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.

Can sexual transmission support the enzootic cycle of Trypanosoma cruzi?

BACKGROUND Trypanosoma cruzi circulates in sylvatic habitats, mainly through blood-feeding triatomines, although other routes also contribute to its dispersion. Sexual transmission of T. cruzi is an understudied topic, especially among wild mammals. Because of the difficulties inherent to field work, experimentally infected mice are frequently used to evaluate the transmission of T. cruzi. OBJECTIVE This study aimed to evaluate the sexual transmission of T. cruzi in acutely infected mice. METHODS Male and female mice in the acute phase of Chagas disease were mated with naïve partners. Then, parasitological tests, immunohistochemistry, serological assays, and polymerase chain reaction (PCR) assays were used to detect infection. FINDINGS Parasitological analysis showed trypomastigotes in the blood of 20% of the naïve mice after mating with infected partners. Serological assays detected anti-T. cruzi antibodies in all naïve females mated with infected males and in 60% of naïve males mated with infected females. PCR showed T. cruzi nDNA bands for all naïve mice mated with infected partners. The possibility of sexual transmission was also confirmed by visualisation of amastigotes in the testes. MAIN CONCLUSIONS Our results demonstrate that sexual transmission of T. cruzi is an ordinary event that may contribute to maintenance of the parasite's enzootic cycle.

Sexual transmission of American trypanosomiasis in humans: a new potential pandemic route for Chagas parasites

BACKGROUND The Trypanosoma cruzi infection endemic in Latin America has now spread to several countries across four continents; this endemic involves triatomine vector-free protists. We hypothesised that the sexual transmission of T. cruzi contributes to the ongoing spread of Chagas disease. OBJECTIVES A short-term longitudinal study was conducted to evaluate this hypothesis. METHODS The study population comprised 109 subjects from four families, among whom 21 had been diagnosed with acute Chagas disease by direct parasitological analysis. Blood mononuclear cells and serum samples were obtained from each study subject once per year for three consecutive years. Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence serological examinations were used to detect specific T. cruzi antibodies. Polymerase chain reaction of T. cruzi DNA revealed 188-nucleotide bands, which hybridised to a specific radiolabelled probe and were confirmed by cloning and sequencing. RESULTS Three independent assessments at different time points revealed T. cruzi nuclear DNA footprints in 76% (83/109) of the study population with active infection. In contrast, the ELISA and indirect immunofluorescence assays detected the T. cruzi antibody in 28.4% (31/109) of the study samples. Moreover, the semen from 82.6% (19/23) of subjects people revealed harboured the 188- bp base pair T. cruzi footprint. Interestingly, the ejaculates of nuclear DNA-positive Chagas patient transmitted the T. cruzi upon peritoneal injection or infusion in the vagina of mice, and amastigotes were detected in the skeletal muscle, myocardium, vas deferens, and uterine tube. MAIN CONCLUSIONS T. cruzi infections can be transmitted from females or males to naïve mates through intercourse, and progeny showed discrepancies between the ratios of nuclear DNA footprints and specific antibody that can be explained by the tolerance attained during early embryo growth. Additional studies are needed to develop drugs to eradicate the infections. Additionally, the importance of a vigorous education, information, and communication program to prevent sexually transmitted Chagas disease in humans cannot be underemphasised.

Anesthetic technique for liver transplantation in pigs / Técnica anestésica no transplante de fígado em suínos

Introduction: the interventionists procedures, as in the case of liver surgeries, needs anesthesia toprovide ideal conditions for the patient. Among the animals utilized for experimentation, pigs arehighlighted by their anatomical similarity to humans, being, therefore, a good animal to be studied.Objective: realize anesthesia in surgical procedures on medium-sized animals, mainly in pigs, dueto easy performance and low cost. Method: for this study, fourteen pigs weighing between 8-12 kgwere utilized. Sedation with the application of ketamine was carried out (10 mg/kg) associated withxylazine (1 mg/kg). Then, a catheterization of the internal jugular vein and internal carotid arterywas realized. After this procedure, it was initiated the maintenance with the administration offentanyl 3-5 ?g/kg and ketamine 2-5mg/kg and followed this time with the installation of halothaneand oxygen. Conclusion: the anesthetic technique proposed was easily carried out by trainedprofessionals or students, enabling the realization of liver transplantations as well as other surgeries,demonstrating to be safety for the manipulator and the animal.

Introdução: os procedimentos que têm de intervenção, como no caso das cirurgias de fígado,necessita de anestesia para manter o paciente em condições ideais. Entre os animais utilizados nasexperiências, os porcos são destacados por sua similaridade anatômica para os seres humanos,sendo, portanto, um bom animal a ser estudado. Objetivo: a realização de anestesia emprocedimentos em animais de médio porte, principalmente em suínos por desempenho fácil e debaixo custo. Método: para este estudo, 14 porcos com peso entre 8-12 kg foram utilizados. Sedaçãocom a aplicação de cetamina foi realizada (10 mg / kg) associada com xilazina (1 mg / kg). Emseguida, um cateterismo de veia jugular interna e artéria carótida interna foi realizado. Após esteprocedimento, iniciou-se a manutenção com a administração de fentanil 2-5mg/kg 3-5 mg / kg ecetamina e seguiu-se desta vez com a instalação de halotano e oxigênio. Conclusão: a técnicaanestésica proposta foi facilmente realizada por profissionais treinados ou estudantes, permitindo arealização de transplantes de fígado, assim como outras cirurgias, demonstrando ser de segurançapara o manipulador e o animal.

Síndrome de Loeffler / Loeffler Syndrome

Objetivo: relato de caso de um paciente correlacionando os sintomas pulmonares a parasitose intestinaltambém apresentada pelo paciente. Relato de Caso: paciente de 4 anos com quadro clínico pulmonarassociado a parasitose intestinal e eosinofilia importante. Considerações finais: a infestação parasitáriaconstitui a principal causa de Síndrome de Loeffler (pneumonia eosinofilica) e as manifestações clínicas destetipo de pneumonia são inespecíficas, sendo necessário associar anamnese detalhada aos dados clínicos elaboratoriais para o estabelecimento de um diagnóstico correto e precoce

Objective: case of a patient correlating the pulmonary symptoms the intestinal parasatism alsopresented by the patient. Case report: patient of 4 years old with pulmonary clinical associatedthe intestinal parasatism and important eosinofilia. Final considerations: the parasiticinfestation constitutes the main cause of Syndrome of Loeffler (eosinofilica pneumonia) and theclinical manifestations of this type of pneumonia is inespecíficas, being necessary to associateanamnese detailed to the clinical and laboratoriais data for the establishment of a correct andprecocious diagnosis