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Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial.
Chambers, ES, Byrne, CS, Morrison, DJ, Murphy, KG, Preston, T, Tedford, C, Garcia-Perez, I, Fountana, S, Serrano-Contreras, JI, Holmes, E, et al
Gut. 2019;68(8):1430-1438
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Plain language summary
Literature shows that higher intakes of dietary fibre are associated with a reduced risk of type 2 diabetes. The main aim of this study was to elucidate the underlying mechanisms behind improvements in glucose homeostasis following long-term delivery of propionate (a short-chain fatty acid produced by human gut microbiota in response to dietary fibre) to the human colon. The study is a randomised, double-blind, placebo-controlled cross over trial. Fourteen participants randomly received 20 g/day of a low-fermentable fibre control, a high-fermentable fibre control and inulin-propionate ester (IPE) for 42 days each. Results indicate that stool concentrations of short-chain fatty acids were not different following the three supplementation periods. Furthermore, dietary supplementation with 20 g/day IPE promoted no superior impacts on measures of glucose homeostasis compared with inulin (high-fermentable fibre), yet both IPE and inulin improved insulin resistance relative to cellulose (low-fermentable fibre). Authors conclude that manipulating the colonic fermentation profile of a dietary fibre in favour of propionate promotes selective effects on the mechanisms that contribute to metabolic dysregulation.
Abstract
OBJECTIVE To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses. DESIGN Twelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period. RESULTS Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose. CONCLUSION These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation.
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Lifespan modification by glucose and methionine in Drosophila melanogaster fed a chemically defined diet.
Troen, AM, French, EE, Roberts, JF, Selhub, J, Ordovas, JM, Parnell, LD, Lai, CQ
Age (Dordrecht, Netherlands). 2007;(1):29-39
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Abstract
Experimentally restricting dietary calories, while maintaining adequate dietary nutrient content, extends lifespan in phylogenetically diverse species; thus suggesting the existence of conserved pathways which can modify lifespan in response to energy intake. However, in some cases the impact on longevity may depend on the quality of the energy source. In Drosophila, restriction of dietary yeast yields considerable lifespan extension whereas isocaloric restriction of dietary sugar yields only modest extension, indicating that other diet-responsive pathways can modify lifespan in this species. In rodents, restricting intake of a single amino acid - methionine - extends lifespan. Here we show that dietary methionine can modify lifespan in adult female, non-virgin Oregon-R strain Drosophila fed a chemically defined media. Compared to a diet containing 0.135% methionine and 15% glucose, high dietary methionine (0.405%) shortened maximum lifespan by 2.33% from 86 to 84 days and mean lifespan by 9.55% from 71.7 to 64.9 days. Further restriction of methionine to 0.045% did not extend maximum lifespan and shortened mean lifespan by 1.95% from 71.1 to 70.3 days. Restricting glucose from 15% to 5% while holding methionine at a concentration of 0.135%, modestly extended maximum lifespan by 5.8% from 86 to 91 days, without extending mean lifespan. All these diet-induced changes were highly significant (log-rank p < 0.0001). Notably, all four diets resulted in considerably longer life spans than those typically reported for flies fed conventional yeast and sugar based diets. Such defined diets can be used to identify lifespan-modifying pathways and specific gene-nutrient interactions in Drosophila.