Interacción del microbioma intestinal y el hueso / Interaction between the intestinal microbiome and bone

El "microbioma" no solo está constituido por los microbios, sino por todos los componen-tes que viven en el mismo hábitat conforman-do un nicho ecológico. Es decir, está conformado por los microorganismos (bacterias, hongos, protozoos, etc.), todo el espectro de moléculas producidas por ellos tales como sus componentes estructurales (ácidos nucleicos, proteínas, lípidos y glúcidos), meta-bolitos, toxinas, etc., y las moléculas producidas por el huésped. El microbioma intestinal (MI) ha emergido como un factor que tiene un gran efecto sobre la cantidad, calidad y fuerza del hueso. Las investigaciones revelan que la homeostasis ósea está ligada al micro-bioma saludable, mientras que la disbiosis (alteración en la biodiversidad microbiana) puede exacerbar la actividad osteoclástica y promover la osteoporosis. Los mecanismos potenciales involucrados en la interacción del microbioma intestinal y el hueso son la influencia del metabolismo del huésped, el mantenimiento de la integridad intestinal y regulación de la absorción de nutrientes, la regulación del eje intestino-sistema inmune y la modulación del sistema endocrino. Es decir que hay múltiples vías por las cuales el MI influye sobre el hueso, pero estos y otros mecanismos deben profundizarse más aún. También es necesario que se identifiquen y caractericen mejor los microorganismos que están asociados a las enfermedades óseas. El conocimiento de estos aspectos podría ser útil para el desarrollo de herramientas terapéuticas basadas en el MI que puedan mejorar la eficacia de los distintos tratamientos existentes. (AU)

The microbiome is not only constituted by microbes, but by all the components that live in the same habitat forming an ecological niche. It is conformed by the microorganisms ( bacteria, fungi, protozoa, etc), the entire spectrum of molecules produced by them (nucleic acids, proteins, lipid and carbohydrates, metabolites, toxins, etc) and the molecules produced by the host. The intestinal microbiome (IM) has emerged as a factor with great effects on the quantity, quality and strength of bone. The investigations reveal that bone homeostasis is linked to the healthy microbiome, while the dysbiosis (alteration in the microbial biodiversity) can exacerbate the osteoclastic activity and promote osteoporosis. The potential mechanisms involved in the interaction between IM and bone are the influence of the host metabolism, the maintenance of the intestinal integrity and regulation of the nutrient absorption, the regulation of the intestine/ immune system axis and the modulation of the endocrine system. That is, there are multiple ways through which IM influences on bone, but these and other mechanisms need to be further studied. It is also necessary to identify and characterize the microorganisms associated with the bone diseases. Knowledge of these aspects could be useful to develop therapeutical tools based on the IM that could improve the efficacy of the current treatments. (AU)

Gut microbiota in Mexican patients with common variable immunodeficiency

Introduction: Common variable immunodeficiency (CVID) is the main symptomatic primary immunodeficiency and is associated with complex immune disorders. Gut microbiota interacts closely with the immune system, and intestinal dysbiosis is related to multiple diseases. Objective: To describe for the first time the composition of gut microbiota in Mexican patients with CVID. Methods: Fecal samples from five patients with CVID were collected and massive sequencing of the V3-V4 region of 16S rRNA gene was carried out using illumina technology. Results: Bacterial relative abundance was observed at all taxonomic levels. Firmicutes, Actinobacteria and Verrucomicrobia were the predominant phyla. The Clostridia class and the Clostridial order were the most common in their respective taxon; the Ruminococcaceae family predominated. A total of 166 genera were reported, with the most abundant being Faecalibacterium. Five species were identified, but only Bifidobacterium longum was present in all patients. Conclusions: Unlike healthy subjects' gut microbiota, where Firmicutes and Bacteroidetes predominate, the microbiota of the patients with CVID considered in this study was abundant in Firmicutes, Actinobacteria and Verrucomicrobia. The low presence of Bacteroidetes and high abundance of Firmicutes might indicate the existence of intestinal dysbiosis in these patients.

Evolução da colonização da microbiota fecal de recém-nascidos prematuros submetidos à colostroterapia / Evolution of fecal microbiota colonization in preterm infants submitted to colostrum therapy

A amamentação tem um papel importante no desenvolvimento neonatal e no estabelecimento da microbiota intestinal. Neste contexto, a administração orofaríngea de colostro, ou colostroterapia, torna-se uma prática importante para o desenvolvimento do recém-nascido prematuro, auxiliando na maturação do trato gastrintestinal, na introdução precoce do leite materno e pode ser capaz de proteger o bebê contra bactérias patogênicas. Desta maneira, o objetivo do presente estudo foi avaliar o estabelecimento da microbiota intestinal em recém-nascidos prematuros submetidos à colostroterapia. O estudo contou com a inclusão de 33 recém-nascidos prematuros internados na unidade de terapia intensiva neonatal do Hospital Maternidade Leonor Mendes de Barros, em São Paulo. Os recém-nascidos foram divididos em quatro grupos, de acordo com o regime de colostroterapia e dieta, a saber: colostroterapia exclusiva com colostro cru (CCE, n=7), colostroterapia exclusiva com colostro pasteurizado (CPE, n=9), colostroterapia com colostro pasteurizado e dieta prevalente de colostro pasteurizado (CPC, n=10) e colostroterapia com colostro pasteurizado e dieta prevalente de leite humano pasteurizado (CPP, n=7). Foram coletadas amostras de fezes semanalmente durante os primeiros 22 dias de vida do bebê, e a microbiota intestinal foi caracterizada por sequenciamento da região V4 do gene 16S rRNA e análises de PCR em tempo real. Entre os grupos de CCE e CPE nota-se que existe diferença na comunidade bacteriana através das análises de abundância relativa da microbiota. Porém, a abundância de gêneros potencialmente patogênicos está aumentada nos grupos CPC e CPP. A presença de bifidobactérias e aumento contínuo ao longo dos primeiros dias de vida no grupo CPE e CPP, é um resultado que pode ser utilizado para reforçar o uso do leite pasteurizado na ausência do leite fresco, mostrando que o mesmo pode favorecer a prevalência de gêneros benéficos para a microbiota intestinal. Neste estudo, além de compararmos a modulação do colostro cru e pasteurizado na microbiota intestinal do bebê a partir da colostroterapia exclusiva, pudemos mostrar que o colostro pasteurizado desempenha um papel diferente que o leite humano pasteurizado na microbiota intestinal

Breastfeeding plays an important role in neonatal development and establishment of the intestinal microbiota. In this context, oropharyngeal administration of colostrum, or colostrum therapy, becomes an important practice for the development of preterm infant, assisting in maturation of the gastrointestinal tract, early introduction of breast milk and may be able to protect the baby against pathogenic bacteria. Thus, the aim of the present study was to evaluate the establishment of the intestinal microbiota in preterm infants submitted to colostrum therapy. The study included 33 preterm infants admitted to the neonatal intensive care unit of the Hospital Maternidade Leonor Mendes de Barros, in São Paulo. The newborns were divided into four groups according to the colostrum therapy and diet regimen: exclusive colostrum therapy with raw colostrum (CCE, n = 7), exclusive colostrum therapy with pasteurized colostrum (CPE, n = 9), colostrum therapy with pasteurized colostrum and pasteurized colostrum diet (CPC, n = 10) and colostrum therapy with pasteurized colostrum and pasteurized human milk diet (CPP, n = 7). Stool samples were collected weekly during the first 22 days of the baby's life, and the intestinal microbiota was characterized by sequencing the V4 region of the 16S rRNA gene and realtime PCR analysis. Between the CCE and CPE groups, there is a difference in the bacterial community through the microbiota relative abundance analysis. However, the abundance of potentially pathogenic genera is increased in the CPC and CPP groups. The presence of bifidobacteria and continuous increase throughout the first days of life in the CPE and CPP group is a result that can be used to reinforce the use of pasteurized milk in the absence of fresh milk, showing that it may favor the prevalence of beneficial bacteria genera to the intestinal microbiota. In this study, in addition to comparing the modulation of raw and pasteurized colostrum in the baby's intestinal microbiota from exclusive colostrum therapy, we were able to show that pasteurized colostrum plays a different role than pasteurized human milk in the intestinal microbiota of preterm infant

Suplementação de minerais por meio da castanha-do-brasil pode modular a microbiota intestinal de indivíduos saudáveis / Mineral supplementation through Brazil nuts can modulate the intestinal microbiota of healthy individuals

A castanha-do-brasil é um alimento de alta complexidade nutricional, devido ao alto teor de selênio, micronutriente com ação antioxidante e anti-inflamatória, e de outros importantes componentes, como fibras, ácidos graxos insaturados, compostos fenólicos e diversos minerais, como zinco, cobre e magnésio. Essa noz é amplamente consumida pela população brasileira e mundial e seus efeitos à saúde devem ser compreendidos em todas as vertentes. Até o momento, não eram conhecidos os efeitos da ingestão dessa castanha na constituição de bactérias intestinais, cuja relevância vem sendo exponencialmente comprovada na literatura nacional e mundial devido sua participação em importantes processos no contexto saúde e doença. Nesse sentido, o objetivo deste trabalho foi avaliar a composição da microbiota intestinal e o perfil de minerais (metaloma) no organismo após a ingestão de castanha-do-brasil (Bertholletia excelsa H.B.K.). Este estudo prospectivo foi composto por 97 indivíduos sem doenças crônicas não transmissíveis, de ambos os gêneros, com idade média de 28,7 ± 8,5 anos. Os participantes foram avaliados antes e após a suplementação de uma unidade de castanha-do-brasil (~370 µg de selênio) por dia, durante 60 dias, quanto ao status de minerais (plasma, eritrócitos e fezes), atividade da enzima glutationa peroxidase (GPX), concentração de selenoproteína P (SEPP), avaliação da ingestão alimentar (recordatório alimentar de 24 horas) e caracterização do microbioma intestinal. Os dados brutos do microbioma foram analisados por meio do software Quantitative Insight into Microbial Ecology (v1.9.0) e a estatística foi realizada utilizando o pacote R (v1.1.463). Nossos resultados indicaram que a castanha-do-brasil melhorou significativamente o status de selênio da população, de acordo com o aumento expressivo das concentrações no organismo (plasma, eritrócitos e fezes) e de seus marcadores funcionais (selenoproteína P e atividade da GPX) (p<0,0001). A intervenção também alterou a concentração de outros elementos químicos (cobalto, arsênio, manganês, bário, chumbo, cobre, zinco, alumínio, ferro e magnésio) no plasma, eritrócitos e fezes (p<0,001). Esse estudo foi inédito em reportar os efeitos da intervenção com castanha-do-brasil na comunidade bacteriana intestinal. Apesar da composição global do microbioma intestinal não ter sido alterada após a ingestão de castanha, a abundância de gêneros importantes à saúde humana, como Faecalibacterium, Bilophila e Bulleidia, foi aumentada. Além disso, o perfil metalômico nas fezes também influenciou a constituição e distribuição de grupos bacterianos, após o consumo da noz. Observamos também correlações significativas entre os minerais avaliados e as bactérias produtoras de ácidos graxos de cadeia curta, como Prevotella, Ruminococcus, Oscillospira e Coprococcus. Portanto, pode-se concluir que a intervenção com castanha-dobrasil beneficiou a constituição e distribuição da microbiota intestinal e evidenciou a influência do perfil metalômico nas fezes sobre grupos bacterianos importantes à saúde humana

Brazil nut is a food of high nutritional complexity, due to the high selenium content, micronutrient with antioxidant and anti-inflammatory action, and other important components such as fibers, unsaturated fatty acids, phenolic compounds and various minerals, like zinc, copper and magnesium. This nut is widely consumed by the Brazilian and world population and its health effects must be understood in all aspects. To date, the effects of ingestion of this nut on the constitution of intestinal bacteria were unknown, whose relevance has been exponentially proven in the national and world literature due to its participation in important processes of health and disease. In this sense, the objective of this work was to evaluate the composition of the intestinal microbiota and the mineral profile (metalloma) in the organism after ingestion of Brazil nuts (Bertholletia excels H.B.K.). This prospective study consisted of 97 subjects without chronic noncommunicable diseases of both genders, with a mean age of 28.7 ± 8.5 years. Participants were evaluated before and after supplementation with one unit of Brazil nut (~ 370 µg selenium) per day for 60 days for mineral status (plasma, erythrocytes and feces), glutathione peroxidase (GPX), selenoprotein P (SEPP) concentration, assessment of food intake (24-hour dietary recall) and characterization of the intestinal microbiome. Raw microbiome data were analyzed using Quantitative Insight into Microbial Ecology software (v1.9.0) and statistics were performed using the R package (v1.1.463). Our results indicated that Brazil nuts significantly improved the selenium status of the population, according to the significant increase in concentrations in the body (plasma, erythrocytes and feces) and its functional markers (selenoprotein P and GPX activity) (p <0.0001). The intervention also altered the concentration of other chemical elements (cobalt, arsenic, manganese, barium, lead, copper, zinc, aluminum, iron and magnesium) in plasma, erythrocytes and feces (p <0.001). This study was unprecedented in reporting the effects of Brazil nut intervention on the intestinal bacterial community. Although the overall composition of the intestinal microbiome did not change after ingestion of nuts, the abundance of genera important to human health, such as Faecalibacterium, Bilophila and Bulleidia, was increased. In addition, the metallomic profile in faeces also influenced the constitution and distribution of bacterial groups after nut consumption. We also observed significant correlations between the evaluated minerals and short chain fatty acid producing bacteria, such as Prevotella, Ruminococcus, Oscillospira and Coprococcus. Therefore, it can be concluded that the intervention with Brazil nuts benefited the constitution and distribution of the intestinal microbiota and evidenced the influence of the fecal metallomic profile on bacterial groups important to human health

Rol de la microbiota gastrointestinal en la regulación de la respuesta inmune / The role of gut microbiota in the regulation of the immune response

The gastrointestinal tract hosts around 10(14) bacterial microorganisms, in a constantly growing density from the stomach to the distal colon. This microbiota is composed by more than 500 species of bacteria, which are quickly acquired after birth, fairly stable during the host’s life, and essential for human homeostasis. These bacteria have important functions, such as stimulating the immune system, protecting the host from invading bacteria and viruses, and improving digestion, especially of complex carbohydrates. Also, the gut microbiota interacts directly with the immune system. However, the interaction of the intestinal epithelium and its microbiota with the immune system has yet to be fully understood. Secretory immunoglobulin A, produced by the plasma cells in Peyer’s patches and in the lamina propria, maintains non-invasive commensal bacteria and neutralize invasive pathogens. Dendritic cells migrate from the lamina propria of the secondary lymphoid organs to regulate gut immunity. They also have a key role maintaining luminal IgA and inducing the growth of regulatory T cells. Dendritic cells supervise the gut microenvironment too, keeping an immunological equilibrium and tolerance. The importance of the gut microbiota in regulating the immune system lies mostly in the homeostasis-or positive equilibrium. Thus, many diseases are a consequence of poor interactions or a loss of this equilibrium.