Insuflación rectal con ozono en infecciones intestinales / Rectal Insufflation with Ozone in Intestinal Infections

Introducción: Las infecciones intestinales se relacionan con trastornos del sistema inmune y de la microbiota intestinal. Pueden ser recurrentes y producir otras alteraciones intestinales y sistémicas, que empeoran con la terapia antimicrobiana. La ozonoterapia ha sido usada en el tratamiento de infecciones intestinales. Objetivos: Recopilar información sobre los efectos biológicos, terapéuticos y la seguridad de la administración del ozono por insuflación rectal en el tratamiento de las infecciones intestinales. Métodos: Para la búsqueda de información se empleó el motor de búsqueda Google Académico. Se consultaron artículos en las bases de datos PubMed y SciELO de la Biblioteca Virtual de Salud. Además, se realizó una búsqueda general en los idiomas español e inglés, a partir de los artículos más relevantes acerca del estudio. Se utilizaron como palabras clave: infecciones, insuflación, microbioma gastrointestinal, ozono como términos más concretos. En el estudio no se aplicó ninguna restricción acerca del ámbito geográfico ni de la edad. Conclusiones: La aplicación rectal de ozono es segura, tiene acciones biológicas y terapéuticas útiles para tratar las infecciones intestinales. Actúa como inmunomodulador y protector de la microbiota intestinal, lo que permite enfrentar esta problemática de salud desde el punto de vista preventivo, curativo y de rehabilitación de los daños causados, tanto por los gérmenes como por los efectos de los antibióticos(AU)

Introduction: Intestinal infections are related to disorders of the immune system and intestinal microbiota. They can be recurrent and produce other intestinal and systemic alterations, which worsen with antimicrobial therapy. Ozone therapy has been used in the treatment of intestinal infections. Objectives: To compile information on the biological, therapeutic effects and safety of the administration of ozone by rectal insufflation in the treatment of intestinal infections. Methods: Google Scholar search engine was used for searching information. Articles were consulted in PubMed and SciELO databases of the Virtual Health Library. In addition, a general search was carried out in Spanish and English, based on the most relevant articles about the study. The keywords used were infections, insufflation, gastrointestinal microbiome, ozone as more specific terms. No restrictions on geographic area or age were applied in the study. Conclusions: The rectal application of ozone is safe, it has useful biological and therapeutic actions to treat intestinal infections, acting as an immunomodulator and protector of the intestinal microbiota, which allows us to face this health problem from a preventive, curative and rehabilitation point of view of the damage caused, both by germs and by the effects of antibiotics(AU)

Gut microbiota: a new insight into neurological diseases / 中华医学杂志(英文版)

In the last decade, it has become increasingly recognized that a balanced gut microbiota plays an important role in maintaining the health of the host. Numerous clinical and preclinical studies have shown that changes in gut microbiota composition are associated with a variety of neurological diseases, e.g., Parkinson's disease, Alzheimer's disease, and myasthenia gravis. However, the underlying molecular mechanisms are complex and remain unclear. Behavioral phenotypes can be transmitted from humans to animals through gut microbiota transplantation, indicating that the gut microbiota may be an important regulator of neurological diseases. However, further research is required to determine whether animal-based findings can be extended to humans and to elucidate the relevant potential mechanisms by which the gut microbiota regulates neurological diseases. Such investigations may aid in the development of new microbiota-based strategies for diagnosis and treatment and improve the clinical management of neurological disorders. In this review, we describe the dysbiosis of gut microbiota and the corresponding mechanisms in common neurological diseases, and discuss the potential roles that the intestinal microbiome may play in the diagnosis and treatment of neurological disorders.

A new target of precision medicine in sepsis: gut microbiome modified tryptophan metabolism / 中华危重病急救医学

Sepsis is a life-threatening organ dysfunction caused by dysregulated host responses to infection. Despite significant advances in anti-infective, immunomodulatory, and organ function support technologies, the precise and targeted management of sepsis remains a challenge due to its high heterogeneity. Studies have identified disturbed tryptophan (TRP) metabolism as a common mechanism in multiple diseases, which is involved in both immune regulation and the development of multi-organ damages. The rise of research on intestinal microflora has further highlighted the critical role of microflora-regulated TRP metabolism in pathogen-host interactions and the "cross-talk" among multi-organs, making it a potential key target for precision medicine in sepsis. This article reviews TRP metabolism, the regulation of TRP metabolism by the intestinal microflora, and the characteristics of TRP metabolism in sepsis, providing clues for further clinical targeting of TRP metabolism for precision medicine in sepsis.

Metabolitos bioactivos generados por la disbiosis intestinal y sus implicaciones fisiopatológicas en la enfermedad cardiovascular / Bioactive metabolites generated by intestinal dysbiosis and their pathophysiological implications in cardiovascular disease

Introducción: La disbiosis conocida como la alteración de la relación simbiótica entre la microbiota intestinal y el huésped están implicados en la patogenia de la enfermedad cardiovascular aterosclerótica. Objetivo: Realizar una revisión documental sobre los mecanismos fisiopatológicos que relacionan los metabolitos bioactivos generados por la disbiosis intestinal con el desarrollo y progresión de la enfermedad cardiovascular aterosclerótica. Métodos: Se utilizó el motor de búsqueda Google Académico y se consultaron artículos de libre acceso en las bases de datos Pubmed, SciELO, Lilacs, Cumed y Hinari desde septiembre 2020 hasta el mes de marzo 2021. Las palabras clave utilizadas para esta revisión fueron:microbioma, microbiota intestinal, disbiosis, aterosclerosis, enfermedad cardiovascular y sus equivalentes en inglés, según el descriptor de Ciencias de la Salud (DeCS). Se consideraron artículos originales, de revisión, revisiones sistemáticas y metaanálisis posteriores al año 2015. Se revisaron un total de 73 artículos. Desarrollo: Las relaciones fisiopatológicas entre la disbiosis intestinal y las enfermedades cardiovasculares son complejas, ya que se influyen mutuamente a través de los sus toxinas endógenas (metabolitos bioactivos), el sistema circulatorio, las respuestas inmunitarias y los cambios metabólicos. Las investigaciones futuras deberían centrarse en dilucidar los actores moleculares subyacentes e identificar si las vías que interconectan la disbiosis intestinal con la ECA son causales, correlacionales o consecuentes. Conclusiones: La evidencia acumulada sostiene que la disbiosis de la microbiota intestinal está involucrada en la síntesis de metabolitos proaterogénicos los cuales modulan los mecanismos implicados en la fisiopatología de la ECA(AU)

Introduction: Dysbiosis is known as the alteration of the symbiotic relationship between the intestinal microbiota and the host is involved in the pathogenesis of atherosclerotic cardiovascular disease. Objective: To carry out a documentary review on the pathophysiological mechanisms that relate the bioactive metabolites generated by intestinal dysbiosis with the development and progression of atherosclerotic cardiovascular disease. Methods: The Google Scholar search engine was used and free access articles were consulted in Pubmed, SciELO, Lilacs, Cumed and Hinari databases from September 2020 to March 2021. The keywords used for this review were microbiome, gut microbiota, dysbiosis, atherosclerosis, cardiovascular disease and their English equivalents, according to the Health Sciences (DeCS) descriptor. Original articles, review articles, systematic reviews and meta-analyses after 2015 were considered. A total of 73 articles were reviewed. Findings: The pathophysiological relationships between intestinal dysbiosis and cardiovascular diseases are complex, since they influence each other through their endogenous toxins (bioactive metabolites), the circulatory system, immune responses and metabolic changes. Future research should focus on elucidating the underlying molecular players and on identifying whether the pathways that interconnect gut dysbiosis with ACE are causal, correlational, or consequential. Conclusions: The accumulated evidence supports that the dysbiosis of the intestinal microbiota is involved in the synthesis of proatherogenic metabolites which modulate the mechanisms involved in the pathophysiology of ACE(AU)

Gut microbiome in neuropsychiatric disorders / O microbioma intestinal nas doenças neuropsiquiátricas

ABSTRACT Background: Neuropsychiatric disorders are a significant cause of death and disability worldwide. The mechanisms underlying these disorders include a constellation of structural, infectious, immunological, metabolic, and genetic etiologies. Advances in next-generation sequencing techniques have demonstrated that the composition of the enteric microbiome is dynamic and plays a pivotal role in host homeostasis and several diseases. The enteric microbiome acts as a key mediator in neuronal signaling via metabolic, neuroimmune, and neuroendocrine pathways. Objective: In this review, we aim to present and discuss the most current knowledge regarding the putative influence of the gut microbiome in neuropsychiatric disorders. Methods: We examined some of the preclinical and clinical evidence and therapeutic strategies associated with the manipulation of the gut microbiome. Results: targeted taxa were described and grouped from major studies to each disease. Conclusions: Understanding the complexity of these ecological interactions and their association with susceptibility and progression of acute and chronic disorders could lead to novel diagnostic biomarkers based on molecular targets. Moreover, research on the microbiome can also improve some emerging treatment choices, such as fecal transplantation, personalized probiotics, and dietary interventions, which could be used to reduce the impact of specific neuropsychiatric disorders. We expect that this knowledge will help physicians caring for patients with neuropsychiatric disorders.

RESUMO Antecedentes: Os transtornos neuropsiquiátricos são uma importante causa de morte e invalidez no mundo. Os mecanismos subjacentes a esses transtornos incluem uma constelação de etiologias estruturais, infecciosas, imunológicas, metabólicas e genéticas. Avanços nas técnicas de sequenciamento do DNA têm demonstrado que a composição do microbioma entérico é dinâmica e desempenha um papel fundamental não apenas na homeostase do hospedeiro, mas também em várias doenças. O microbioma entérico atua como mediador na sinalização das vias metabólica, neuroimune e neuroendócrina. Objetivo: Apresentar os estudos mais recentes sobre a possível influência do microbioma intestinal nas diversas doenças neuropsiquiátricas e discutir tanto os resultados quanto a eficácia dos tratamentos que envolvem a manipulação do microbioma intestinal. Métodos: foram examinadas algumas das evidências pré-clínicas e clínicas e estratégias terapêuticas associadas à manipulação do microbioma intestinal. Resultados: os táxons-alvo foram descritos e agrupados a partir dos principais estudos para cada doença. Conclusões: Entender a fundo a complexidade das interações ecológicas no intestino e sua associação com a suscetibilidade a certas doenças agudas e crônicas pode levar ao desenvolvimento de novos biomarcadores diagnósticos com base em alvos moleculares. Além disso, o estudo do microbioma intestinal pode auxiliar na otimização de tratamentos não farmacológicos emergentes, tais como o transplante de microbiota fecal, o uso de probióticos e intervenções nutricionais personalizadas. Dessa forma, terapias alternativas poderiam ser usadas para reduzir o impacto dos transtornos neuropsiquiátricos na saúde pública. Esperamos que esse conhecimento seja útil para médicos que cuidam de pacientes com diversos transtornos neuropsiquiátricos.

Research progress on the regulation of mammalian energy metabolism by the circadian clock system and gut microbiota / 生理学报

The mammalian internal circadian clock system has been evolved to adapt to the diurnal changes in the internal and external environment of the organism to regulate diverse physiological functions, such as the sleep-wake cycle and feeding rhythm, thereby coordinating the rhythmic changes of energy demand and nutrition supply in each diurnal cycle. The circadian clock regulates glucose metabolism, lipid metabolism, and hormones secretion in diverse tissues and organs, including the liver, skeletal muscle, pancreas, heart, and vessels. As a special "organ" of the host, the gut microbiota, together with the intestinal microenvironment (tissues, cells, and metabolites) in a co-evolutionary process, constitutes a micro-ecosystem and plays an important role in the process of nutrient digestion and absorption in the intestine of the host. In recent years, accumulating evidence indicates that the compositions, quantities, colonization, and functional activities of the gut microbiota exhibit significant circadian variations, which are closely related to the changes of various physiological functions under the regulation of host circadian clock system. In addition, several studies have shown that the gut microbiota can produce many important metabolites such as the short-chain fatty acids through the degradation of indigestive dietary fibers. A portion of gut microbiota-derived metabolites can regulate the circadian clock system and metabolism of the host. This article mainly discusses the interaction between the host circadian clock system and the gut microbiota, and highlights its influence on energy metabolism of the host, providing a novel clues and thought for the prevention and treatment of metabolic diseases.

Role and change of the gut microbiota after bariatric surgery / 中华胃肠外科杂志

Gut microbiota have been validated to play a pivotal role in metabolic regulation. As the most effective treatment for obesity and related comorbidities, bariatric surgery has been shown to result in significant alterations to the gut microbiota. Literature have recently suggested temporal and spatial features of alterations to the intestinal bacteria following bariatric surgery, which is possibly attributed to the gut adaptation to the surgical modification on the gastrointestinal tract. More importantly, the gut microbiota have been appreciated as a critical contributor to the metabolic improvements following bariatric surgery. Although not fully elucidated, the underlying mechanisms are associated with the molecular pathways mediating the crosstalk between gut microbiota and host . On the other hand, change of the gut microbiota has been found to be related to the prognosis of patients receiving bariatric surgery. Some studies even point out negative effects of the gut microbiota on certain surgical complications . In this review, we summarize the characteristics of alterations to the gut microbiota following bariatric surgery as well as its relevant impacts to better understand the role of gut microbiota in bariatric surgery.

Fecal transplantation can alleviate tic severity in a Tourette syndrome mouse model by modulating intestinal flora and promoting serotonin secretion / 中华医学杂志(英文版)

BACKGROUND@#: Tourette syndrome (TS) is a neuropsychiatric disorder with onset in childhood that warrants effective therapies. Gut microbiota can affect central physiology and function via the microbiota-gut-brain axis. Therefore, the gut microbiota plays an important role in some mental illnesses. A small clinical trial showed that fecal microbiota transplantation (FMT) may alleviate TS symptoms in children. Herein, FMT effects and mechanisms were explored in a TS mouse model.@*METHODS@#: TS mice model (TSMO) (n = 80) were established with 3,3'-iminodipropionitrile, and 80 mice were used as controls. Mice were grouped into eight groups and were subjected to FMT with feces from children or mice with or without TS, or were given probiotics. Fecal specimens were collected 3 weeks after FMT. 16S rRNA sequencing, behavioral observation, and serum serotonin (5-HT) assay were performed. Differences between groups were analyzed using Mann-Whitney U test and Kolmogorov-Smirnov (KS) tests.@*RESULTS@#: A total of 18 discriminative microbial signatures (linear discriminant analysis score > 3) that varied significantly between TS and healthy mice (CONH) were identified. A significant increase in Turicibacteraceae and Ruminococcaceae in TSMO after FMT was observed (P  < 0.05). Compared with non-transplanted TSMO, the symptoms of those transplanted with feces from CONH were alleviated (W = 336, P = 0.046). In the probiotic and FMT experiments, the serum 5-HT levels significantly increased in TSMO that received probiotics (KS = 1.423, P = 0.035) and in those transplanted with feces from CONH (W = 336.5, P = 0.046) compared with TSMO without transplantation.@*CONCLUSIONS@#: This study suggests that FMT may ameliorate TS by promoting 5-HT secretion, and it provides new insights into the underlying mechanisms of FMT as a treatment for TS.

Microbiota intestinal y su relación con agentes oportunistas vinculados a las epidemias / Gut microbiota and its relationship with opportunistic agents linked to epidemics

Resumen Existen epidemias silenciosas asociadas al estrés y a los malos hábitos de alimentación, tan importantes como las epidemias tradicionales asociadas a la pobreza, a problemas geográficos y climáticos. Numerosos estudios se suman al importante papel de un patrón estable de la microbiota intestinal que favorece el estado saludable en los seres humanos y por lo tanto, su posible implicación en la incidencia y prevalencia de enfermedades que pueden convertirse en epidémicas. En esta revisión se analiza el estado actual de la relación entre los factores demográficos, geográficos, ambientales, patrones de consumo de alimentos con la microbiota intestinal y la aparición de epidemias de origen microbiano, metabólico e inmunológico. Se apoya la iniciativa promovida internacionalmente para la creación de plataformas metagenómicas que contribuyan al estudio del patrón de la microbiota intestinal, el seguimiento epidemiológico y la prevención de las enfermedades epidémicas asociadas con su alteración, así como el diseño de métodos rápidos y económicos para la complementación de estos estudios.

Abstract Silent epidemics associated with stress and unhealthy eating habits are as important as traditional epidemics related to poverty, geographical and climate problems. Many studies incorporate the important role of a stable pattern of gut microbiota that favours the human health status and therefore, its possible implication in incidence and prevalence of diseases that can become epidemics. In this review, the current state-of-art is analysed in terms of relationship between demographic, geographic, environmental factors, and habits with the gut microbiota pattern and the onset of epidemics of microbial, metabolic and immunological origin. The internationally promoted initiative for the creation of metagenomic platforms contributing to studies of the gut microbiota pattern for the epidemiological monitoring and prevention of epidemic diseases associated with its alteration is fostered, as well as the design of rapid and economic methods to complement these studies.

Resumo Existem epidemias silenciosas associadas ao estresse, maus hábitos alimentares, tão importantes quanto as epidemias tradicionais associadas à pobreza, problemas geográficos e climáticos. Numerosos estudos contribuem para o importante papel de um padrão estável de microbiota intestinal que favorece o estado saudável em seres humanos e, portanto, sua possível comprometimento na incidência e prevalência de doenças que podem se tornar epidêmicas. Esta revisão analisa o estado atual da relação entre fatores demográficos, geográficos, ambientais, padrões de consumo de alimentos com a microbiota intestinal e o aparecimento de epidemias de origem microbiana, metabólica e imunológica. É fornecido apoio à iniciativa promovida internacionalmente para a criação de plataformas metagenômicas que contribuam para o estudo do padrão da microbiota intestinal, monitoramento epidemiológico e prevenção de doenças epidêmicas associadas à sua alteração, bem como o desenho de métodos rápidos e baratos para a complementação desses estudos.

Lactancia materna y COVID-19 / Breastfeeding and COVID-19

Resumen La pandemia de enfermedad por coronavirus 2019 (COVID-19) ha afectado a todas las dimensiones de la atención en salud, entre ellas el aseguramiento de la lactancia materna exclusiva y su promoción. El riesgo de contagio y las consecuencias de la pandemia han provocado preocupación entre las futuras madres o las que se ya encuentran lactando debido al riesgo de una posible transmisión del virus a través de la leche materna. Aunque aún no se ha detectado el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) activo en la leche materna. El miedo al contagio ha favorecido las políticas de aislamiento madre-hijo. Hasta el momento no existe evidencia de transmisión vertical y el riesgo de transmisión horizontal en el lactante es similar al de la población general. En lactantes con COVID-19 la lactancia materna incluso puede cambiar favorablemente el curso clínico de la enfermedad.

Abstract The COVID-19 pandemic has affected the health attention in all dimensions, one of them, the exclusive breastfeeding assurance and her promotion. The high risk of contagion and the pandemic consequences have raised a number of concerns in future mothers or those who are breastfeeding because of the risk of a possible transmission of the virus through breast milk. Although SARS-CoV2 has no evidence of being active on breast milk, the fear of contagion has favored mother-child isolation policies. At this point, there are no evidence of vertical transmission and the risk of horizontal transmission in the infant is similar to the general population. Breastfeeding in newborn with COVID-19, can even favorably change the clinical course of the disease.

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.

Intestinal Microbiota and Cardiovascular Diseases

Abstract Recently, gut microbiota has emerged as an important mediator of several diseases such as diabetes, atherosclerosis, arterial hypertension, obesity, cancers and neuropsychiatric diseases including Alzheimer, autism and depression. Intestinal microbiota is formed by bacteria, fungi and viruses and its main function is to facilitate the absorption and metabolism of foods (protein, fat and carbohydrate). One example of the multiple actions of the gut microbiota is the bidirectional relationship between the intestine and the brain, the so-called "gut/brain axis". Furthermore, metabolites produced by gut microbiota can induce effects locally or at distance, which suggests that the intestine is an endocrine organ. Given the participation of the gut microbiota in several diseases, there is great interest in strategies that may positively affect the gut flora and prevent or even treat diseases. Among these strategies, lifestyle change, but specially diet modulation has gained importance. In this article, we review the mechanisms through which intestinal microbiota participates in cardiovascular diseases and possible therapeutic interventions.

Implicaciones de la microbiota intestinal en las enfermedades crónicas del hígado / Implications of the intestinal microbiota in the chronic liver diseases

RESUMEN La microbiota se refiere al conjunto de todos los de microorganismos que se localizan de manera normal en distintos sitios de los cuerpos de los seres vivos pluricelulares, tales como el cuerpo humano. Las modificaciones del eje intestino-hígado se ha convertido en la actualidad en un grave problema científico al haberse encontrado en diversas investigaciones, que esta microbiota está relacionada con el daño hepático con independencia de la causa de la lesión hepática. Se realizó una revisión sistemática sobre las implicaciones demamicrobiota intestinal en las enfermedades hepáticas. Se realizó una revisión de artículos científicos publicados entre 2012 y 2018 en diversas bases de datos en línea. Se presenta el conocimiento existente hasta el momento sobre la microbiota intestinal en pacientes portadores de enfermedades hepáticas, con hincapié en las hepatitis C y la cirrosis hepática. La composición de microbiota de intestino estuvo asociada con el perfil inflamatorio y marcadores de fibrosis hepática, las que mejoraron con el tratamiento de antivirales de acción directa aunque las medidas de permeabilidad intestinal e inflamación permanecían inalteradas. Se reporta mejoría de los pacientes portadores de hepatitis viral tipo C, con antivirales de acción directa la cual estuvo asociada con modificaciones de la microbiota intestinal, que se correlacionó con mejoría en la fibrosis e inflamación hepática, los avances en este campo abren nuevas perspectivas en la biomedicina (AU).

SUMMARY Microbiota refers to the whole of microorganisms located in a normal way in different places of the bodies of pluricelular living beings, like the human body. The modifications of the axis intestine-liver have become a serious scientific problem, because in different researches researchers have found that this microbiota is related to hepatic damage depending on the cause of this hepatic lesion. To carry out a systematic review on the implication of intestinal macrobiota in liver diseases. The scientific articles published in the period 2012-2018 in different databases on line were reviewed. A total of 26 bibliographic sources were used, original articles and reviews. The authors present knowledge existent up to the moment on intestinal microbiota in patients who have liver diseases, making emphasis on hepatitis C and hepatic cirrhosis. The composition of the intestine microbiota was associated to an inflammatory and markers of hepatic fibrosis that improved with the treatment of direct action antivirals although the measures of intestinal permeability and inflammation remained inalterably. It is reported an improvement of patients carriers of viral hepatitis type C with the use direct action retrovirals, what was linked to modifications in the intestinal microbiota, and correlated to an improvement of fibrosis and liver inflammation; the advances obtained in this field open new perspectives in biomedicine (AU).

Microbiota intestinal y trastornos del comportamiento mental / Intestinal microbiota and mental behavior disorders

Introducción: Se actualiza la relación del eje microbiota-intestino-cerebro con enfermedades neurológicas y psiquiátricas, en particular en trastornos del comportamiento en la infancia y adultos postulados en años recientes. Objetivo: Analizar la participación del eje microbiota-intestino-cerebro con alteraciones del comportamiento humano, con preferencia en la infancia y el papel de la disbiosis como factor determinante. Métodos: Se revisaron las publicaciones sobre el tema en español e inglés en bases de datos de PubMed, Google Scholar, SciELO y Latindex desde el 2015 hasta el 30 septiembre de 2019. Resultados: Se actualizaron los criterios sobre el papel del eje microbiota-intestino-cerebro, posibles vías de acción y asociación con disbiosis y otros factores, desencadenados por alteración de la microbiota intestinal y su influencia en los trastornos del comportamiento mental, representados por el espectro autista, hipoactividad/ hiperexcitabilidad, ansiedad y depresión. Consideraciones finales: Los conocimientos alcanzados en el último decenio en estudios experimentales en ratones y la aplicación de sus resultados en humanos, sobre el papel del eje bidireccional microbiota-intestino-cerebro y sus relaciones con el equilibrio y desequilibrio de la microbiota intestinal, argumentan la posible participación del eje referido en el neurodesarrollo, afectación cerebral y neuromodulación y en especial en trastornos de conducta, como el espectro autista y otras afecciones analizadas(AU)

Introduction: The microbiota-gut-brain axis´ relation with neurological and psychiatric diseases is updated, in particular in behavioral disorders in children and adults postulated in recent years. Objective: To analyze the participation of the microbiota-gut-brain axis in alterations of human behavior, with a preference in childhood and the role of dysbiosis as a determining factor. Methods: It was reviewed the literature on the subject in Spanish and English in databases of PubMed, Google Scholar, SciELO and Latindex from 2015 until September 30, 2019. Results: The criteria were updated on the role of the microbiota-gut-brain axis, possible ways of action and association with dysbiosis and other factors triggered by alteration of the intestinal microbiota and its influence on mental behavior disorders represented by the autism spectrum, hypoactivity/ hyperexcitability, anxiety and depression. Conclusions: Knowledge achieved in the last decade in experimental studies in mice and the application of their results in humans, the role of the microbiota-gut-brain bi-directional axis and its relations with the balance and imbalance of the intestinal microbiota argue on the possible involvement of the referred axis in neurodevelopment, brain affectation and neuromodulation, and especially in behavioral disorders, such as autism spectrum disorders and other conditions analyzed(AU)

Investigación traslacional en microbioma (InTraMic): un área de interés común y creciente en el IMTIB, Hospital Italiano e Instituto Universitario / Translational research in microbiome (InTraMic): an area of common and growing interest at IMTIB, Hospital Italiano and Instituto Universitario

Se estima que aproximadamente 100 trillones de microorganismos (incluidos bacterias, virus y hongos) residen en el intestino humano adulto y que el total del material genético del microbioma es 100 veces superior al del genoma humano. Esta comunidad, conocida como microbioma se adquiere al momento del nacimiento a través de la flora comensal de la piel, vagina y heces de la madre y se mantiene relativamente estable a partir de los dos años desempeñando un papel crítico tanto en el estado de salud como en la enfermedad. El desarrollo de nuevas tecnologías, como los secuenciadores de próxima generación (NGS), permiten actualmente realizar un estudio mucho más preciso de ella que en décadas pasadas cuando se limitaba a su cultivo. Si bien esto ha llevado a un crecimiento exponencial en las publicaciones, los datos sobre las poblaciones Latinoamérica son casi inexistentes. La investigación traslacional en microbioma (InTraMic) es una de las líneas que se desarrollan en el Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB). Esta se inició en 2018 con la línea de cáncer colorrectal (CCR) en una colaboración con el Colorectal Cancer Research Group del Leeds Institute of Medical Research en el proyecto Large bowel microbiome disease network: Creation of a proof of principle exemplar in colorectal cancer across three continents. A fines de 2019 se cumplió el objetivo de comprobar la factibilidad de la recolección, envío y análisis de muestras de MBF en 5 continentes, incluyendo muestras provenientes de la Argentina, Chile, India y Vietnam. Luego de haber participado de capacitaciones en Inglaterra, se ha cumplido con el objetivo de la etapa piloto, logrando efectivizar la recolección, envío y análisis metagenómico a partir de la secuenciación de la región V4 del ARNr 16S. En 2019, la línea de enfermedad de hígado graso no alcohólico se sumó a la InTraMic iniciando una caracterización piloto en el marco de una colaboración con el laboratorio Novartis. Los resultados de ese estudio, así como el de cáncer colorrectal, están siendo enviados a publicación. En 2020, con la incorporación de la línea de trasplante alogénico de células progenitoras hematopoyéticas, fue presentado un proyecto para un subsidio del CONICET que ha superado la primera etapa de evaluación. En el presente artículo se brinda una actualización sobre la caracterización taxonómica de microbioma y se describen las líneas de investigación en curso. (AU)

It is estimated that approximately 100 trillion microorganisms (including bacteria, viruses, and fungi) reside in the adult human intestine, and that the total genetic material of the microbiome is 100 times greater than that of the human genome. This community, known as the microbiome, is acquired at birth through the commensal flora of the mother's skin, vagina, and feces and remains relatively stable after two years, playing a critical role in both the state of health and in disease. The development of new technologies, such as next-generation sequencers (NGS), currently allow for a much more precise study of it than in past decades when it was limited to cultivation. Although this has led to exponential growth in publications, data on Latin American populations is almost non-existent. Translational research in microbiome (InTraMic) is one of the lines developed at the Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB). This started in 2018 with the Colorectal Cancer Line (CRC) in a collaboration with the Colorectal Cancer Research Group of the Leeds Institute of Medical Research in the project "Large bowel microbiome disease network: Creation of a proof of principle exemplar in colorectal cancer across three continents". At the end of 2019, the objective of verifying the feasibility of collecting, sending and analyzing MBF samples on 5 continents, including samples from Argentina, Chile, India and Vietnam, was met. After having participated in training in England, the objective of the pilot stage has been met, achieving the collection, delivery and metagenomic analysis from the sequencing of the V4 region of the 16S rRNA. In 2019, the non-alcoholic fatty liver disease line joined InTraMic, initiating a pilot characterization in the framework of a collaboration with the Novartis laboratory. The results of that study, as well as that of colorectal cancer, are being published. In 2020, with the incorporation of the allogeneic hematopoietic stem cell transplantation line, a project was presented for a grant from the CONICET that has passed the first stage of evaluation. This article provides an update on the taxonomic characterization of the microbiome and describes the lines of ongoing research. (AU)

Relación entre microbiota intestinal, epigenética y exposoma en la salud materno infantil / Relation between intestinal microbiota, epigenetics and exposome in mother-child health

Introducción: El exposoma, la epigenética y la microbiota de un individuo son categorías que se interrelacionan y pueden contribuir a una mejor comprensión del proceso salud enfermedad. Objetivo: Exponer la relación entre las categorías mencionadas con enfoque biopsicosocial. Métodos: Búsqueda bibliográfica en Medline, Pubmed, Scielo, LILACS y Cochrane en los últimos cinco años en idioma inglés y español, sobre la relación entre nutrición y aparición de enfermedades, el eje intestino cerebro, la correspondencia entre epigenética y el exposoma y la microbiota intestinal y su relación con algunas afecciones. Resultados: La alimentación adecuada de la madre, en calidad y cantidad, es un seguro de salud para la vida futura del hombre. El eje intestino cerebro puede afectarse por factores de riesgo, de ahí la importancia de regular su funcionamiento para la prevención de enfermedades como la depresión, síndrome de ansiedad, sobrepeso, y otras. El 10 por ciento del riesgo de padecer enfermedades crónicas puede deberse a factores genéticos pero se desconoce que muchas exposiciones humanas al ambiente, podrían iniciar procesos de enfermedad en el futuro. El exposoma es una herramienta útil para evaluar factores de riesgo de enfermedades generadas por el medio ambiente: exposición a productos químicos y contaminantes; el estilo de vida, el nivel socioeconómico y el entorno social de un individuo. Consideraciones finales: La ruptura del equilibrio entre la microbiota intestinal, la epigenética y el exposoma está relacionada con la etiopatogenia de diversas enfermedades, con las características individuales del ser humano y su relación con el medio ambiente(AU)

Introduction: Exposome, epigenetics and microbiota of an individual are categories that are interrelated and can contribute to a better understanding of the health-sickness process. Objective: To deepen the comprehensive analysis of the mentioned categories with a biopsychosocial approach. Methods: A bibliographic search in Medline, Pubmed, Scielo, LILACS and Cochrane databases was made in the last five years in English and Spanish, on the relation between nutrition and diseases onset, the intestine-brain axis, the correspondence between epigenetics and the exposome, and intestinal microbiota and its relation with some conditions. Results: The proper feeding of the mother in quality and quantity is a health insurance for the future life of a person. The intestine -brain axis can be affected by risk factors, hence the importance of regulating its functioning for the prevention of diseases such as depression, anxiety syndrome, overweight, and others. 10 percent of the risk of chronic diseases may be due to genetic factors but it is unknown that many human exposures to the environment could initiate disease processes in the future. The exposome is a useful tool to evaluate risk factors for diseases generated by the environment: exposure to chemicals and contaminants, lifestyle, socioeconomic status and social environment of an individual. Final considerations: The rupture of the equilibrium between intestinal microbiota, epigenetics and exposome is related to the etiopathogenesis of various diseases, with the individual characteristics of human beings and their relationship with the environment(AU)

Microbiota intestinal y salud en humanos: obesidad y diabetes mellitus tipo 2 / Gut microbiota and healthy in human: obesity and type 2 diabetes mellitus

RESUMEN Introducción La cantidad y la diversidad bacteriana intestinal están relacionadas con las enfermedades metabólicas e inflamatorias. El objetivo de este trabajo fue caracterizar la composición de la microbiota intestinal en heces y su relación con variables bioquímicas y el patrón de consumo de alimentos en individuos sanos, obesos y pacientes con diabetes mellitus tipo 2, en Mallorca (España). Métodos Las bacterias en heces se caracterizaron por PCR tiempo real. El ADN se aisló a partir de sujetos sanos (23), obesos (no diabéticos) (24) y diabéticos tipo 2 (no obesos) y se amplificó con cebadores específicos para identificar Roseburia, Clostridium leptum, Lactobacillus y Clostridium coccoides-Eubacterium rectale (Firmicutes); Prevotella y Bacteroides (Bacteroidetes); Bifidobacterium (Actinobacteria) y el cebador Universal (para total de bacterias), para la amplificación de la región V4 del gen 16S rRNA. Los resultados se analizaron estadísticamente utilizando SPSS v.21. Resultados En una población rural y urbana de Baleares, se detectaron niveles de insulina significativamente superiores en obesos (12,2 + 1,3 md/dL). En diabéticos, los niveles de triglicéridos, glucosa en sangre, hemoglobina glucosilada y albúmina en orina fueron superiores que en controles y obesos (por encima del rango normal). La mayor dispersión de las variables bioquímicas en sangre se identificó con: Clostridium coccoide-Eubacterium rectale, Bacteroides y Bifidobacterium, como posibles marcadores en obesos y diabéticos y Prevotella y Lactobacillus, como marcadores de salud. El contenido total de bacterias es mayor en controles y la relación entre reinos bacterianos es menor en este grupo. Los patrones de consumo de alimentos fueron diferentes en los tres grupos lo cual está relacionado con la variación en los patrones bacterianos. Conclusión La variabilidad en el consumo de alimentos estuvo relacionada con cinco marcadores bacterianos principales que contribuyeron a la mayor variabilidad de marcadores bioquímicos entre grupos de sujetos: Clostridium coccoide-Eubacterium rectale, Bacteroides, Bifidobacterium, Prevotella y Lactobacillus, en una población de Mallorca (España). Gut microbiota and healthy in human: obesity and type 2 diabetes mellitus.

ABSTRACT Introduction The amount and bacterial diversity in the bowel are associated to metabolic and inflammatory diseases. The aim was to characterize the gut microbiota composition in faeces and food consumption pattern in healthy, obese and Type 2 diabetes mellitus subjects from Majorca (Spain). Methods Bacteria in faeces were characterized by Real-time PCR. DNA was isolated from healthy subjects (23), obese patients (not diabetic) (24) and type 2 diabetic patients (12) and amplified with specific primers for the identification of Roseburia, Clostridium leptum, Lactobacillus and Clostridium coccoides-Eubacterium rectale (Firmicutes); Prevotella and Bacteroides (Bacteroidetes); Bifidobacterium (Actinobacteria); and Universal primer (for all bacteria), referred to amplification of 16S rRNA gene V4 region. Results were statistically analyzed by SPSS v.21. Results A rural and urban population from Balearic Islands was tested. The insulin levels were highest in obese group (12.2 + 1.3 md/dL) while the triglyceride, blood glucose, glycosylated haemoglobin and urine albumin levels were highest in diabetic group. The major dispersion of the blood variables was identified to a bacteria core: Clostridium coccoide-Eubacterium rectale, Bacteroides and Bifidobacterium as possible markers for obese and diabetic patients; and Prevotella and Lactobacillus levels as markers of health. The total amount of bacteria is the highest in control group, such as the ratio between phyla is the lowest. The food consumptiom patterns were different among which is related to the variation in the bacterial patterns. Conclusion The variability in the foods consumption among groups was related to five bacterial markers which contributed to the major variability in blood markers: Clostridium coccoide-Eubacterium rectale, Bacteroides, Bifidobacterium, Prevotella y Lactobacillus; in a population from Majorca, Spain.

Microbiota intestinal y salud infantil / Intestinal microbiota and child health

Introducción: la microbiota intestinal participa en eventos de homeostasis e inmunidad intestinal de trascendencia para la salud humana. Sus interacciones con el ecosistema intestinal, participación en distintas enfermedades, y el valor de los probióticos y prebióticos son revisados. Objetivo: evaluar los conocimientos de la literatura médica en las últimas décadas sobre los principales aspectos de la microbiota intestinal, su relación con la inmunidad, y beneficios de probióticos y prebióticos como terapia en distintas afecciones intestinales y extraintestinales. Métodos: se realiza búsqueda en bases de datos de PubMed, Scielo, Redalycs, Latindex de publicaciones acerca de microbiota intestinal, revisiones sistemáticas de probióticos y libros afines. Desarrollo: se revisan las características de los procesos de colonización, desarrollo, funciones y composición de la microbiota intestinal, su inmunidad y relación con el hígado. Se actualizan los principios de la terapia con probióticos y prebióticos, y sus distintas indicaciones en enfermedades digestivas. Conclusiones finales: se evidencia el papel del microbioma intestinal y su relación con el ecosistema intestinal, los mecanismos participantes y el consiguiente desarrollo de su inmunidad, resaltando el rol de la lactancia materna para un adecuado proceso de implantación de la microbiota. Se analiza el uso de probióticos y prebióticos, y su eficacia en distintas enfermedades digestivas(AU)

Introduction: the intestinal microbiota is involved in homeostasis and intestinal immunity events which are crucial to human health. An overview is provided of its interactions with the intestinal ecosystem, its participation in various conditions, and the value of probiotics and prebiotics. Objective: evaluate the information contained in the medical literature published in the past decades about the main features of the intestinal microbiota, its relationship to immunity, and the beneficial therapeutic action of probiotics and prebiotics in various intestinal and extra-intestinal disorders. Methods: a search was conducted in the databases PubMed, SciELO, Redalyc and Latindex for publications about the intestinal microbiota, systematic reviews about probiotics, and related books. Results: examination was carried out of the characteristics of colonization processes, development, functions and composition of the intestinal microbiota, as well as its immunity and relationship to the liver. Updating was also performed about the principles underlying the therapy with probiotics and prebiotics, and their various indications for digestive diseases. Final conclusions: a description is provided of the role of the intestinal microbiota and its relationship to the intestinal ecosystem, the mechanisms involved and the consequent development of its immunity, pointing out the role of breastfeeding for an adequate process of implantation of the microbiota. An analysis is made of the use of probiotics and prebiotics, and their efficacy for various digestive diseases(AU)

Colon epithelial cells luminal environment and physiopathological consequences: impact of nutrition and exercise

The colonic epithelial cells represent a border between the colon luminal content, containing notably bacteria and a complex mixture of compounds, and the"milieu interieur"as defined by the French physiologist Claude Bernard.The physical-chemical composition of the luminal content, including luminal pH and bacterial metabolite, that obviousl y is not constant, is modified for instance according to the diet. Data obtained recently indicate that physical exercise may also modify the colonic luminal content. Evidence has indicated that modification of the luminal content characteristics has, indeed, consequences for the colonic epithelial cells, notably in terms of energy metabolism and DNA integrity. Although such alterations impact presumably the homeostatic process of the colonic epithelium renewal and the epithelial barrier function, their contribution to pathological processes like mucosal inflammation, pre-neoplasia, and neoplasia remains partly elusive. Open questions remain regarding the individual and collective roles of luminal changes, particularly in a long-term perspective. These questions are related particularly to the capacity of the bacterial metabolites to cross the mucus layer before entering the colonocytes, to the concentrations of metabolites in proximity of the colonic crypt stem cells, and to the capacity of colonocytes to detoxicate deleterious compounds, to take up and utilize beneficial compounds.