Microbiota Mediate Enhanced Exercise Capacity Induced by Exercise Training.

PURPOSE: We investigated the effects of gut microbes, and the mechanisms mediating the enhanced exercise performance induced by exercise training, i.e., skeletal muscle blood flow, and mitochondrial biogenesis and oxidative function in male mice. METHODS: All mice received a graded exercise test before (PRE) and after exercise training via forced treadmill running at 60% to 70% of maximal running capacity 5 d·wk -1 for 5 wk (POST). To examine the role of the gut microbes, the graded exercise was repeated after 7 d of access to antibiotic (ABX)-treated water, used to eliminate gut microbes. Peripheral blood flow, mitochondrial oxidative capacity, and markers of mitochondrial biogenesis were collected at each time point. RESULTS: Exercise training led to increases of 60% ± 13% in maximal running distance and 63% ± 11% work to exhaustion ( P < 0.001). These increases were abolished after ABX ( P < 0.001). Exercise training increased hindlimb blood flow and markers of mitochondrial biogenesis and oxidative function, including AMP-activated protein kinase, sirtuin-1, PGC-1α citrate synthase, complex IV, and nitric oxide, all of which were also abolished by ABX treatment. CONCLUSIONS: Our results support the concept that gut microbiota mediate enhanced exercise capacity after exercise training and the mechanisms responsible, i.e., hindlimb blood flow, mitochondrial biogenesis, and metabolic profile. Finally, results of this study emphasize the need to fully examine the impact of prescribing ABX to athletes during their training regimens and how this may affect their performance.

The Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome by Downregulating miRNA that Target Inflammatory Pathways.

Acute respiratory distress syndrome (ARDS) is defined as a type of respiratory failure that is caused by a variety of insults such as pneumonia, sepsis, trauma and certain viral infections. In this study, we investigated the effect of an endocannabinoid, anandamide (AEA), on ARDS induced in the mouse by Staphylococcus Enterotoxin B (SEB). Administration of a single intranasal dose of SEB in mice and treated with exogenous AEA at a dose of 40 mg/kg body weight led to the amelioration of ARDS in mice. Clinically, plethysmography results indicated that there was an improvement in lung function after AEA treatment accompanied by a decrease of inflammatory cell infiltrate. There was also a significant decrease in pro-inflammatory cytokines IL-2, TNF-α, and IFN-γ, and immune cells including CD4+ T cells, CD8+ T cells, Vß8+ T cells, and NK+ T cells in the lungs. Concurrently, an increase in anti-inflammatory phenotypes such as CD11b + Gr1+ Myeloid-derived Suppressor Cells (MDSCs), CD4 + FOXP3 + Tregs, and CD4+IL10 + cells was observed in the lungs. Microarray data showed that AEA treatment in ARDS mice significantly altered numerous miRNA including downregulation of miRNA-23a-3p, which caused an upregulation of arginase (ARG1), which encodes for arginase, a marker for MDSCs, as well as TGF-ß2, which induces Tregs. AEA also caused down-regulation of miRNA-34a-5p which led to induction of FoxP3, a master regulator of Tregs. Transfection of T cells using miRNA-23a-3p or miRNA-34a-5p mimics and inhibitors confirmed that these miRNAs targeted ARG1, TGFß2 and FoxP3. In conclusion, the data obtained from this study suggests that endocannabinoids such as AEA can attenuate ARDS induced by SEB by suppressing inflammation through down-regulation of key miRNA that regulate immunosuppressive pathways involving the induction of MDSCs and Tregs.

Regulation of Intestinal Stem Cell Stemness by the Aryl Hydrocarbon Receptor and Its Ligands.

Maintenance of intestinal homeostasis requires the integration of immunological and molecular processes together with environmental, diet, metabolic and microbial cues. Key to this homeostasis is the proper functioning of epithelial cells originating from intestinal stem cells (ISCs). While local factors and numerous molecular pathways govern the ISC niche, the conduit through which these processes work in concordance is the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, whose role in immunoregulation is critical at barrier surfaces. In this review, we discuss how AhR signaling is emerging as one of the critical regulators of molecular pathways involved in epithelial cell renewal. In addition, we examine the putative contribution of specific AhR ligands to ISC stemness and epithelial cell fate.

Role of Dietary Lipids in Modulating Inflammation through the Gut Microbiota.

Inflammation and its resolution is a tenuous balance that is under constant contest. Though several regulatory mechanisms are employed to maintain homeostasis, disruptions in the regulation of inflammation can lead to detrimental effects for the host. Of note, the gut and microbial dysbiosis are implicated in the pathology of systemic chronic low-grade inflammation which has been linked to several metabolic diseases. What remains to be described is the extent to which dietary fat and concomitant changes in the gut microbiota contribute to, or arise from, the onset of metabolic disorders. The present review will highlight the role of microorganisms in host energy regulation and several mechanisms that contribute to inflammatory pathways. This review will also discuss the immunomodulatory effects of the endocannabinoid system and its link with the gut microbiota. Finally, a brief discussion arguing for improved taxonomic resolution (at the species and strain level) is needed to deepen our current knowledge of the microbiota and host inflammatory state.

Microbes and mental health: A review.

There is a growing emphasis on the relationship between the microorganisms inhabiting the gut (gastrointestinal microbiota) and human health. The emergence of a microbiota-gut-brain axis to describe the complex networks and relationship between the gastrointestinal microbiota and host reflects the major influence this environment may have in brain health and disorders of the central nervous system (CNS). Bidirectional communication between the microbiota and the CNS occurs through autonomic, neuroendocrine, enteric, and immune system pathways. Potential neurobiological mechanisms through which disruptions in this network may impact health and disease include hypothalamic-pituitary-adrenal (HPA)-axis activation, and altered activity of neurotransmitter and immune systems. Perturbations of the gut microbial community have already been implicated in multiple host diseases such as obesity, diabetes, and inflammation, while recent evidence suggests a potential role of the microbiota-gut-brain axis in neuropsychiatric disorders, such as depression and anxiety. Here, we review the current literature related to the influence of the gut microbial community on central nervous system function, with a specific focus on anxiety and depressive symptoms. The role of stress and stress-mediated changes in autonomic, neuroendocrine, immune, and neurotransmitter systems are examined, followed by a discussion of the role of the microbiota in novel gastrointestinal-based treatment options for the prevention and treatment of brain-based disorders such as anxiety and depression.

Exercise is a Novel Promoter of Intestinal Health and Microbial Diversity.

Imbalances in the gut microbiota contribute to chronic gut inflammatory diseases. Interestingly, exercise can improve gut health, but generally, little is known about the underlying mechanisms involved. This article represents a conceptual model illustrating exercise's role in diversifying the gut microbiota to improve gut and systemic health.

The Effect of Diet and Exercise on Intestinal Integrity and Microbial Diversity in Mice.

BACKGROUND: The gut microbiota is now known to play an important role contributing to inflammatory-based chronic diseases. This study examined intestinal integrity/inflammation and the gut microbial communities in sedentary and exercising mice presented with a normal or high-fat diet. METHODS: Thirty-six, 6-week old C57BL/6NTac male mice were fed a normal or high-fat diet for 12-weeks and randomly assigned to exercise or sedentary groups. After 12 weeks animals were sacrificed and duodenum/ileum tissues were fixed for immunohistochemistry for occludin, E-cadherin, and cyclooxygenase-2 (COX-2). The bacterial communities were assayed in fecal samples using terminal restriction fragment length polymorphism (TRFLP) analysis and pyrosequencing of 16S rRNA gene amplicons. RESULTS: Lean sedentary (LS) mice presented normal histologic villi while obese sedentary (OS) mice had similar villi height with more than twice the width of the LS animals. Both lean (LX) and obese exercise (OX) mice duodenum and ileum were histologically normal. COX-2 expression was the greatest in the OS group, followed by LS, LX and OX. The TRFLP and pyrosequencing indicated that members of the Clostridiales order were predominant in all diet groups. Specific phylotypes were observed with exercise, including Faecalibacterium prausnitzi, Clostridium spp., and Allobaculum spp. CONCLUSION: These data suggest that exercise has a strong influence on gut integrity and host microbiome which points to the necessity for more mechanistic studies of the interactions between specific bacteria in the gut and its host.

The Kaiser Permanente experience with ultrasound-guided percutaneous endovascular abdominal aortic aneurysm repair.

BACKGROUND: This study was conducted to determine the effect of ultrasound (US)-guided percutaneous access for percutaneous endovascular abdominal aortic aneurysm repair (PEVAR) on conversion to open repair by femoral cutdown. We also sought to identify other risk factors associated with failure of percutaneous access and conversion to femoral cutdowns. METHODS: This is a single-center, retrospective review of 101 patients who underwent PEVAR between January 1, 2005 and July 31, 2009 (56 months). Risk factors that were evaluated for unsuccessful PEVAR included gender, age (≤65 and ≥66 years), US-guided percutaneous access, mechanical failure, abdominal aortic aneurysm size, and the following comorbidities: diabetes, hypertension, vessel calcification, and obesity (body mass index: ≥30 kg/m(2)). RESULTS: There were 10 (9.9%) conversions from percutaneous to femoral cutdown, yielding a success rate of 90.1% for a total percutaneous approach. Each converted patient had one groin converted, resulting in a cutdown rate per groin of 10/202 (5%). There were no 30-day mortalities. Univariate analysis showed that hypertension (P = 0.261), age ≥66 years (P = 0.741), current smoking history (P = 0.649), past smoking history (P = .093), diabetes (P = 0.908), vessel calcification (P = 0.8281), and body mass index ≥30 kg/m(2) (P = 0.052) did not significantly predict conversion to endovascular aortic aneurysm repair (EVAR). Mechanical failure significantly predicted conversion to cutdown EVAR (P = 0.0002), whereas US-guided percutaneous access influenced successful PEVAR (P = 0.030). Multivariate analysis showed that mechanical failure significantly predicted conversion to cutdown EVAR (P = 0.003) and US-guided percutaneous access influenced successful PEVAR (P = 0.040) after adjusting for smoking history and obesity. CONCLUSION: PEVAR is a viable option for aortic aneurysm repair that may be improved with US-guided percutaneous access by reducing the rate of femoral cutdowns.

Bifurcated endograft repair of ilio-iliac arteriovenous fistula secondary to lumbar diskectomy.

Ilio-iliac arteriovenous (AV) fistula is a rare complication after lumbar diskectomy. Endovascular repair of such fistulas is a growing trend in vascular surgery. This is a case report of an endovascular exclusion of an ilio-iliac AV fistula in a 51-year-old male. This man presented with high-output congestive heart failure and ascites. The AV fistula was discovered 17 years after a lumbar diskectomy. Computed topography (CT) revealed a right common iliac artery pseudoaneurysm connecting to the left common iliac vein. The fistula was repaired using a bifurcated Gore Excluder endograft. There were follow-up CT scans at 6 and 10 months confirming exclusion of the AV fistula. Endovascular AV fistula repair offers a safe, effective method for managing ilio-iliac AV fistulas.