Decreased Enterobacteriaceae translocation due to gut microbiota remodeling mediates the alleviation of premature aging by a high‐fat diet

Aging‐associated microbial dysbiosis exacerbates various disorders and dysfunctions, and is a major contributor to morbidity and mortality in the elderly, but the underlying cause of this aging‐related syndrome is confusing. SIRT6 knockout (SIRT6 KO) mice undergo premature aging and succumb to death by 4 weeks, and are therefore useful as a premature aging research model. Here, fecal microbiota transplantation from SIRT6 KO mice into wild‐type (WT) mice phenocopies the gut dysbiosis and premature aging observed in SIRT6 KO mice. Conversely, an expanded lifespan was observed in SIRT6 KO mice when transplanted with microbiota from WT mice. Antibiotic cocktail treatment attenuated inflammation and cell senescence in KO mice, directly suggesting that gut dysbiosis contributes to the premature aging of SIRT6 KO mice. Increased Enterobacteriaceae translocation, driven by the overgrowth of Escherichia coli, is the likely mechanism for the premature aging effects of microbiome dysregulation, which could be reversed by a high‐fat diet. Our results provide a mechanism for the causal link between gut dysbiosis and aging, and support a beneficial effect of a high‐fat diet for correcting gut dysbiosis and alleviating premature aging. This study provides a rationale for the integration of microbiome‐based high‐fat diets into therapeutic interventions against aging‐associated diseases.     

Diet leaves a genetic signature in a keystone member of the gut microbiota

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A high‐fat diet reverses metabolic disorders and premature aging by modulating insulin and IGF1 signaling in SIRT6 knockout mice

Mammalian sirtuin 6 (SIRT6) is involved in the regulation of many essential processes, especially metabolic homeostasis. SIRT6 knockout mice undergo premature aging and die at age ~4 weeks. Severe glycometabolic disorders have been found in SIRT6 knockout mice, and whether a dietary intervention can rescue SIRT6 knockout mice remains unknown. In our study, we found that at the same calorie intake, a high‐fat diet dramatically increased the lifespan of SIRT6 knockout mice to 26 weeks (males) and 37 weeks (females), reversed multi‐organ atrophy, and reduced body weight, hypoglycemia, and premature aging. Furthermore, the high‐fat diet partially but significantly normalized the global gene expression profile in SIRT6 knockout mice. Regarding the mechanism, excessive glucose uptake and glycolysis induced by the SIRT6 deficiency were attenuated in skeletal muscle through inhibition of insulin and IGF1 signaling by the high‐fat diet. Similarly, fatty acids but not ketone bodies inhibited glucose uptake, glycolysis, and senescence in SIRT6 knockout fibroblasts, whereas PI3K inhibition antagonized the effects of a high‐fatty‐acid medium in vitro. Overall, the high‐fat diet dramatically reverses numerous consequences of SIRT6 deficiency through modulation of insulin and IGF1 signaling, providing a new basis for elucidation of SIRT6 and fatty‐acid functions and supporting novel therapeutic approaches against metabolic disorders and aging‐related diseases.     

Deciphering the diet of a wandering spider (Phoneutria boliviensis; Araneae: Ctenidae) by DNA metabarcoding of gut contents

Arachnids are the most abundant land predators. Despite the importance of their functional roles as predators and the necessity to understand their diet for conservation, the trophic ecology of many arachnid species has not been sufficiently studied. In the case of the wandering spider, Phoneutria boliviensis F. O. Pickard‐Cambridge, 1897, only field and laboratory observational studies on their diet exist. By using a DNA metabarcoding approach, we compared the prey found in the gut content of males and females from three distant Colombian populations of P. boliviensis. By DNA metabarcoding of the cytochrome c oxidase subunit I (COI), we detected and identified 234 prey items (individual captured by the spider) belonging to 96 operational taxonomic units (OTUs), as prey for this wandering predator. Our results broaden the known diet of P. boliviensis with at least 75 prey taxa not previously registered in fieldwork or laboratory experimental trials. These results suggest that P. boliviensis feeds predominantly on invertebrates (Diptera, Lepidoptera, Coleoptera, and Orthoptera) and opportunistically on small squamates. Intersex and interpopulation differences were also observed. Assuming that prey preference does not vary between populations, these differences are likely associated with a higher local prey availability. Finally, we suggest that DNA metabarcoding can be used for evaluating subtle differences in the diet of distinct populations of P. boliviensis, particularly when predation records in the field cannot be established or quantified using direct observation.     

Relevance to prenatal diagnosis of the identification of a human Y/autosome translocation by Y-chromosome-specific in situ hybridisation

Routine cytogenetic analysis of an amniotic fluid sample revealed a large brightly fluorescent region in the short arm of chromosome 14 in an otherwise normal male karyotype (46,XY,14p+ + +). This site was also present in the paternal karyotype. In situ hybridisation to a Y-chromosome-specific DNA probe confirmed that the father had a Y/14 translocation. The incidence of two hybridisation bodies (large hybridisation sites), detecting both the translocated Y chromatin and the normal Y chromosome, was lower in interphase nuclei (44.3%) than in metaphase spreads (95.2%). The relevance of these observations to the potential use of in situ hybridisation to interphase nuclei for prenatal diagnosis is discussed.     

Effect of a high fructose diet on the activities of enzymes implicated in the conversion of fructose to glucose by the liver and the intestinal mucosa of the rat

The activity of enzymes implicated in the metabolic pathway of fructose to glucose conversion was shown in rat liver and intestine. In rats on normal diet, the specific activity of glucose-6-phosphatase, fructokinase, fructose-1,6-diphosphatase and triokinase was low in the intestine confirming that sugar conversion is not operative in this organ. In rats on a fructose diet, all the specific enzymatic activities tested were increased except for the hepatic triokinase and triose phosphate isomerase and for the intestinal triose phosphate isomerase. The intestine acquires the possibility to transform fructose to glucose by modifying the activities of enzymes implicated in the same metabolic pathway as that intervening in the liver.     

Arthrospira maxima prevents the acute fatty liver induced by the administration of simvastatin,ethanol and a hypercholesterolemic diet to mice

An evident fatty liver, corroborated morphologically and chemically, was produced in CD-1 mice after five daily doses of simvastatin 75 mg/Kg body weight, a hypercholesterolemic diet and 20 percent ethanol in the drinking water. After treating the animals, they presented serum triacylglycerols levels five times higher than the control mice, total lipids, cholesterol and triacylglycerols in the liver were 2, 2 and 1.5 times higher, respectively, than in control animals. When Arthrospira maxima was given with diet two weeks prior the onset of fatty liver induction, there was a decrement of liver total lipids (40%), liver triacylglycerols (50%) and serum triacylglycerols (50%) compared to the animals with the same treatment but without Arthrospira maxima. In addition to the mentioned protective effect, the administration of this algae, produced a significant increase (45%) in serum high density lipoproteins. The mechanism for this protective effect was not established in these experiments.