Changes in the intestinal microbiome have been associated with obesity and type 2 4 diabetes, in epidemiological studies and studies of the effects of fecal transfer in germ-free mice. We review the mechanisms by which alterations in the intestinal microbiome contribute to development of metabolic diseases, and recent advances, such as the effects of the microbiome on lipid metabolism. Strategies have been developed to modify the intestinal microbiome and reverse metabolic alterations, which might be used as therapies. We discuss approaches that have shown effects in mouse models of obesity and metabolic disorders, and how these might be translated to humans to improve metabolic health.

Gut microbiota plays a role in the pathophysiology of metabolic diseases which also include nonalcoholic fatty liver diseases (NAFLD), through the gut-liver axis. To date, clinical guidelines recommend a weight loss goal of 7 to 10% to improve features of NAFLD.Nevertheless, since this target is not easily achieved by all patients, alternative therapeutic options are currently being evaluated. This review focusses on therapeutics that aims to modulate the gut microbiota and the gut-liver axis. We will herein discuss how probiotics, prebiotics, synbiotic, fecal microbiota transfer, polyphenols, specific diets and exercise interventions have been shown to modify gut microbiota signatures, improve NAFLD outcomes and detail, when available, the different mechanisms by which these beneficial outcomes might occur. Apart from probiotics which have already been tested in human RCTs, most of these potential therapeutics have been studied in animals. Their efficacy still warrants confirmation in humans using appropriate design.

The importance of the postprandial state has been acknowledged, since hyperglycemia and hyperlipidemia are linked with several chronic systemic low-grade inflammation conditions. Humans spend more than 16 h per day in the postprandial state and the postprandial state is acknowledged as a complex interplay between nutrients, hormones and diet-derived metabolites. The purpose of this review is to provide insight into the physiology of the postprandial inflammatory response, the role of different nutrients, the pro-inflammatory effects of metabolic endotoxemia and the anti-inflammatory effects of bile acids. Moreover, we discuss nutritional strategies that may be linked to the described pathways to modulate the inflammatory component of the postprandial response.

The noble gas helium (He) induces cardioprotection in vivo through unknown molecular mechanisms. He can interact with and modify cellular membranes. Caveolae are cholesterol and sphingolipid-enriched invaginations of the plasma-membrane-containing caveolin (Cav) proteins that are critical in protection of the heart. Mice (C57BL/6J) inhaled either He gas or adjusted room air. Functional measurements were performed in the isolated Langendorff perfused heart at 24 h post He inhalation. Electron paramagnetic resonance spectrometry (EPR) of samples was carried out at 24 h post He inhalation. Immunoblotting was used to detect Cav-1/3 expression in whole-heart tissue, exosomes isolated from platelet free plasma (PFP) and membrane fractions. Additionally, transmission electron microscopy analysis of cardiac tissue and serum function and metabolomic analysis were performed. In contrast to cardioprotection observed in in vivo models, the isolated Langendorff perfused heart revealed no protection after He inhalation. However, levels of Cav-1/3 were reduced 24 h after He inhalation in whole-heart tissue, and Cav-3 was increased in exosomes from PFP. Addition of serum to muscle cells in culture or naïve ventricular tissue increased mitochondrial metabolism without increasing reactive oxygen species generation. Primary and lipid metabolites determined potential changes in ceramide by He exposure. In addition to direct effects on myocardium, He likely induces the release of secreted membrane factors enriched in caveolae. Our results suggest a critical role for such circulating factors in He-induced organ protection.

Introduction: Cardiometabolic diseases (CMD) are a group of interrelated disorders such as metabolic syndrome, type 2 diabetes mellitus and cardiovascular diseases (CVD). As the prevalence of these diseases increases globally, efficient new strategies are necessary to target CMD and modifiable risk factors. In the past decade, evidence has accumulated regarding the influence of gut microbiota (GM) on CMD, providing new targets for therapeutic interventions. Areas covered: This narrative review discusses the pathophysiologic link between CMD, GM, and potential microbiota-based targets against atherosclerosis and modifiable risk factors for atherosclerosis. Low-grade inflammation can be induced through GM and its derived metabolites. CMD are influenced by GM and microbiota-derived metabolites such as short-chain fatty acids (SCFA), secondary bile acids, trimethylamine N-oxide (TMAO), and the composition of GM can modulate host metabolism. All of the above can lead to promising therapeutic targets. Expert opinion: Most data are derived from animal models or human association studies; therefore, more translational and interventional research in humans is necessary to validate these promising findings. Reproduced findings such as aberrant microbiota patterns or circulating biomarkers could be targeted depending on individual metabolic profiles, moving toward personalized medicine in CMD. ARTICLE HISTORY

Congenital muscle diseases, such as myopathies or dystrophies, occur relatively frequently, with estimated incidences of up to 4.7 per 100 000 newborns. To diagnose congenital diseases in the early stages of pregnancy, and to interpret the results of increasingly advanced in utero imaging techniques, a profound knowledge of normal human morphological development of the locomotor system and the nervous system is necessary. Muscular development, however, is an often neglected topic or is only described in a general way in embryology textbooks and papers. To provide the required detailed and updated comprehensive picture of embryologic muscular anatomy, three‐dimensional (3D) reconstructions were created based on serial histological sections of a human embryo at Carnegie stage 23 (8 weeks of development, crown–rump length of 23.8 mm), using amira reconstruction software. Reconstructed muscles, tendons, bones and nerves were exported in a 3D‐PDF file to permit interactive viewing. Almost all adult skeletal muscles of the trunk and limbs could be individually identified in their relative adult position. The pectoralis major muscle was divided in three separate muscle heads. The reconstructions showed remarkable highly developed extraocular, infrahyoid and suprahyoid muscles at this age but surprisingly also absence of the facial muscles that have been described to be present at this stage of development. The overall stage of muscle development suggests heterochrony of skeletal muscle development. Several individual muscle groups were found to be developed earlier and in more detail than described in current literature.

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The ketogenic diet is a dietary regime focused on strongly reducing carbohydrate intake and increasing fat intake; leading to a state of ketosis. The ketogenic diet has gained much popularity over the years due to its effects on promoting weight loss, increasing insulin sensitivity and reducing dyslipidaemia. All these factors play a crucial role in the development of cardio-metabolic diseases; one of the greatest health challenges of the time. Moreover, the ketogenic diet has been known to reduce (epileptic) seizure activity. It is still poorly understood how following a ketogenic diet can lead to these beneficial metabolic effects. However, in recent years it has become clear that diet and the gut microbiota interact with one another and thus influence host health. The goal of this review is to summarize the current state of knowledge regarding the beneficial metabolic effects of the ketogenic diet and the role of gut microbiota in these effects.