The pulmonary microbiome: challenges of a new paradigm / Microbioma pulmonar: desafios de um novo paradigma

ABSTRACT The study of the human microbiome-and, more recently, that of the respiratory system-by means of sophisticated molecular biology techniques, has revealed the immense diversity of microbial colonization in humans, in human health, and in various diseases. Apparently, contrary to what has been believed, there can be nonpathogenic colonization of the lungs by microorganisms such as bacteria, fungi, and viruses. Although this physiological lung microbiome presents low colony density, it presents high diversity. However, some pathological conditions lead to a loss of that diversity, with increasing concentrations of some bacterial genera, to the detriment of others. Although we possess qualitative knowledge of the bacteria present in the lungs in different states of health or disease, that knowledge has advanced to an understanding of the interaction of this microbiota with the local and systemic immune systems, through which it modulates the immune response. Given this intrinsic relationship between the microbiota and the lungs, studies have put forth new concepts about the pathophysiological mechanisms of homeostasis in the respiratory system and the potential dysbiosis in some diseases, such as cystic fibrosis, COPD, asthma, and interstitial lung disease. This departure from the paradigm regarding knowledge of the lung microbiota has made it imperative to improve understanding of the role of the microbiome, in order to identify possible therapeutic targets and to develop innovative clinical approaches. Through this new leap of knowledge, the results of preliminary studies could translate to benefits for our patients.

RESUMO O estudo do microbioma humano - e, mais recentemente, o do sistema respiratório - através de sofisticadas técnicas de biologia molecular, desvendou a imensa diversidade de colonização microbiana nos seres humanos, sejam saudáveis, sejam portadores de diferentes doenças. Aparentemente, ao contrário do que se acreditava, existe uma colonização não patogênica dos pulmões por microrganismos, como bactérias, fungos e vírus. Esse microbioma pulmonar fisiológico apresenta uma densidade baixa de colônias, porém uma elevada diversidade; por outro lado, alguns estados patológicos levam a uma perda dessa diversidade, com aumento da concentração de alguns gêneros bacterianos em detrimento de outros. Ainda, além do conhecimento qualitativo das bactérias presentes no pulmão em diversos estados de saúde ou de doença, o conhecimento avança para o entendimento da interação que essa microbiota tem com o sistema imune local e sistêmico, modulando a resposta imunológica. Compreendendo essa intrínseca relação entre a microbiota e os pulmões, estudos apresentam novos conceitos sobre os mecanismos fisiopatogênicos da homeostase do sistema respiratório e a possível disbiose em estado de algumas doenças, como fibrose cística, DPOC, asma e doenças intersticiais. Essa quebra de paradigma do conhecimento da microbiota presente nos pulmões fez com que se torne premente entender melhor o papel do microbioma para identificar possíveis alvos terapêuticos e abordagens clínicas inovadoras. Através desse novo salto de conhecimento é que os resultados dos estudos preliminares poderão ser traduzidos em benefícios aos nossos pacientes.

Microbiota intestinal: sua importância e função / Intestinal microbiota: its importance and function

O corpo humano alberga mais microrganismos do que as próprias células constituintes do corpo. O trato gastrointestinal é o local de maior densidade e diversidade de comunidades bacterianas, e a microbiota intestinal exerce enorme impacto sobre a função e a saúde do sistema digestivo e sobre a saúde do organismo humano como um todo. Evidências indicam que a dieta pode determinar a quantidade e o tipo de microrganismos da microbiota gastrointestinal, mesmo quando há enterótipos estabelecidos por padrões dietéticos de longo prazo. A microbiota intestinal também constitui fator ambiental capaz de aumentar o rendimento energético a partir da dieta, e de regular o metabolismo periférico, podendo resultar em ganho de peso. Nesta revisão abordaremos o desenvolvimento, a composição e a função da microbiota intestinal, oferecento uma visão geral de como suas anormalidades podem relacionar-se com enfermidade, incluindo doenças intestinais

The human body hosts more microbial cells than our own body cells. The gastrointestinal tract is the site where bacterial communities reach the greatest density and diversity within the body, and the intestinal microbiota plays a crucial role on the function and health of the digestive system, and the health of the whole human organism. Recent evidence indicates that the diet can affect the gut microbiome composition even when there are enterotypes established by long-term dietary patterns. The intestinal microbiota also constitutes an environmental factor capable of increasing the energy yield from diet, regulating peripheral metabolism and increasing body weight. In this review, we discuss the development, composition, and function of the intestinal microbiota presenting an overview of how its derangements may relate to diseases in general, including intestinal diseases

Coevolutionary networks: a novel approach to understanding the relationships of humans with the infectious agents

Human organism is interpenetrated by the world of microorganisms, from the conception until the death. This interpenetration involves different levels of interactions between the partners including trophic exchanges, bi-directional cell signaling and gene activation, besides genetic and epigenetic phenomena, and tends towards mutual adaptation and coevolution. Since these processes are critical for the survival of individuals and species, they rely on the existence of a complex organization of adaptive systems aiming at two apparently conflicting purposes: the maintenance of the internal coherence of each partner, and a mutually advantageous coexistence and progressive adaptation between them. Humans possess three adaptive systems: the nervous, the endocrine and the immune system, each internally organized into subsystems functionally connected by intraconnections, to maintain the internal coherence of the system. The three adaptive systems aim at the maintenance of the internal coherence of the organism and are functionally linked by interconnections, in such way that what happens to one is immediately sensed by the others. The different communities of infectious agents that live within the organism are also organized into functional networks. The members of each community are linked by intraconnections, represented by the mutual trophic, metabolic and other influences, while the different infectious communities affect each other through interconnections. Furthermore, by means of its adaptive systems, the organism influences and is influenced by the microbial communities through the existence of transconnections. It is proposed that these highly complex and dynamic networks, involving gene exchange and epigenetic phenomena, represent major coevolutionary forces for humans and microorganisms