Translational research : the journal of laboratory and clinical medicine
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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.
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The microbial population residing within the human gut represents one of the most densely populated microbial niche in the human body with growing evidence showing it playing a key role in the regulation of behavior and brain function. The bidirectional communication between the gut microbiota and the brain, the microbiota-gut-brain axis, occurs through various pathways including the vagus nerve, the immune system, neuroendocrine pathways, and bacteria-derived metabolites. This axis has been shown to influence neurotransmission and the behavior that are often associated with neuropsychiatric conditions. ⋯ Numerous factors have been highlighted to influence gut microbiota composition, including genetics, health status, mode of birth, and environment. However, it is diet composition and nutritional status that has repeatedly been shown to be one of the most critical modifiable factors regulating the gut microbiota at different time points across the lifespan and under various health conditions. Thus the microbiota is poised to play a key role in nutritional interventions for maintaining brain health.
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Inflammatory bowel diseases (IBDs) are chronic diseases of unclear etiology that affect over 1 million individuals in the United States and over 2.5 million people in Europe. However, they are also expanding globally, affecting populations in Asia, South America, and the Middle East as they become more industrialized. These diseases are believed to arise from the convergence of genetic, environmental, and microbial factors that trigger aberrant immune and tissue responses, resulting in intestinal inflammation. ⋯ However, determining and understanding the functional consequences of gut dysbiosis and altered host-microbiota interactions in IBD remain a challenge due to the limits of current experimental models and difficulty in establishing causal links in human-based investigations. Continued development of new methodologies and improvements in clinical study design are needed to better understand the interplay of genetic, microbial, and immunological factors in IBD. This knowledge can then be applied clinically to improve therapeutic strategies and outcomes for IBD.
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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.
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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.