Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2015 Nov;64(11):1744-54.
doi: 10.1136/gutjnl-2014-307913. Epub 2014 Dec 10.

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

Edward S Chambers  1 , Alexander Viardot  2 , Arianna Psichas  1 , Douglas J Morrison  3 , Kevin G Murphy  4 , Sagen E K Zac-Varghese  4 , Kenneth MacDougall  5 , Tom Preston  3 , Catriona Tedford  5 , Graham S Finlayson  6 , John E Blundell  6 , Jimmy D Bell  7 , E Louise Thomas  7 , Shahrul Mt-Isa  8 , Deborah Ashby  8 , Glen R Gibson  9 , Sofia Kolida  9 , Waljit S Dhillo  4 , Stephen R Bloom  4 , Wayne Morley  10 , Stuart Clegg  10 , Gary Frost  1
Affiliations
Randomized Controlled Trial

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

Edward S Chambers et al. Gut. 2015 Nov.

Abstract

Objective: The 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.

Design: To 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.

Results: Propionate 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.

Conclusions: These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans.

Trial registration number: NCT00750438.

Keywords: APPETITE; COLONIC FERMENTATION; GUT HORMONES; NUTRITIONAL SUPPLEMENTATION; OBESITY.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Propionate increases peptide YY (PYY) and glucagon like peptide-1 (GLP-1) release from primary human colonic cells and inulin-propionate ester supplementation delivers propionate to the colon in vivo. Cells isolated from human colonic tissue were incubated with increasing concentrations of propionate. (A) PYY and (B) GLP-1 levels were measured in the supernatants and lysed cells by radioimmunoassay. Percentage gut hormone release per well is expressed relative to the basal release measured (n=4–6). (C) The increase in breath H2 at 240 min suggests that >80% of the labelled propionate entered the colon. (D) Plasma acetate and propionate 13C enrichment (δ13C per mil) at baseline and 360 min. Plasma propionate was significantly more enriched at 360 min whereas no difference was seen in acetate enrichment. Total plasma propionate (E) and acetate (F) concentrations (µmol/L) at baseline and 360 min. Data are presented as mean±SEM, *p<0.05, ***p<0.001.
Figure 2
Figure 2
Acute inulin-propionate ester supplementation increases plasma peptide YY (PYY) and glucagon like peptide-1 (GLP-1) levels and reduces energy intake in humans. (A) The mean reduction in energy intake following inulin-control versus inulin-propionate ester. (B) A reduction in energy intake occurred in 16 of the 20 volunteers. (C–F) Plasma gut hormone levels following acute supplementation of inulin-control versus inulin-propionate ester. Arrows indicate standardised meals. Dotted lines signify the time point after which >80% inulin-propionate ester enters the colon as determined by the enrichment of 13C in expired air and breath H2 methodology (figure 1C). Data are presented as mean±SEM, *p<0.05, **p<0.01. AUC, area under the curve.
Figure 3
Figure 3
The effect of 24 weeks inulin-control and inulin-propionate ester supplementation on weight gain, liver fat content and gut hormone response. (A) The proportion of subjects who gained 3% or more and 5% or more of their baseline weight at 24 weeks. (B) Intrahepatocellular lipid (IHCL) content at baseline and following 24 weeks of inulin-control and inulin-propionate ester supplementation in subjects with non-alcoholic fatty liver disease (NAFLD). Subjects were identified as having NAFLD on the basis of an IHCL content >5.5% at baseline. Postprandial plasma (C) peptide YY (PYY) and (D) GLP-1 release at baseline and following 24 weeks of inulin-control and inulin-propionate ester supplementation. Data are presented as mean±SEM, *p<0.05.
Figure 4
Figure 4
The effect of inulin-propionate ester on the gut microbiota. Bacterial concentrations expressed in Log10 cells/mL culture fluid enumerated using fluorescent in situ hybridisation (FISH) targeting (A) Bifidobacterium spp (Bif164), (B) Bacteroides/Prevotella (Bac303), (C) Atopobium cluster (Ato291), (D) Lactobacillus/Enterococcus (Lab158), (E) Clostridium histolyticum (Chis150) and (F) Eubacterium rectale/Clostridium coccoides (Erec482) at 0 h, 10 h, 24 h, 34 h and 48 h anaerobic, pH controlled faecal batch culture fermentation with control (no substrate), inulin-control and inulin-propionate ester. Data are presented as mean±SEM (n=3), *<0.05, †<0.001, ‡<0.0001 with respect to the 0 h sample.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Hussain SS, Bloom SR. The regulation of food intake by the gut-brain axis: implications for obesity. Int J Obes (Lond) 2013;37:625–33. - PubMed
    1. Zhao L. The gut microbiota and obesity: from correlation to causality. Nat Rev Microbiol 2013;11:639–47. - PubMed
    1. Cani PD. Metabolism in 2013: the gut microbiota manages host metabolism. Nat Rev Endocrinol 2014;10:74–6. - PubMed
    1. Ridaura VK, Faith JJ, Rey FE, et al. . Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 2013;341:1241214. - PMC - PubMed
    1. Liou AP, Paziuk M, Luevano JM Jr, et al. . Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med 2013;5:178ra41. - PMC - PubMed

Publication types

Associated data