Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults

Abstract

ObjectiveThe colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults.DesignTo investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults.ResultsPropionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group.ConclusionsThese data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans.Trial registration numberNCT00750438.

Prebiotic Dietary Fiber and Gut Health: Comparing the In Vitro Fermentations of Beta-Glucan, Inulin and Xylooligosaccharide.

“…Although no mechanism has been identified, and studies show conflicting results [38], elevated serum propionate concentrations have been shown to have a hypocholesterolaemic effect [39]. Propionate may also play an influential role in satiety, although mechanisms still remain unclear [40,41]. Cholesterol-lowering properties of beta-glucans may be limited to effects from the upper-GI, although many propionate-producing bacteria have a preference to fermenting various types of beta-glucans (Bacteroides, Prevotella, Clostridium) based on the presence of genes responsible for endo-β-glucanase enzyme production [42].…”

Gut-brain signaling in energy homeostasis: the unexpected role of microbiota-derived succinate

“…For instance, mice and rats fed a butyrateenriched diet have increased thermogenesis and energy expenditure (Gao et al 2009), as well as improved glucose tolerance (Lin et al 2012, De Vadder et al 2014. Human studies using acute and long-term administration of the inulin-propionate ester, which can be metabolized to propionate in the colon, have shown that GLP-1 and PYY secretion were increased, concomitantly with reduced calorie intake and weight gain (Chambers et al 2015).…”

Colonic delivery of nutrients for management of blood glucose in type 2 diabetes patients

“…No effect of single-dose glutamine on glycemia was observed in the Gribble studies, which is in accordance with the findings in this current study. However, studies on bariatric surgery [34] and on administration of propionate to the colon [35] suggest that chronic improvement of GLP-1 secretion will improve insulin sensitivity and glucose tolerance, in addition to reducing weight. Therefore, it is anticipated that the chronic treatment of the colon with L-glutamine, a known gut hormone secretagogue, will have a clinically significant effect on glucose tolerance.…”