The microbiota is an important factor in the development of the immune response. The interaction between the gastrointestinal tract and resident microbiota is well balanced in healthy individuals, ...but its breakdown can lead to intestinal and extraintestinal disease. We review current knowledge about the mechanisms that regulate the interaction between the immune system and the microbiota, focusing on the role of resident intestinal bacteria in the development of immune responses. We also discuss mechanisms that prevent immune responses against resident bacteria, and how the indigenous bacteria stimulate the immune system to protect against commensal pathobionts and exogenous pathogens. Unraveling the complex interactions between resident intestinal bacteria and the immune system could improve our understanding of disease pathogenesis and lead to new therapeutic approaches.
Abstract
An increasing body of literature reveals that host–microbe networks are well coordinated and impact human health and disease. Recently, it has become evident that an abnormal alteration in ...bacterial configuration in the oral cavity, namely oral dysbiosis, caused by periodontal inflammation, is associated with various distant inflammatory diseases, including inflammatory bowel disease. However, the extent to which the relationships between oral and distant disorders are merely an association or are causally triggered by oral microorganisms remains debated. In this mini-review, we highlight mechanisms in inter-related organ system diseases, particularly the one between oral and gut inflammation. Further, we discuss clinical perspectives and propose a novel concept of a multi-hit hypothesis in the pathogenesis of gut inflammation, on the basis of our updated knowledge of shared microbiological and immunological pathways between the oral and gut mucosae.
Graphical Abstract
Graphical Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract. Although the precise etiology of IBD is largely unknown, it is widely thought that diet contributes ...to the development of IBD. Diet shapes the composition of the gut microbiota, which plays critical roles in intestinal homeostasis. In contrast, intestinal inflammation induces gut dysbiosis and may affect the use of dietary nutrients by host cells and the gut microbiota. The interaction of diet and the gut microbiota is perturbed in patients with IBD. Herein, we review the current knowledge of diet and gut microbiota interaction in intestinal homeostasis. We also discuss alterations of diet and gut microbiota interaction that influence the outcome and the nutritional treatment of IBD. Understanding the complex relationships between diet and the gut microbiota provides crucial insight into the pathogenesis of IBD and advances the development of new therapeutic approaches.
While conventional approaches for inflammatory bowel diseases mainly focus on suppressing hyperactive immune responses, it remains unclear how to address disrupted intestinal barriers, dysbiosis of ...the gut commensal microbiota and dysregulated mucosal immune responses in inflammatory bowel diseases. Moreover, immunosuppressive agents can cause off-target systemic side effects and complications. Here, we report the development of hyaluronic acid-bilirubin nanomedicine (HABN) that accumulates in inflamed colonic epithelium and restores the epithelium barriers in a murine model of acute colitis. Surprisingly, HABN also modulates the gut microbiota, increasing the overall richness and diversity and markedly augmenting the abundance of Akkermansia muciniphila and Clostridium XIVα, which are microorganisms with crucial roles in gut homeostasis. Importantly, HABN associated with pro-inflammatory macrophages, regulated innate immune responses and exerted potent therapeutic efficacy against colitis. Our work sheds light on the impact of nanotherapeutics on gut homeostasis, microbiome and innate immune responses for the treatment of inflammatory diseases.
The mammalian intestine is colonized by trillions of microorganisms, most of which are bacteria that have co-evolved with the host in a symbiotic relationship. The collection of microbial populations ...that reside on and in the host is commonly referred to as the microbiota. A principal function of the microbiota is to protect the intestine against colonization by exogenous pathogens and potentially harmful indigenous microorganisms via several mechanisms, which include direct competition for limited nutrients and the modulation of host immune responses. Conversely, pathogens have developed strategies to promote their replication in the presence of competing microbiota. Breakdown of the normal microbial community increases the risk of pathogen infection, the overgrowth of harmful pathobionts and inflammatory disease. Understanding the interaction of the microbiota with pathogens and the host might provide new insights into the pathogenesis of disease, as well as novel avenues for preventing and treating intestinal and systemic disorders.
Mammals are colonized by large numbers of microorganisms, including trillions of bacteria, most of which live in the intestinal tract. These indigenous microorganisms that inhabit the body of humans ...and animals are referred collectively to as the microbiota. Accumulating evidence indicates that the microbiota regulates the development and/or function of different types of immune cells in the intestine. For example, the microbiota drives homeostatic, pathogenic, and regulatory T cell immune responses that contribute to tissue homeostasis, but also can promote disease. The gut microbes also facilitate IgA responses, which in turn regulate the composition and function of the gut microbiota. Thus, the reciprocal regulation of the gut microbiota and the host immune system may influence the balance between homeostasis and disease in the intestine.
A dense resident microbial community in the gut, referred as the commensal microbiota, coevolved with the host and is essential for many host physiological processes that include enhancement of the ...intestinal epithelial barrier, development of the immune system and acquisition of nutrients. A major function of the microbiota is protection against colonization by pathogens and overgrowth of indigenous pathobionts that can result from the disruption of the healthy microbial community. The mechanisms that regulate the ability of the microbiota to restrain pathogen growth are complex and include competitive metabolic interactions, localization to intestinal niches and induction of host immune responses. Pathogens, in turn, have evolved strategies to escape from commensal-mediated resistance to colonization. Thus, the interplay between commensals and pathogens or indigenous pathobionts is critical for controlling infection and disease. Understanding pathogen-commensal interactions may lead to new therapeutic approaches to treating infectious diseases.
A vast community of commensal microorganisms, commonly referred to as the gut microbiota, colonizes the gastrointestinal tract (GI). The involvement of the gut microbiota in the maintenance of the ...gut ecosystem is two-fold: it educates host immune cells and protects the host from pathogens. However, when healthy microbial composition and function are disrupted (dysbiosis), the dysbiotic gut microbiota can trigger the initiation and development of various GI diseases, including inflammatory bowel disease (IBD). IBD, primarily includes ulcerative colitis (UC) and Crohn's disease (CD), is a major global public health problem affecting over 1 million patients in the United States alone. Accumulating evidence suggests that various environmental and genetic factors contribute to the pathogenesis of IBD. In particular, the gut microbiota is a key factor associated with the triggering and presentation of disease. Gut dysbiosis in patients with IBD is defined as a reduction of beneficial commensal bacteria and an enrichment of potentially harmful commensal bacteria (pathobionts). However, as of now it is largely unknown whether gut dysbiosis is a cause or a consequence of IBD. Recent technological advances have made it possible to address this question and investigate the functional impact of dysbiotic microbiota on IBD. In this review, we will discuss the recent advances in the field, focusing on host-microbial cross-talk in IBD.
Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disease of the gastrointestinal tract. Although the precise etiology of IBD remains incompletely understood, accumulating ...evidence suggests that various environmental factors, including dietary nutrients, contribute to its pathogenesis. Dietary nutrients are known to have an impact on host physiology and diseases. The interactions between dietary nutrients and intestinal immunity are complex. Dietary nutrients directly regulate the immuno-modulatory function of gut-resident immune cells. Likewise, dietary nutrients shape the composition of the gut microbiota. Therefore, a well-balanced diet is crucial for good health. In contrast, the relationships among dietary nutrients, host immunity and/or the gut microbiota may be perturbed in the context of IBD. Genetic predispositions and gut dysbiosis may affect the utilization of dietary nutrients. Moreover, the metabolism of nutrients in host cells and the gut microbiota may be altered by intestinal inflammation, thereby increasing or decreasing the demand for certain nutrients necessary for the maintenance of immune and microbial homeostasis. Herein, we review the current knowledge of the role dietary nutrients play in the development and the treatment of IBD, focusing on the interplay among dietary nutrients, the gut microbiota and host immune cells. We also discuss alterations in the nutritional metabolism of the gut microbiota and host cells in IBD that can influence the outcome of nutritional intervention. A better understanding of the diet-host-microbiota interactions may lead to new therapeutic approaches for the treatment of IBD.
Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a ...gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota, and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome, and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics.
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•Characterized synthetic bacterial communities enable functional insights in vivo•Low-fiber diet promotes expansion and activity of colonic mucus-degrading bacteria•Purified prebiotic fibers do not alleviate degradation of the mucus layer•Fiber-deprived gut microbiota promotes aggressive colitis by an enteric pathogen
Regular consumption of dietary fiber helps prevent erosion of the intestinal mucus barrier by the gut microbiome, blunting pathogen infection and reducing the incidence of colitis.
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