Gut Microbiota Dysbiosis Induced by a High-Fat Diet Increases Susceptibility to Atrial Fibrillation

BackgroundObesity is a significant risk factor for atrial fibrillation (AF), and the gut microbiota is closely related to obesity-induced diseases. However, whether the gut microbiota is involved in regulating obesity-induced AF has not been studied. This study investigated whether gut microbiota dysbiosis affects obesity-related AF.MethodsFecal microbes derived from normal diet (ND)-fed and high-fat diet (HD)-fed mice were transplanted into those fed normally. Morphologic, biochemical, functional, histologic, electrophysiological studies, molecular analysis, 16S rRNA gene amplicon sequencing, and RNA-sequencing were performed.ResultsTransplantation of the HD gut microbes in ND-maintained (THD) mice led to a significant increase in the susceptibility to AF. Gut microbiota analysis showed a significant increase in Desulfovibrionaceae, which generated metabolic endotoxemia in THD mice. Transplantation with HD microbes also resulted in significantly increased levels of circulating lipopolysaccharide (LPS), significant disruption in the histologic architecture of the intestinal tissue, and significantly increased proinflammatory cytokines in the left atrium, indicating that atrial inflammation likely contributed to AF susceptibility. RNA-sequencing showed that the THD group had enhanced activation of ferroptosis and TLR4/NF-κB/NLRP3 inflammasome signalling pathway. Inhibiting the ferroptosis or NLRP3 inflammasome signalling pathway significantly improved atrial fibrosis and reduced susceptibility to obesity-related gut dysbiosis-induced AF.ConclusionsThis study provides evidence showing an original causal role of gut microbiota dysbiosis in the pathogenesis of obesity-related AF, which showed elevated LPS and dysregulation of atrial pathologic remodelling by activating ferroptosis and the TLR4/NF-κB/NLRP3 inflammasome signalling pathway.     

Airway Microbiota and the Implications of Dysbiosis in Asthma

The mucosal surfaces of the human body are typically colonized by polymicrobial communities seeded in infancy and are continuously shaped by environmental exposures. These communities interact with the mucosal immune system to maintain homeostasis in health, but perturbations in their composition and function are associated with lower airway diseases, including asthma, a developmental and heterogeneous chronic disease with various degrees and types of airway inflammation. This review will summarize recent studies examining airway microbiota dysbioses associated with asthma and their relationship with the pathophysiology of this disease.     

Gut Microbiota and the Pathogenesis of Insulin Resistance

Several reviews recently explored how the gut microbiota was able to control host energy metabolism, and thereby the development of adiposity. In this review, we focused on the state of the art that supports a link between the gut microbiota composition and activity, and the management of glycemia associated with overweight and diabetes. Several microbial-derived compounds are related to disturbances of glucose homeostasis including the gram-negative–derived lipopolysaccharides. Some nutrients with prebiotic properties, which escape the digestion in the upper part of the gut, modify the composition of the gut microbiota in favor of bacteria that could play a beneficial role on glucose homeostasis, namely by modulating the endocrine function of the gut, and by reinforcing the gut barrier. Adequate intervention studies in diabetic patients are required to assess the relevance of those experimental data for human health.     

Heart Block,Ptosis, and Diagnostic Funduscopic Examination: Problems of the Heart Seen Through the Eyes

Mitochondrial diseases are complex and rare clinical entities that can sometimes be diagnosed by their constellation of simple clinical signs. We describe a 24-year-old insulin-dependent diabetic women who was diagnosed with complete heart block and required permanent pacemaker implantation. Astute physical examination revealed opthalmoparesis, ptosis, and pigmentary retinopathy consistent with a diagnosis of Kearns-Sayre syndrome. When a young patient presents with complete heart block, a neurologic examination including funduscopy can identify Kearns-Sayre syndrome, which has far-reaching consequence for the index patient and offspring.     

Influences of the Gut Microbiota on DNA Methylation and Histone Modification

The gut microbiota is a vast ensemble of microorganisms inhabiting the mammalian gastrointestinal tract that can impact physiologic and pathologic processes. However, our understanding of the underlying mechanism for the dynamic interaction between host and gut microbiota is still in its infancy. The highly evolved epigenetic modifications allow hosts to reprogram the genome in response to environmental stimuli, which may play a key role in triggering multiple human diseases. In spite of increasing studies in gut microbiota and epigenetic modifications, the correlation between them has not been well elaborated. Here, we review current knowledge of gut microbiota impacts on epigenetic modifications, the major evidence of which centers on DNA methylation and histone modification of the immune system.     

The Role of the Manipulation of the Gut Microbiota in Obesity

The manipulation of the gut microbiota by diet, antibiotics, or probiotics could promote, prevent, or reverse the development of specific diseases, including obesity. A link has been proposed between obesity and the growth promoters (probiotics and antibiotics) that have been used in animals for more than 40 years to induce weight gain. Several species of the Lactobacillus genus that are frequently used as probiotics for human consumption merit particular attention because they are increased in the gut microbiota under high-fat diets, are more abundant in obese humans, and are selected by growth-promoter antibiotics; moreover, the administration of these bacteria in experimental models is linked to the development of obesity. However, other species or strains of the same genus are associated with an antiobesity effect. Newborns and infants are a particularly susceptible population in which the administration of antibiotics or probiotics could be related to the development of obesity in adulthood.     

Diabetic Cardiovascular Disease: Getting to the Heart of the Matter

Diabetes is a major risk factor for heart disease, and heart disease is responsible for substantial morbidity and mortality among people living with diabetes. The diabetic metabolic milieu predisposes to aggressive obstructive coronary artery disease that causes heart attacks, heart failure, and death. Furthermore, diabetes can be associated with heart failure, independent of underlying coronary artery disease, hypertension, or valve abnormalities. The pathogenesis of the vascular and myocardial complications of diabetes is, as yet, incompletely understood. Although a number of medical and surgical approaches can improve outcomes in diabetic patients with cardiovascular disease, much remains to be learned in order to optimize approaches to these critical complications.