Translational research : the journal of laboratory and clinical medicine
-
Among the many areas being revolutionized by the recent introduction of culture-independent microbial identification techniques is investigation of the relationship between close contact with large animals, antibiotics, breast feeding, mode of birth, and other exposures during infancy as related to a reduced risk of asthma and allergic disease. These exposures were originally clustered under the "Hygiene Hypothesis" which has evolved into the "Microbiota Hypothesis". This review begins by summarizing epidemiologic studies suggesting that the common feature of these allergy risk-related exposures is their influence on the founding and early development of a child's gut microbiota. ⋯ Finally, selected mouse and human studies are presented which begin to corroborate the protective exposures identified in epidemiologic studies by elucidating mechanisms through which microbes can alter immune development and function. These microbially driven immune alterations demonstrate that microbial exposures in many cases could alter the risk of subsequent allergic disease and asthma. Hopefully, a better understanding of how microbes influence allergic disease will lead to safe and effective methods for reducing the prevalence of all forms of allergic disease.
-
The gut microbiota has both direct and indirect effects on drug and xenobiotic metabolisms, and this can have consequences for both efficacy and toxicity. Indeed, microbiome-driven drug metabolism is essential for the activation of certain prodrugs, for example, azo drugs such as prontosil and neoprontosil resulting in the release of sulfanilamide. ⋯ In addition to direct effects, the gut microbiota can affect drug metabolism and toxicity indirectly via, for example, the modulation of host drug metabolism and disposition and competition of bacterial-derived metabolites for xenobiotic metabolism pathways. Also, of course, the therapeutic drugs themselves can have effects, both intended and unwanted, which can impact the health and composition of the gut microbiota with unforeseen consequences.
-
Obesity increases the risks of many cancers. One important mechanism behind this association is the obesity-associated proinflammatory state. Although the composition of the intestinal microbiome undoubtedly can contribute to the proinflammatory state, perhaps the most important aspect of host-microbiome interactions is host exposure to components of intestinal bacteria that stimulate inflammatory reactions. ⋯ Biomarkers of bacterial exposures that have been measured in blood include LPS-binding protein, sCD14, fatty acids characteristic of intestinal bacteria, and immunoglobulins specific for bacterial LPS and flagellin. The optimal strategies to reduce these proinflammatory exposures, whether by altering diet composition, avoiding a positive energy balance, or reducing adipose stores, likely differ in each individual. Biomarkers that assess systemic bacterial exposures therefore should be useful to (1) optimize and personalize preventive approaches for individuals and groups with specific characteristics and to (2) gain insight into the possible mechanisms involved with different preventive approaches.
-
More than 100 trillion microbial cells that reside in the human gut heavily influence nutrition, metabolism, and immune function of the host. Gut dysbiosis, seen commonly in patients with chronic kidney disease (CKD), results from qualitative and quantitative changes in host microbiome profile and disruption of gut barrier function. ⋯ We present a discussion of dysbiosis, various uremic toxins produced from dysbiotic gut microbiome, and their roles in CKD progression and complications. We also review the gut microbiome in renal transplant, highlighting the role of commensal microbes in alteration of immune responses to transplantation, and conclude with therapeutic interventions that aim to restore intestinal dysbiosis.
-
Skin scar formation is characterized by excessive synthesis and aberrant deposition of collagens during wound healing. MicroRNAs are endogenous gene regulators critically involved in diverse biological events including skin scar formation and hold considerable promise as therapeutic targets. However, the detailed molecular mechanisms responsible for collagen production during skin wound repair and scar formation remain incompletely known. ⋯ Importantly, local delivery of miR-29b lentiviral particles inhibited HSP47 expression and collagen biosynthesis as well as suppressed angiogenesis, thus reducing scar formation in an excisional wound splinting model. Collectively, our data reveal that miR-29b can reduce collagen biosynthesis during skin wound healing likely via post-transcriptional inhibition of HSP47 expression. These findings also suggest that therapeutic targeting of miR-29b/HSP47 might be a viable alternative strategy to prevent or reduce scar formation.