Featured ArticlesVolume 5 | No. 9 | Sept. 2016
|The changing microbial landscape of Western society: Diet, dwellings and discordanceIn an anthropologic approach, Suzanne Devkota and Josiane Broussard suggest that post-industrialization changes to diet in conjunction with physical environments contribute to the rise in chronic inflammatory and metabolic diseases. Their evolutionary take on (gut-) microbial selection due to Western diet and our self-inflicted restriction to mostly indoor-habitats and life-style choices create physical barriers for bacterial exposure. This review offers a general introduction on the subject with a lens on microbiome-host co-evolution and human health and diseases.|
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Background: The last 50–100 years has been marked by a sharp rise in so-called “Western-diseases” in those countries that have experienced major industrial advances and shifts towards urbanized living. These diseases include obesity, type 2 diabetes, inflammatory bowel diseases, and food allergies in which chronic dysregulation of metabolic and/or immune processes appear to be involved, and are likely a byproduct of new environmental influences on our ancient genome. What we now appreciate is that this genome consists of both human and co-evolved microbial genes of the trillions of microbes residing in our body. Together, host–microbe interactions may be determined by the changing diets and behaviors of the Western lifestyle, influencing the etiopathogenesis of “new-age” diseases.
Scope of review: This review takes an anthropological approach to the potential interplay of the host and its gut microbiome in the post-industrialization rise in chronic inflammatory and metabolic diseases. The discussion highlights both the changes in diet and the physical environment that have co-occurred with these diseases and the latest evidence demonstrating the role of host–microbe interactions in understanding biological responses to the changing environment.
Major conclusions: Technological advances that have led to changes in agriculture and engineering have altered our eating and living behaviors in ways never before possible in human history. These changes also have altered the bacterial communities within the human body in ways that are seemingly linked with the rise of many intestinal and systemic metabolic and inflammatory diseases. Insights into the mechanisms of this reciprocal exchange between the environment and the human gut microbiome may offer potential to attenuate the chronic health conditions that derail quality of life. This article is part of a special issue on microbiota.[Hide abstract]
|How gut microbes talk to organs: The role of endocrine and nervous routesPatrice Cani and Claude Knauf review an extensive body of literature on the endocrine, enteric, and central signalling routes affected by gut microbiota. The authors emphasize new metabolites and molecules that mediate the bidirectional exchange of information and highlight underappreciated elements of inter-organ communication that bear potential for future therapeutic exploration.|
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Background: Changes in gut microbiota composition and activity have been associated with different metabolic disorders, including obesity, diabetes, and cardiometabolic disorders. Recent evidence suggests that different organs are directly under the influence of bacterial metabolites that may directly or indirectly regulate physiological and pathological processes.
Scope of review: We reviewed seminal as well as recent papers showing that gut microbes influence energy, glucose and lipid homeostasis by controlling different metabolic routes such as endocrine, enteric and central nervous system. These dialogues are discussed in the context of obesity and diabetes but also for brain pathologies and neurodegenerative disorders.
Major conclusions: The recent advances in gut microbiota investigation as well as the discovery of specific metabolites interacting with host cells has led to the identification of novel inter-organ communication during metabolic disturbances. This suggests that gut microbes may be viewed as “novel” future therapeutic partners.[Hide abstract]
|Microbial regulation of GLP-1 and L-cell biologyFredrik Bäckhed and Thomas Greiner discuss the differential sensing of microbial metabolites along the intestinal tract. Their review outlines morphological, functional, and molecular features in the enteroendocrine cells that line distinct parts of the gut. These differences are mirrored by distinct microbial species, highlighting the spatial complexity and functional adaptation in host-microbiota interactions.|
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Background: The gut microbiota is associated with several of metabolic diseases, including obesity and type 2 diabetes and affects host physiology through distinct mechanisms. The microbiota produces a vast array of metabolites that signal to host cells in the intestine as well as in more distal organs.
Scope of review: Enteroendocrine cells acts as ‘chemo sensors’ of the intestinal milieu by expressing a large number of receptors, which respond to different metabolites and nutrients, and signal to host by a wide variety of hormones. However, enteroendocrine cells differ along the length of the gut in terms of hormones expressed and receptor repertoire. Also, the microbial ecology and dietary substrates differ along the length of the gut, providing further evidence for unique functions of specific subpopulations among enteroendocrine cells. Here we will review how the gut microbiota interacts with L-cells in the small and large intestine and the resulting effects on the host.
Major conclusions: Microbial metabolites can be sensed differently by specific subpopulations of enteroendocrine cells. Furthermore, hormones such as GLP-1 can have different functions when originating from the small intestine or colon. This article is part of a special issue on microbiota.[Hide abstract]
|Causality of small and large intestinal microbiota in weight regulation and insulin resistanceMax Nieuwdorp et al. focus on the role of gut microbiota on host weight-regulation and the onset of insulin resistance. Notably, altered microbial composition (dysbiosis) has been linked to changes in gut permeability, dietary energy harvest, and satiety signals. These findings support personalized therapies such as fecal microbiota transfer or bariatric surgery and could make these procedures more successful in the future.|
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Objective: The twin pandemics of obesity and Type 2 diabetes (T2D) are a global challenge for health care systems. Changes in the environment, behavior, diet, and lifestyle during the last decades are considered the major causes. A Western diet, which is rich in saturated fat and simple sugars, may lead to changes in gut microbial composition and physiology, which have recently been linked to the development of metabolic diseases.
Methods: We will discuss evidence that demonstrates the influence of the small and large intestinal microbiota on weight regulation and the development of insulin resistance, based on literature search.
Results: Altered large intestinal microbial composition may promote obesity by increasing energy harvest through specialized gut microbes. In both large and small intestine, microbial alterations may increase gut permeability that facilitates the translocation of whole bacteria or endotoxic bacterial components into metabolic active tissues. Moreover, changed microbial communities may affect the production of satiety-inducing signals. Finally, bacterial metabolic products, such as short chain fatty acids (SCFAs) and their relative ratios, may be causal in disturbed immune and metabolic signaling, notably in the small intestine where the surface is large. The function of these organs (adipose tissue, brain, liver, muscle, pancreas) may be disturbed by the induction of low-grade inflammation, contributing to insulin resistance.
Conclusions: Interventions aimed to restoring gut microbial homeostasis, such as ingestion of specific fibers or therapeutic microbes, are promising strategies to reduce insulin resistance and the related metabolic abnormalities in obesity, metabolic syndrome, and type 2 diabetes. This article is part of a special issue on microbiota.[Hide abstract]
|Gut microbiota and immune crosstalk in metabolic diseaseThe impact of gut microbiota on the host’s immune system takes center stage in Remy Burcelin’s review. Starting from a ‘holobiont’ (the host in the context of its microbiome) perspective, the immune system is recognized as the first line of defense in protecting the host against damaging dysbiotic microbes. Conversely, the immune system should tolerate beneficial changes in the intestinal microbiota population. Hence, gut microbes could serve as informative biomarkers for the host’s immune status while vaccination strategies could help to protect from the onset of metabolically devastating dysbiosis.|
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Background: Gut microbiota is considered as a major regulator of metabolic disease. This reconciles the notion of metabolic inflammation and the epidemic development of the disease. In addition to evidence showing that a specific gut microbiota characterizes patients with obesity, type 2 diabetes, and hepatic steatosis, the mechanisms causal to the disease could be related to the translocation of microbiota from the gut to the tissues, inducing inflammation. The mechanisms regulating such a process are based on the crosstalk between the gut microbiota and the host immune system. The hologenome theory of evolution supports this concept and implies that therapeutic strategies aiming to control glycemia should take into account both the gut microbiota and the host immune system.
Scope of review: This review discusses the latest evidence regarding the bidirectional impact of the gut microbiota on host immune system crosstalk for the control of metabolic disease, hyperglycemia, and obesity. To avoid redundancies with the literature, we will focus our attention on the intestinal immune system, identifying evidence for the generation of novel therapeutic strategies, which could be based on the control of the translocation of gut bacteria to tissues. Such novel strategies should hamper the role played by gut microbiota dysbiosis on the development of metabolic inflammation.
Major conclusions: Recent evidence in rodents allows us to conclude that an impaired intestinal immune system characterizes and could be causal in the development of metabolic disease. The fine understanding of the molecular mechanisms should allow for the development of a first line of treatment for metabolic disease and its co-morbidities.[Hide abstract]
|Non-alcoholic fatty liver and the gut microbiotaEmphasizing an emerging global health burden, Eran Elinav et al. take a close look at gut microbiota as the major environmental contributor to the onset and development of non-alcoholic fatty liver disease (NAFLD). The review discusses multiple mechanisms of how microbiota may affect the gut-liver signaling axis in this very poorly understood condition. Summarizing new insights into NAFLD-pathologies, it also offers promising new directions for microbiota-based therapeutic interventions.|
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Non-alcoholic fatty liver (NAFLD) is a common, multi-factorial, and poorly understood liver disease whose incidence is globally rising. NAFLD is generally asymptomatic and associated with other manifestations of the metabolic syndrome. Yet, up to 25% of NAFLD patients develop a progressive inflammatory liver disease termed non-alcoholic steatohepatitis (NASH) that may progress towards cirrhosis, hepatocellular carcinoma, and the need for liver transplantation.
Scope of review: Herein, we discuss the associations, mechanisms, and clinical implications of the microbiome's contribution to NAFLD and NASH. Understanding these contributions to the development of fatty liver pathogenesis and its clinical course may serve as a basis for development of therapeutic microbiome-targeting approaches for treatment and prevention of NAFLD and NASH.
Major conclusions: Intestinal host–microbiome interactions play diverse roles in the pathogenesis and progression of NAFLD and NASH. Elucidation of the mechanisms driving these microbial effects on the pathogenesis of NAFLD and NASH may enable to identify new diagnostic and therapeutic targets of these common metabolic liver diseases.[Hide abstract]
|Interactions between host genetics and gut microbiome in diabetes and metabolic syndromeDescribing their Interaction Model, Siegfried Ussar, Shiho Fujisaka, and C. Ronald Kahn highlight the importance of appropriate animal models in analyzing the complex interaction between the gut microbiome and host genetics. The authors also discuss how diet leads to differences in weight gain, levels of insulin resistance, and metabolic outcomes depending on the animal model used.|
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Background: Diabetes, obesity, and the metabolic syndrome are multifactorial diseases dependent on a complex interaction of host genetics, diet, and other environmental factors. Increasing evidence places gut microbiota as important modulators of the crosstalk between diet and development of obesity and metabolic dysfunction. In addition, host genetics can have important impact on the composition and function of gut microbiota. Indeed, depending on the genetic background of the host, diet and other environmental factors may produce different changes in gut microbiota, have different impacts on host metabolism, and create different interactions between the microbiome and the host.
Scope of review: In this review, we highlight how appropriate animal models can help dissect the complex interaction of host genetics with the gut microbiome and how diet can lead to different degrees of weight gain, levels of insulin resistance, and metabolic outcomes, such as diabetes, in different individuals. We also discuss the challenges of identifying specific disease-associated microbiota and the limitations of simple metrics, such as phylogenetic diversity or the ratio of Firmicutes to Bacteroidetes.
Major conclusions: Understanding these complex interactions will help in the development of novel treatments for microbiome-related metabolic diseases. This article is part of a special issue on microbiota.[Hide abstract]