Genetics of diabetic microvascular disease

Publisher Copyright: © 2020 John Wiley & Sons, Inc.Diabetic microvascular complications, affecting the kidneys, retina, and the nervous system, are a heavy burden for both the diabetic individual and society. The complications seem to cluster in families suggesting a genetic component in their pathogenesis. However, the actual genetic factors have long remained unknown. During the past few years, major advances have been made with large-scale genetic studies that have identified common genetic risk factors, e.g. in the AFF3 and CNKSR3 gene loci affecting the risk of diabetic kidney disease (DKD) end-stage renal disease. There is increasing evidence that genetic factors affecting kidney disease in non-diabetic individuals also affect the risk in individuals with type 2 diabetes (T2D), while less evidence is found for individuals with type 1 diabetes (T1D). While genetic explorations for diabetic retinopathy remain limited in sample size, a recent genome-wide association study (GWAS) identified variants associated with retinopathy on the GRB2 gene. Nevertheless, the field is still lacking strong validated genetic markers. In the future, better phenotyping, larger studies, and exploration of the rare variation are essential to identify the genetic causes behind diabetic microvascular complications, and to understand the interplay between genes and environment.Peer reviewe

The effects of human milk oligosaccharides on gut microbiota, metabolite profiles and host mucosal response in patients with irritable bowel syndrome

Background: Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2′-O-fucosyllactose and lacto-N-neotetraose (2′FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients. Methods: Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2′FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined. Results: Moderate changes in fecal, but not mucosal, microbial composition (β-diversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2′FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2′FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance. Conclusion: Supplementation with 2′FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2′FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health

Erratum: In Vivo Generation of Post-infarct Human Cardiac Muscle by Laminin-Promoted Cardiovascular Progenitors (Cell Reports (2019) 26(12) (3231–3245.e9), (S2211124719302694), (10.1016/j.celrep.2019.02.083))

10.1016/j.celrep.2020.107714Cell Reports31810771