RESUMO
Advances in microbiome research are spurring the development of new therapeutics for a variety of diseases, but translational challenges remain.
Assuntos
Microbiota , Medicina de Precisão , Animais , Dieta , Transplante de Microbiota Fecal , Trato Gastrointestinal/efeitos dos fármacos , Humanos , Microbiota/efeitos dos fármacos , Probióticos/farmacologiaRESUMO
Obesity, diabetes, and related manifestations are associated with an enhanced, but poorly understood, risk for mucosal infection and systemic inflammation. Here, we show in mouse models of obesity and diabetes that hyperglycemia drives intestinal barrier permeability, through GLUT2-dependent transcriptional reprogramming of intestinal epithelial cells and alteration of tight and adherence junction integrity. Consequently, hyperglycemia-mediated barrier disruption leads to systemic influx of microbial products and enhanced dissemination of enteric infection. Treatment of hyperglycemia, intestinal epithelial-specific GLUT2 deletion, or inhibition of glucose metabolism restores barrier function and bacterial containment. In humans, systemic influx of intestinal microbiome products correlates with individualized glycemic control, indicated by glycated hemoglobin levels. Together, our results mechanistically link hyperglycemia and intestinal barrier function with systemic infectious and inflammatory consequences of obesity and diabetes.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Infecções por Escherichia coli/fisiopatologia , Hiperglicemia/fisiopatologia , Enteropatias/microbiologia , Enteropatias/fisiopatologia , Animais , Células CACO-2 , Reprogramação Celular , Citrobacter rodentium , Escherichia coli Enteropatogênica , Microbioma Gastrointestinal , Deleção de Genes , Glucose/metabolismo , Glucose/farmacologia , Transportador de Glucose Tipo 2/genética , Humanos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/fisiopatologia , Camundongos , Camundongos Endogâmicos , Obesidade/fisiopatologia , Permeabilidade , Receptores para Leptina/genética , EstreptozocinaRESUMO
OBJECTIVE: Research shows that mindfulness meditation (MM) affects pain perception; however, studies have yet to measure patterns of change over time. We examined effects of MM on perception of experimental heat pain using multiple psychophysical indices, including pattern of change in response to tonic painful stimuli. We also tested the potential moderating role of baseline mindfulness. METHOD: Forty participants were randomly assigned to a brief MM training or control group. We assessed: a) heat pain threshold (HPT), b) temperature which induces pain at a fixed, target intensity level, and c) response pattern over time to tonic heat pain. RESULTS: Compared to control group, the MM group showed increased HPT and more rapid attenuation of pain intensity for tonic pain stimuli. Moderation analyses indicated that baseline mindfulness moderated effects of MM on HPT. CONCLUSIONS: A brief MM intervention appears to affect perception of experimental pain both by increasing pain threshold and accelerating modulation of response. Findings may help elucidate mechanisms of MM for chronic pain.