas probióticas foi comparada com placebo (maltodextrina) após a suplementação por 28 dias. Os pacientes foram avaliados por meio da análise de metagenômica e da melhora dos sintomas relacionados à constipação. Os dados do perfil da população de microrganismos presentes no intestino dos pacientes foram correlacionados com os resultados da avaliação dos sintomas abdominais e da percepção de bem-estar geral. O aumento do número de evacuações e a melhora do trânsito intestinal foram avaliados durante o estudo. Resultados: as proporções do gênero Bifidobacterium no grupo teste e controle foram 0.45% vs 0.24% no final do estudo, respectivamente (p<0,05). Adicionalmente, a diferença entre os grupos que receberam associação de cepas probióticas contendo lactobacillus e bifidobacterium e placebo permaneceu também significativamente alta com relação às espécies de Lactobacillus (1,21% vs 0,12%) após 28 dias de tratamento (p<0,05). Além disso, os participantes que receberam o probiótico apresentaram uma tendência de melhora sintomática baseada na comparação da sua microbiota e as respostas oriundas da avaliação dos sintomas abdominais e bem-estar geral. Nenhum evento adverso grave foi relatado. Conclusão: a formulação probiótica modulou a microbiota intestinal de forma diferente do placebo nos participantes do estudo. O consumo dos probióticos aumentou significativamente as bactérias benéficas e reduziu as potencialmente maléficas, contribuindo para o equilíbrio da microbiota intestinal.

Introduction: constipation is a chronic disease that affects the world population, being a consequence of the imbalance of the intestinal microbiota, known as dysbiosis. In light of this context, the probiotics have been used to trigger microbiota intestinal balance, in order to keep it healthy (eubiose) Aim: to evaluate in a double-blind, randomized, placebo-controlled study whether the use of association of probiotic strains containing lactobacillus and bifidobacterium for 28 days can modulate the intestinal microbiota of the constipated participants. Methods: the activity of association of probiotic strains was compared to placebo (maltodextrin) after 28 days of consumption. The patients were evaluated by using metagenomics analyses and improved constipation symptoms. The dates of microorganisms population profile into patients gut were correlated with results of abdominal symptoms evaluation and well-being perception. The increase in the number of evacuations and the intestinal transit were evaluated during the study. Results: the proportions of the genus Bifidobacterium in the test groups and the control group were 0.45% vs 0.24% at the end of the study, respectively (p<0.05). Additionally, the difference between the groups that received association of probiotic strains containing lactobacillus and bifidobacterium and the placebo remained higher for species of the genus Lactobacillus (1.21% vs 0.12%) after 28 days of use (p<0.05). Furthermore, the participants who received the probiotic had a tendency to improve symptomatic based on comparisons of their microbiota and the responses provided patients' abdominal symptoms and well-being. There were no reports of serious adverse events during the study. Conclusion: the probiotic formulation modulated the intestinal microbiota differently from the placebo in constipated participants included in this study. The use of this probiotic significantly increased beneficial bacteria and decreased potentially harmful microbes, which contributed to the maintenance of a healthy intestinal microbiota.