Human diseases are increasingly linked with an altered or “dysbiotic” gut microbiota, but whether such changes are causal, consequential, or bystanders to disease is, for the most part, unresolved. ...Human microbiota-associated (HMA) rodents have become a cornerstone of microbiome science for addressing causal relationships between altered microbiomes and host pathology. In a systematic review, we found that 95% of published studies (36/38) on HMA rodents reported a transfer of pathological phenotypes to recipient animals, and many extrapolated the findings to make causal inferences to human diseases. We posit that this exceedingly high rate of inter-species transferable pathologies is implausible and overstates the role of the gut microbiome in human disease. We advocate for a more rigorous and critical approach for inferring causality to avoid false concepts and prevent unrealistic expectations that may undermine the credibility of microbiome science and delay its translation.
Walter and colleagues argue that human-microbiota-associated rodent experiments are generally overinterpreted and misused. In this Perspective, they provide a framework for improving the rigor of these gold-standard experiments to sort out truly causal microbiome-disease relationships.
Gut microbiota in health and disease Sekirov, Inna; Russell, Shannon L; Antunes, L Caetano M ...
Physiological reviews
90, Številka:
3
Journal Article
Recenzirano
Gut microbiota is an assortment of microorganisms inhabiting the length and width of the mammalian gastrointestinal tract. The composition of this microbial community is host specific, evolving ...throughout an individual's lifetime and susceptible to both exogenous and endogenous modifications. Recent renewed interest in the structure and function of this "organ" has illuminated its central position in health and disease. The microbiota is intimately involved in numerous aspects of normal host physiology, from nutritional status to behavior and stress response. Additionally, they can be a central or a contributing cause of many diseases, affecting both near and far organ systems. The overall balance in the composition of the gut microbial community, as well as the presence or absence of key species capable of effecting specific responses, is important in ensuring homeostasis or lack thereof at the intestinal mucosa and beyond. The mechanisms through which microbiota exerts its beneficial or detrimental influences remain largely undefined, but include elaboration of signaling molecules and recognition of bacterial epitopes by both intestinal epithelial and mucosal immune cells. The advances in modeling and analysis of gut microbiota will further our knowledge of their role in health and disease, allowing customization of existing and future therapeutic and prophylactic modalities.
Asthma is a common chronic respiratory disease affecting more than 300 million people worldwide. Clinical features of asthma and its immunological and molecular etiology vary significantly among ...patients. An understanding of the complexities of asthma has evolved to the point where precision medicine approaches, including microbiome analysis, are being increasingly recognized as an important part of disease management. Lung and gut microbiota play several important roles in the development, regulation, and maintenance of healthy immune responses. Dysbiosis and subsequent dysregulation of microbiota-related immunological processes affect the onset of the disease, its clinical characteristics, and responses to treatment. Bacteria and viruses are the most extensively studied microorganisms relating to asthma pathogenesis, but other microbes, including fungi and even archaea, can potently influence airway inflammation. This review focuses on recently discovered connections between lung and gut microbiota, including bacteria, fungi, viruses, and archaea, and their influence on asthma.
Dysregulation of microbiota-related immunological processes affects the onset of asthma, its clinical characteristics, and responses to treatment. Finlay et al. review connections between gut and lungs microbiota and its influence on allergic airway inflammation. This review covers not only the most well-known populations of microbes in the context of asthma—bacteria—but also discusses viruses, fungi, and archaea.
Escherichia coli is a remarkable and diverse organism. This normally harmless commensal needs only to acquire a combination of mobile genetic elements to become a highly adapted pathogen capable of ...causing a range of diseases, from gastroenteritis to extraintestinal infections of the urinary tract, bloodstream and central nervous system. The worldwide burden of these diseases is staggering, with hundreds of millions of people affected annually. Eight E. coli pathovars have been well characterized, and each uses a large arsenal of virulence factors to subvert host cellular functions to potentiate its virulence. In this Review, we focus on the recent advances in our understanding of the different pathogenic mechanisms that are used by various E. coli pathovars and how they cause disease in humans.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IgA mediates microbial homeostasis at the intestinal mucosa. Within the gut, IgA acts in a context-dependent manner to both prevent and promote bacterial colonization and to influence bacterial gene ...expression, thus providing exquisite control of the microbiota. IgA-microbiota interactions are highly diverse across individuals and populations, yet the factors driving this variation remain poorly understood. In this Review, we summarize evidence for the host, bacterial and environmental factors that influence IgA-microbiota interactions. Recent advances have helped to clarify the antigenic specificity and immune selection of intestinal IgA and have highlighted the importance of microbial glycan recognition. Furthermore, emerging evidence suggests that diet and nutrition play an important role in shaping IgA recognition of the microbiota. IgA-microbiota interactions are disrupted during both overnutrition and undernutrition and may be altered dynamically in response to diet, with potential implications for host health. We situate this research in the context of outstanding questions and future directions in order to better understand the fascinating paradigm of IgA-microbiota homeostasis.
The assembly of microbial communities within the gastrointestinal tract during early life plays a critical role in immune, endocrine, metabolic, and other host developmental pathways. Environmental ...insults during this period, such as food insecurity and infections, can disrupt this optimal microbial succession, which may contribute to lifelong and intergenerational deficits in growth and development. Here, we review the human microbiome in the first 1000 days – referring to the period from conception to 2 years of age – and using a developmental model, we examine the role of early microbial succession in growth and development. We propose that an ‘undernourished’ microbiome is intergenerational, thereby perpetuating growth impairments into successive generations. We also identify and discuss the intertwining host–microbe–environment interactions occurring prenatally and during early infancy, which may impair the trajectories of healthy growth and development, and explore their potential as novel microbial targets for intervention.
Undernutrition is influenced by infections, subclinical pathogen carriage and metabolic impact of ‘dysbiotic’ commensal gut microbial communities (gut microbiota) in infants during the first 1000 days.
Delayed or immature assembly of the gut microbiota underlies severe acute malnutrition in children.
The gut microbiota affects the somatotropic axis through regulation of IGF-1 and growth hormone production, thereby affecting growth.
There is emerging knowledge of the influence of prenatal microbial communities on fetal and postnatal growth.
The gut microbiota plays an influential role in inflammation and enteropathy, which may be linked to growth faltering.
The first 1000 days provides a window of opportunity for modulating the microbiota through interventions such as diet, antibiotics, probiotics, prebiotics, or fecal microbiota transplantation to promote healthy growth and development.
Mucus production by goblet cells of the large intestine serves as a crucial antimicrobial protective mechanism at the interface between the eukaryotic and prokaryotic cells of the mammalian ...intestinal ecosystem. However, the regulatory pathways involved in goblet cell-induced mucus secretion remain largely unknown. Here, we demonstrate that the NLRP6 inflammasome, a recently described regulator of colonic microbiota composition and biogeographical distribution, is a critical orchestrator of goblet cell mucin granule exocytosis. NLRP6 deficiency leads to defective autophagy in goblet cells and abrogated mucus secretion into the large intestinal lumen. Consequently, NLRP6 inflammasome-deficient mice are unable to clear enteric pathogens from the mucosal surface, rendering them highly susceptible to persistent infection. This study identifies an innate immune regulatory pathway governing goblet cell mucus secretion, linking nonhematopoietic inflammasome signaling to autophagy and highlighting the goblet cell as a critical innate immune player in the control of intestinal host-microbial mutualism.
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•The NLRP6 inflammasome is highly expressed in intestinal goblet cells•NLRP6 inflammasome regulates goblet cell mucus secretion•NLRP6 regulation of goblet cells is mediated through induction of autophagy•Altered NLRP6 signaling induces impaired mucus layer and susceptibility to infection
Intestinal goblet cells secrete mucus and antimicrobial peptides to ward off pathogens, with the NLRP6 inflammasome, an immune sensor, being central to regulating mucus granule secretion.
Human microbiota-associated (HMA) mice have been used extensively in gut microbiome research. Here we discuss ecological and evolutionary aspects of the mammalian-gut microbiome interrelationship ...that confound the application of HMA mice, and propose experimental designs that increase the likelihood for obtaining meaningful findings.
Human microbiota-associated (HMA) mice have been used extensively in gut microbiome research. Here we discuss ecological and evolutionary aspects of the mammalian-gut microbiome interrelationship that confound the application of HMA mice, and propose experimental designs that increase the likelihood for obtaining meaningful findings.
There is currently much interest in defining how the microbiota shapes immune responses in the context of cancer. Various studies in both mice and humans have associated particular commensal species ...with better (or worse) outcomes in different cancer types and following treatment with cancer immunotherapies. However, the mechanisms involved remain ill-defined and even controversial. In this Viewpoint, Nature Reviews Immunology has invited six eminent scientists in the field to share their thoughts on the key questions and challenges for the field.
Almost half the cells and 1% of the unique genes found in our bodies are human, the rest are from microbes, predominantly bacteria, archaea, fungi, and viruses. These microorganisms collectively form ...the human microbiota, with most colonizing the gut. Recent technological advances, open access data libraries, and application of high‐throughput sequencing have allowed these microbes to be identified and their contribution to neurological health to be examined. Emerging evidence links perturbations in the gut microbiota to neurological disease, including disease risk, activity, and progression. This review provides an overview of the recent advances in microbiome research in relation to neuro(auto)immune and neurodegenerative conditions affecting humans, such as multiple sclerosis, neuromyelitis optica spectrum disorders, Parkinson disease, Alzheimer disease, Huntington disease, and amyotrophic lateral sclerosis. Study design and terminology used in this rapidly evolving, highly multidisciplinary field are summarized to empower and engage the neurology community in this “newly discovered organ.” Ann Neurol 2017;81:369–382
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