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The Journal of Immunology
The existence of a neonatal window was first highlighted by epidemiological studies that revealed the particular importance of this early time in life for the susceptibility to immune-mediated diseases in humans. Recently, the first animal studies emerged that present examples of early-life exposure–triggered persisting immune events, allowing a detailed analysis of the factors that define this particular time period. The enteric microbiota and the innate and adaptive immune system represent prime candidates that impact on the pathogenesis of immune-mediated diseases and are known to reach a lasting homeostatic equilibrium following a dynamic priming period after birth. In this review, we outline the postnatal establishment of the microbiota and maturation of the innate and adaptive immune system and discuss examples of early-life exposure–triggered immune-mediated diseases that start to shed light on the critical importance of the early postnatal period for life-long immune homeostasis.
Recent advances in understanding how the mammalian immune system and intestinal microbiota functionally interact have yielded novel insights for human health and disease. Modern technologies to quantitatively measure specific members and functional characteristics of the microbiota in the gastrointestinal tract, along with fundamental and emerging concepts in the field of immunology, have revealed numerous ways in which host-microbiota interactions proceed beneficially, neutrally, or detrimentally for mammalian hosts. It is clear that the gut microbiota has a strong influence on the shape and quality of the immune system; correspondingly, the immune system guides the composition and localization of the microbiota. In the following review, we examine the evidence that these interactions encompass homeostasis and inflammation in the intestine and, in certain cases, extraintestinal tissues. Lastly, we discuss translational therapies stemming from research on host-microbiota interactions that could be used for the treatment of chronic inflammatory diseases.
The mammalian gastrointestinal tract and associated mucosal immune system harbor a large repertoire of metabolites of prokaryotic and eukaryotic origin that play important roles in eukaryotic development and physiology. These often bioactive small molecules originate from nutrition- and environmental-related sources, or are endogenously produced and modulated by the host and its microbiota. A complex network of interactions exists between the intestinal mucosal immune system and the microbiota. This intimate cross-talk may be driven by metabolite secretion and signaling, and features profound influences on host immunity and physiology, including the endocrine, metabolic, and nervous system function in health and disease. Alterations in microbiome-associated metabolite levels and activity are implicated in the pathogenesis of a growing number of illnesses. In this review we discuss the origin and influence of microbiome-modulated metabolites, with an emphasis on immune cell development and function. We further highlight the emerging data potentially implicating metabolite misbalance with host-microbiome–associated disease.