Learning from the research on amebiasis and gut microbiome: Is stimulation by gut flora essential for effective neutrophil mediated protection from external pathogens?

Amebiasis, caused by intestinal infection with Entamoeba histolytica, is one of the leading causes of parasite infection-related mortality and morbidity globally. Although its pathogenesis, including determinant factors of infection outcome, remains unclear, recent clinical data indicate that the gut microbiome plays a role in determining the severity of amebiasis. Recently, we investigated the effects of the gut microbiome on neutrophil mediated protection from E. histolytica infection using a mouse model. We identified that surface expression of CXCR2 on neutrophils was diminished in mice with dysbiosis, which resulted in decreased neutrophil recruitment to the infection site, allowing more aggressive intestinal tissue damage by E. histolytica. Our results indicated that oxidase activity during E. histolytica infection was also diminished after dysbiosis, consistent with the results from prior research. Thus, the gut microbiome plays an important role in regulating neutrophil phenotype when fighting against external pathogens.     

Resistance to obesity and resistance to atherosclerosis: Is there a metabolic link?

AimThis review deals with the question whether resistance to obesity affects resistance to atherosclerosis.Data synthesisResistance to diet-induced obesity in inbred mouse strains involves an adequate response to Leptin, the main regulator of the energy balance cycle. Leptin, an adipokine with both central and peripheral targets, regulates food intake and energy expenditure. Adequate response to leptin involves repression of stearoyl-CoA desaturase, activation of Amp-activated protein-kinase and uncoupling proteins, resulting in fatty acid oxidation and energy expenditure. Most of the obesity-resistant strains are also resistant to atherosclerosis, but so far no information concerning the response to the leptin cycle is available in these strains when bred onto a LDLR^−/− or apoE^−/− background. Recent studies in mouse strains on an atherosclerosis permissive background have identified genetic links between obesity and atherosclerosis. Moreover, information derived from studies on mice was applied in order to learn about the metabolic effectors in humans and is included in this review.ConclusionsThe data presented in this review provide recent information concerning metabolic pathways that play an important role in the regulation of energy balance, a prerequisite for resistance to obesity. Hopefully they will provide a background for future genetic studies involved in resistance to atherosclerosis.     

Juvenile idiopathic arthritis and the gut microbiome: Where are we now?

In recent decades, because of advances in technology there has been an explosion of knowledge on how microbiome affects human health. In most chronic immune-inflammatory diseases, alterations in gut microbiome has been shown. The successful use of faecal microbial transplants for the treatment of clostridium difficile associated diarrhoea has also paved the way for novel therapies.Gut microbiome is affected by early life events like the mode of delivery, breast feeding, the use of antibiotics, etc. and that may have an indirect effect on the developing immune system as well as on the predisposition to juvenile idiopathic arthritis (JIA). Multiple studies have found altered gut microbiome in JIA though no single organism or microbial community has been found to be associated with JIA. In JIA, attempts to modify gut microbiome by using probiotics, exclusive enteral nutrition and other modalities have had variable success.The current review discusses the current data available on gut microbiome in different categories of JIA and how this knowledge can translate into new therapies.     

Is China facing an obesity epidemic and the consequences? The trends in obesity and chronic disease in China

BACKGROUND: Over the past two decades, China has enjoyed impressive economic development, and her citizens have experienced many remarked changes in their lifestyle. These changes are often associated with an increase in obesity and chronic disease. METHODS: In this meta-analysis, based on nationally representative data, we studied the current prevalence of obesity and the trends in obesity, mortality and morbidity in China. RESULTS: Between 1992 and 2002, the prevalence of overweight and obesity increased in all gender and age groups and in all geographic areas. Using the World Health Organization body mass index cut points, the combined prevalence of overweight and obesity increased from 14.6 to 21.8%. The Chinese obesity standard shows an increase from 20.0 to 29.9%. The annual increase rate was highest in men aged 18-44 years and women aged 45-59 years (approximately 1.6 and 1.0% points, respectively). In general, male subjects, urban residents, and high-income groups had a greater increase. With the increase in overweight and obesity, obesity-, and diet-related chronic diseases (e.g., hypertension, cardiovascular disease (CVD), and type 2 diabetes) also increased over the past decade and became a more important preventable cause of death. Hypertension increased from 14.4% in 1991 to 18.8% in 2002 in adults; in older adults aged 35-74 years, it increased from 19.7 to 28.6%. Between 1993 and 2003, the prevalence of CVD increased from 31.4 to 50.0%; diabetes increased from 1.9 to 5.6%. During 1990-2003, although total mortality rate (per 100 000) decreased, overall the mortality rate and contribution (as percentages) to total death of obesity-related chronic disease increased, in particular, in rural areas. Mortality rate (per 100 000) of CVD increased from 128 to 145 and its contribution to total death, 27 to 32%, in rural areas; the figures decreased slightly in urban areas. The mortality rate of 'nutrition, endocrinology and metabolism-related disease' (NEMD) increased in both rural and urban areas between 1990 and 2000, 8.0 to 10.6 and 4.9 to 5.3, respectively. The current prevalence of hypertension, dyslipidaemia, metabolic syndrome, and diabetes among Chinese adults is approximately 20, 20, 15, and 3%, respectively. CONCLUSION: The prevalence of overweight and obesity and obesity-related chronic diseases have increased in China in the past decade. Our findings provide useful information for the projection of future trends and the formulation of national strategies and programmes that can address the challenges of the growing obesity and chronic disease epidemic.     

The gut microbiome–derived metabolite trimethylamine N-oxide modulates neuroinflammation and cognitive function with aging

GeroScience - Aging is associated with declines in cognitive performance, which are mediated in part by neuroinflammation, characterized by astrocyte activation and higher levels of...     

Is circulating osteocalcin related to adipokines and overweight/obesity in children and adolescents?

Osteocalcin (OC) has recently been described to be involved in the regulation of glucose and energy metabolism. We aimed to evaluate whether or not OC serum levels were related to parameters of overweight and serum adipokine levels of healthy children and adolescents in dependence on gender and pubertal stage.In a cross sectional study (Leipzig Schoolchildren Project) 497 healthy, caucasian children and adolescents of all pubertal stages were included. We measured anthropometric data height, weight, fat mass, waist-to-hip ratio, pubertal development and performed biochemical analyses of osteocalcin, leptin, adiponectin and resistin serum levels by immunoassay.OC serum levels were associated with pubertal development achieving peak values at Tanner stage 3. There was no significant association of OC serum levels with overweight and obesity as measured by BMI and WHR. In addition, OC demonstrated no significant association with serum levels of leptin and adiponectin but a negative association with resistin in both genders independent of pubertal stages (r= - 0.329, p<0.0001).We conclude that there is no major relationship between OC and metabolism, but we can not exclude minor relations between OC and metabolism. The negative relationship with serum resistin levels might rather point to a link between OC and inflammatory states.     

Is turtle longevity linked to enhanced mechanisms for surviving brain anoxia and reoxygenation?

We suggest that the processes that protect the turtle brain against anoxia and subsequent reoxygenation might also contribute to turtle longevity since many of them are linked to age related neurodegeneration. In the turtle the mechanisms for conserving ion channel function are particularly robust. The anoxic turtle brain avoids excitatory neurotransmitter toxicity by maintaining a balance between dopamine and glutamate-release and still active uptake mechanisms. In the anoxic turtle brain the inhibitory tone is strengthened through a sustained rise in extracellular GABA, and a corresponding increase in the density of GABA(A) receptors. The turtle has enhanced mechanisms that protect against the formation of ROS and mechanisms to protect from ROS damage. As many of these may be selectively activated during anoxia and recovery, the turtle could serve as a useful model to identify and investigate mechanisms for activating key protection and rescue mechanisms implicated in aging.     

From obesity to diabetes: why, when and who?

Obesity is considered as the most important risk factor for type 2 diabetes. We will briefly discuss why does obesity predispose to diabetes, when does diabetes occur in obese subjects and who among obese individuals is particularly prone to develop diabetes. Obesity, especially intraabdominal adiposity, is associated with increased FFA plasma concentrations which exert a major negative effect on insulin sensitivity at both muscular and hepatic sites. Various metabolic, haemodynamic and hormonal theories have been proposed to explain insulin resistance in obese subjects. A specific role of TNF-alpha has been recently suggested. However, besides insulin resistance, defective insulin secretion is a prerequisie for the development of overt type 2 diabetes. Both lipotoxicity and glucotoxicity may initiate and perpetuate a vicious circle responsible for the metabolic deterioration. Diabetes occurs as a late phenomenon in obesity and is preceded by years of impaired glucose tolerance. The progression to diabetes is heralded by an inability of the B cell to maintain its previously high rate of insulin secretion in response to glucose in face of insulin resistance. This propensity to develop type 2 diabetes may be genetically determined and/or triggered by environmental factors. The evolution from obesity to diabetes represents a continuum that progresses through different phases in which defects in both insulin action and insulin secretion play a critical interaction and must be looked at in concert.     

The Class Effect: Is It Relevant to Geriatrics?

The formulary of medications available today provides a remarkable range of choices to all prescribers and their patients. In some ways, choices have become easier to make, whereas in other ways, choosing has become a nightmare of dueling considerations. One approach to simplification has relied on class effect. The hypothesis is that drugs within a pharmacological class all work similarly, have similar advantages and disadvantages, and are-to a large extent-interchangeable. If one develops familiarity with one or two agents in a class, that is all one needs to know, because there is little difference between agents within a drug class. The question is whether this approach based on class effect is relevant to geriatrics.     

The obesity paradox: fact or fiction?

Although the adverse health consequences of obesity in the general population have been well documented, recent evidence suggests that obesity is associated with better outcomes in patients with heart failure (HF). Studies of patients with HF that specifically examined the impact of body mass index (BMI) on outcomes have suggested the existence of an "obesity paradox." However, closer examination of these studies raises important questions on the validity of the paradox. First, the diagnosis of HF in obese patients, particularly when made using clinical variables, may not be accurate; the obese patients in these studies may actually be "healthier" than their nonobese comparators. Second, the deleterious effects of cachexia, rather than the salutary ones of obesity, are likely the main reason for the inverse correlation between BMI and HF outcome, especially once the underlying biologic mechanisms behind cachexia and obesity in patients with HF are considered. Furthermore, few studies have specifically examined the more severely obese population (BMI >35 kg/m(2)) when assessing outcomes, and those that have suggest that severely obese patients may have worse outcomes than patients with normal weights or those who are mildly obese. Therefore, a "U-shaped" outcome curve according to BMI for patients with HF may actually exist, in which mortality is greatest in cachectic patients; lower in normal, overweight, and mildly obese patients; but higher again in more severely obese patients. Further prospective studies assessing the impact of more marked degrees of obesity on outcomes in patients with HF are needed to more conclusively determine whether the obesity paradox truly exists.