RESUMO
Diabetes Mellitus (DM) is an inflammatory clinical entity with different mechanisms involved in its physiopathology. Among these, the dysfunction of the gut microbiota stands out. Currently, it is understood that lipid products derived from the gut microbiota are capable of interacting with cells from the immune system and have an immunomodulatory effect. In the presence of dysbiosis, the concentration of lipopolysaccharides (LPS) increases, favoring damage to the intestinal barrier. Furthermore, a pro-inflammatory environment prevails, and a state of insulin resistance and hyperglycemia is present. Conversely, during eubiosis, the production of short-chain fatty acids (SCFA) is fundamental for the maintenance of the integrity of the intestinal barrier as well as for immunogenic tolerance and appetite/satiety perception, leading to a protective effect. Additionally, it has been demonstrated that alterations or dysregulation of the gut microbiota can be reversed by modifying the eating habits of the patients or with the administration of prebiotics, probiotics, and symbiotics. Similarly, different studies have demonstrated that drugs like Metformin are capable of modifying the composition of the gut microbiota, promoting changes in the biosynthesis of LPS, and the metabolism of SCFA.
Assuntos
Diabetes Mellitus/microbiologia , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/fisiologia , Sistema Imunitário/microbiologia , Lipopolissacarídeos/biossíntese , Disbiose/imunologia , Humanos , Hiperglicemia/microbiologia , Tolerância Imunológica , Inflamação , Resistência à Insulina/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Prebióticos/administração & dosagem , Probióticos/administração & dosagem , Simbióticos/administração & dosagemRESUMO
PURPOSE OF REVIEW: We review how an altered microbiome in early life impacts on immune, metabolic, and neurological development, focusing on some of the most widespread diseases related to each of these processes, namely atopic disease, obesity, and autism. RECENT FINDINGS: The early development of the microbial communities that inhabit the human body is currently challenged by factors that range from reduced exposure to microbes, antibiotic use, and poor dietary choices to widespread environmental pollution. Recent work has highlighted some of the long-term consequences that early alterations in the establishment of these microbiotas can have for different aspects of human development and health. The long-term consequences of early microbiome alterations for human development and health are only beginning to be understood and will require in-depth investigation in the years to come. A solid understanding of how present day environmental conditions alter microbiome development, and of how an altered microbiome in early life impacts on life-long health, should inform both public health policies and the development of dietary and medical strategies to counteract early microbiota imbalances.
Assuntos
Microbioma Gastrointestinal/fisiologia , Sistema Imunitário/microbiologia , Microbiota , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Poluição do Ar/efeitos adversos , Feminino , Trato Gastrointestinal/microbiologia , Humanos , Intestinos/microbiologia , Doenças Metabólicas/metabolismo , GravidezRESUMO
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.
Assuntos
Humanos , Disbiose/imunologia , Microbiota/fisiologia , Sistema Imunitário/microbiologia , Pulmão/microbiologia , Pneumopatias/microbiologiaRESUMO
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.
Assuntos
Disbiose/imunologia , Sistema Imunitário/microbiologia , Pneumopatias/microbiologia , Pulmão/microbiologia , Microbiota/fisiologia , HumanosRESUMO
Introduction: Compared to bovine formula (BF), breast milk (BM) has unique properties. In the newborn intestine, there is a homeostatic balance between the counterparts of the immune system, which allows a physiological inflammation, modulated by the gut microbiota. Many studies have attempted to understand the effect of BF vs. BM, and the changes in the gut microbiota, but few also focus on intestinal inflammation. Methods: We conducted a cohort study of newborn infants during their first 3 months. In stool samples taken at 1 and 3 months (timepoints T1 and T3), we quantified calprotectin, IL-8 and α1-antitrypsin by ELISA and we evaluated the expression of IL8 and IL1ß genes by RT-qPCR. To determine the microbiota composition, the 16S rRNA gene was amplified and sequenced using 454 pyrosequencing. Sequences were clustered into operational taxonomic units (OTUs). Results: In total 15 BM and 10 BF infants were enrolled. In the BM group, we found calprotectin and α1-antitrypsin levels were significantly elevated at T3 compared to T1; no differences were found between T1 and T3 in the BF group. A comparison between the BM and BF groups showed that calprotectin levels at T1 were lower in the BM than the BF group; this difference was not observed at T3. For IL-8 levels, we found no differences between groups. A gene expression analysis of the IL8 and IL1ß genes showed that infants from the BF group at T1 have a significantly increased expression of these markers compared to the BM group. Gut microbiota analyses revealed that the phylum Bacteroidetes was higher in BM than BF, whereas Firmicutes were higher in BF. A redundancy analysis and ANOVA showed BM has a community structure statistically different to BF at T1 but not at T3. Compared to BF, BM at T1 showed a higher representation of Enterococcus, Streptococcus, Enterobacter, Lactococcus, and Propionibacterium. Conclusions: We found a basal state of inflammation in the infants' intestine based on inflammation markers. One month after birth, infants receiving BF exhibited higher levels of inflammation compared to BM.
Assuntos
Fórmulas Infantis/microbiologia , Inflamação/microbiologia , Intestinos/microbiologia , Microbiota/imunologia , Leite Humano/microbiologia , Bacteroidetes/genética , Bacteroidetes/imunologia , Chile , Estudos de Coortes , Firmicutes/genética , Firmicutes/imunologia , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/microbiologia , Lactente , Recém-Nascido , Inflamação/imunologia , Inflamação/patologia , Intestinos/imunologia , Intestinos/patologia , Complexo Antígeno L1 Leucocitário/análise , Microbiota/genética , alfa 1-Antitripsina/análiseRESUMO
Under physiologic conditions, the human gut microbiota performs several activities essential to the body health. In contrast, their imbalances exacerbate some actions which can promote a cascade of metabolic abnormalities, and vice versa. Numerous diseases, including chronic kidney disease, are associated with gut microbiota imbalance, and among several strategies to re-establish gut symbiosis, prebiotics seem to represent an effective nonpharmacological approach. Prebiotics fermentation by gut microbiota produce short-chain fatty acids, which improve the gut barrier integrity and function, and modulate the glucose and lipid metabolism as well as the inflammatory response and immune system. Therefore, this literature review intends to discuss the beneficial effects of prebiotics in human health through short-chain fatty acids production, with a particular interest on chronic kidney disease.
Assuntos
Ácidos Graxos/metabolismo , Microbioma Gastrointestinal , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Prebióticos , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/microbiologia , Glucose/metabolismo , Humanos , Sistema Imunitário/microbiologia , Metabolismo dos Lipídeos , Simbiose/fisiologiaRESUMO
Type 1 diabetes (T1D) is the second most frequent autoimmune disease in childhood. The long-term micro- and macro-vascular complications of diabetes are associated with the leading causes of disability and even mortality in young adults. Understanding the T1D etiology will allow the design of preventive strategies to avoid or delay the T1D onset and to help to maintain control after developing. T1D development involves genetic and environmental factors, such as birth delivery mode, use of antibiotics, and diet. Gut microbiota could be the link between environmental factors, the development of autoimmunity, and T1D. In this review, we will focus on the dietary factor and its relationship with the gut microbiota in the complex process involved in autoimmunity and T1D. The molecular mechanisms involved will also be addressed, and finally, evidence-based strategies for potential primary and secondary prevention of T1D will be discussed.
Assuntos
Doenças Autoimunes/imunologia , Diabetes Mellitus Tipo 1/imunologia , Dieta , Microbioma Gastrointestinal , Sistema Imunitário/microbiologia , Animais , Doenças Autoimunes/microbiologia , Diabetes Mellitus Tipo 1/microbiologia , Diabetes Mellitus Tipo 1/prevenção & controle , Modelos Animais de Doenças , Trato Gastrointestinal/microbiologia , Humanos , Sistema Imunitário/imunologiaRESUMO
The commensal microbiota is in constant interaction with the immune system, teaching immune cells to respond to antigens. Studies in mice have demonstrated that manipulation of the intestinal microbiota alters host immune cell homeostasis. Additionally, metagenomic-sequencing analysis has revealed alterations in intestinal microbiota in patients suffering from inflammatory bowel disease, asthma, and obesity. Perturbations in the microbiota composition result in a deficient immune response and impaired tolerance to commensal microorganisms. Due to altered microbiota composition which is associated to some inflammatory diseases, several strategies, such as the administration of probiotics, diet, and antibiotic usage, have been utilized to prevent or ameliorate chronic inflammatory diseases. The purpose of this review is to present and discuss recent evidence showing that the gut microbiota controls immune system function and onset, development, and resolution of some common inflammatory diseases.
Assuntos
Trato Gastrointestinal/imunologia , Sistema Imunitário/imunologia , Doenças Inflamatórias Intestinais/imunologia , Microbiota/imunologia , Doença Crônica , Trato Gastrointestinal/microbiologia , Humanos , Sistema Imunitário/microbiologia , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/terapia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Modelos ImunológicosRESUMO
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
Assuntos
Intestinos/microbiologia , Trato Gastrointestinal/microbiologia , Fenômenos Fisiológicos Bacterianos , Bactérias/isolamento & purificação , Dieta , Metabolismo Energético , Homeostase , Imunidade Inata , Prebióticos , Probióticos , Simbióticos , Sistema Imunitário/microbiologiaRESUMO
We are not alone. The indigenous microbiota colonizes exposed surfaces and aids their hosts in several physiological activities. The transition between a non-colonized to a colonized state is associated with modification on the pattern of host inflammatory responsiveness. Therefore, innate immunity adapts to the colonized state of the host, suggesting that there is an acquired component in innate immune responses.