Therapeutic Potential of GLP-2 Analogs in Gastrointestinal Disorders: Current Knowledge, Nutritional Aspects, and Future Perspectives.

PURPOSE OF REVIEW: Although Glucagon-like peptide (GLP)-1 receptor agonists have been used for almost two decades in the treatment of diabetes mellitus type 2 and, lately, in obesity, recent years have seen an increasing interest in the pharmacological agonism of other proglucagon-derived peptides, including GLP-2. Herein, we aimed to review the available evidence on the effects of GLP-2 agonism from animal and clinical studies. Furthermore, we summarize the current clinical applications of GLP-2 agonists among patients with intestinal failure associated with short bowel syndrome (SBS-IF) as well as potential future expansion of their indications to other intestinal disorders. RECENT FINDINGS: Evidence from preclinical studies has highlighted the cellular trophic and functional beneficial actions of GLP-2 on small intestinal and colonic mucosa. Subsequently, pharmacologic agonism of GLP-2 has gathered interest for the treatment of patients with conditions pertaining to the loss of intestinal anatomical and/or functional integrity to a degree requiring parenteral support, collectively referred to as intestinal failure. GLP-2 analogs positively influence nutrient absorption in animal models and humans, although continued therapy is likely needed for sustained effects. The degradation-resistant GLP-2-analog teduglutide has received approval for the treatment of SBS-IF, in which it may decisively reduce patient dependency on parenteral support and improve quality of life. Another two longer-acting analogs, glepaglutide and apraglutide, are currently undergoing phase III clinical trials. The use of GLP-2 analogs is effective in the management of SBS-IF and may show promise in the treatment of other severe gastrointestinal disorders associated with loss of effective intestinal resorptive surface area.

Vitamin D and Obesity: Current Evidence and Controversies.

PURPOSE OF REVIEW: Evidence from observational studies suggests that obesity is associated with low vitamin D. As both obesity and hypovitaminosis D present an alarmingly increased prevalence worldwide, there is an intense research interest to clarify all aspects of this association. This review summarizes current evidence from meta-analyses investigating vitamin D status in obesity, including the effects of weight loss and bariatric surgery on vitamin D status and the outcomes of vitamin D supplementation on body weight. We also discuss potential pathophysiologic mechanisms and important controversies. RECENT FINDINGS: Data from meta-analyses consistently support an inverse association of vitamin D levels with body weight. However, the impact of weight loss on improving vitamin D status is small, while studies on the supplementation with vitamin D after bariatric surgery have shown conflicting results regarding vitamin D status. Moreover, interventional studies do not support a beneficial effect of vitamin D supplementation on body weight. These findings warrant a cautious interpretation due to important methodological limitations and confounding factors, such as high heterogeneity of studies, variable methods of determination of vitamin D and definition of deficiency/insufficiency, use of various adiposity measures and definitions of obesity, and inadequate adjustment for confounding variables influencing vitamin D levels. The underlying pathogenetic mechanisms associating low vitamin D in obesity include volumetric dilution, sequestration into adipose tissue, limited sunlight exposure, and decreased vitamin D synthesis in the adipose tissue and liver. Experimental studies have demonstrated that low vitamin D may be implicated in adipose tissue differentiation and growth leading to obesity either by regulation of gene expression or through modulation of parathyroid hormone, calcium, and leptin. Obesity is associated with low vitamin D status but weight loss has little effect on improving this; vitamin D supplementation is also not associated with weight loss. Evidence regarding vitamin D status after bariatric surgery is contradicting. The link between vitamin D and obesity remains controversial due to important limitations and confounding of studies. More research is needed to clarify the complex interplay between vitamin D and adiposity.

Probiotics, Prebiotics, Synbiotics, Postbiotics, and Obesity: Current Evidence, Controversies, and Perspectives.

PURPOSE OF REVIEW: In this review, we summarize current evidence on gut microbiome and obesity; we discuss the role of probiotics, prebiotics, synbiotics, and postbiotics in obesity prevention and management; and we highlight and analyze main limitations, challenges, and controversies of their use. RECENT FINDINGS: Overall, the majority of animal studies and meta-analyses of human studies examining the use of probiotics and synbiotics in obesity has shown their beneficial effects on weight reduction and other metabolic parameters via their involvement in gut microbiota modulation. Bifidobacterium and Lactobacillus strains are still the most widely used probiotics in functional foods and dietary supplements, but next generation probiotics, such as Faecalibacterium prausnitzii, Akkermansia muciniphila, or Clostridia strains, have demonstrated promising results. On the contrary, meta-analyses of human studies on the use of prebiotics in obesity have yielded contradictory results. In animal studies, postbiotics, mainly short-chain fatty acids, may increase energy expenditure through induction of thermogenesis in brown adipose tissue as well as browning of the white adipose tissue. The main limitations of studies on biotics in obesity include the paucity of human studies; heterogeneity among the studied subgroups regarding age, gender, and lifestyle; and use of different agents with potential therapeutic effects in different formulations, doses, ratio and different pharmacodynamics/pharmacokinetics. In terms of safety, the supplementation with prebiotics, probiotics, and synbiotics has not been associated with serious adverse effects among immune-competent individuals, with the exception of the use of probiotics and synbiotics in immunocompromised patients. Further large-scale Randomized Controlled Trials (RCTs) in humans are required to evaluate the beneficial properties of probiotics, prebiotics, synbiotics, and postbiotics; their ideal dose; the duration of supplementation; and the durability of their beneficial effects as well as their safety profile in the prevention and management of obesity.