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...

Overview

Journal Gut

Specialty Gastroenterology

Date 2019 Apr 12

PMID 30971437

Citations 150

Authors

Edward S Chambers

Claire S Byrne

Douglas J Morrison

Kevin G Murphy

Tom Preston

Catriona Tedford

Isabel Garcia-Perez

Sofia Fountana

Jose Ivan Serrano-Contreras

Elaine Holmes

Catherine J Reynolds

Jordie F Roberts

Rosemary J Boyton

Daniel M Altmann

Julie A K McDonald

Julian R Marchesi

Arne N Akbar

Natalie E Riddell

Gareth A Wallis

Gary S Frost

Affiliations

Soon will be listed here.

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.

Citing Articles

Impact of Dietary Fiber on Inflammation in Humans.

Kabisch S, Hajir J, Sukhobaevskaia V, Weickert M, Pfeiffer A Int J Mol Sci. 2025; 26(5).

PMID: 40076626 PMC: 11900212. DOI: 10.3390/ijms26052000.

Maternal dietary inulin intake during late gestation and lactation ameliorates intestinal oxidative stress in piglets with the involvements of gut microbiota and bile acids metabolism.

Lu D, Feng C, Pi Y, Ye H, Wu Y, Huang B Anim Nutr. 2025; 20:318-331.

PMID: 40034460 PMC: 11872665. DOI: 10.1016/j.aninu.2024.11.016.

The Inflammatory Mechanism of Parkinson's Disease: Gut Microbiota Metabolites Affect the Development of the Disease Through the Gut-Brain Axis.

Gao A, Lv J, Su Y Brain Sci. 2025; 15(2).

PMID: 40002492 PMC: 11853208. DOI: 10.3390/brainsci15020159.

Orally Administrated Inulin-Modified Nanozymes for CT-Guided IBD Theranostics.

Li X, Cao L, Li J, Li Z, Ma H, Cheng S Int J Nanomedicine. 2025; 20:2119-2131.

PMID: 39990289 PMC: 11846537. DOI: 10.2147/IJN.S497558.

Polysaccharides: The Sweet and Bitter Impacts on Cardiovascular Risk.

Kalisz G, Popiolek-Kalisz J Polymers (Basel). 2025; 17(3).

PMID: 39940607 PMC: 11820192. DOI: 10.3390/polym17030405.

References

Ludwig D, Pereira M, Kroenke C, Hilner J, Van Horn L, Slattery M . Dietary fiber, weight gain, and cardiovascular disease risk factors in young adults. JAMA. 1999; 282(16):1539-46. DOI: 10.1001/jama.282.16.1539. View

Pereira M, Jacobs Jr D, Pins J, Raatz S, Gross M, Slavin J . Effect of whole grains on insulin sensitivity in overweight hyperinsulinemic adults. Am J Clin Nutr. 2002; 75(5):848-55. DOI: 10.1093/ajcn/75.5.848. View

Macfarlane S, Macfarlane G . Regulation of short-chain fatty acid production. Proc Nutr Soc. 2003; 62(1):67-72. DOI: 10.1079/PNS2002207. View

Liu S, Willett W, Manson J, Hu F, Rosner B, Colditz G . Relation between changes in intakes of dietary fiber and grain products and changes in weight and development of obesity among middle-aged women. Am J Clin Nutr. 2003; 78(5):920-7. DOI: 10.1093/ajcn/78.5.920. View

Robertson M, Bickerton A, Dennis A, Vidal H, Frayn K . Insulin-sensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism. Am J Clin Nutr. 2005; 82(3):559-67. DOI: 10.1093/ajcn.82.3.559. View

Herder C, Haastert B, Muller-Scholze S, Koenig W, Thorand B, Holle R . Association of systemic chemokine concentrations with impaired glucose tolerance and type 2 diabetes: results from the Cooperative Health Research in the Region of Augsburg Survey S4 (KORA S4). Diabetes. 2005; 54 Suppl 2:S11-7. DOI: 10.2337/diabetes.54.suppl_2.s11. View

Kim C, Park H, Kawada T, Kim J, Lim D, Hubbard N . Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes (Lond). 2006; 30(9):1347-55. DOI: 10.1038/sj.ijo.0803259. View

Cani P, Neyrinck A, Fava F, Knauf C, Burcelin R, Tuohy K . Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007; 50(11):2374-83. DOI: 10.1007/s00125-007-0791-0. View

Ge H, Li X, Weiszmann J, Wang P, Baribault H, Chen J . Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids. Endocrinology. 2008; 149(9):4519-26. DOI: 10.1210/en.2008-0059. View

10.

Schwiertz A, Taras D, Schafer K, Beijer S, Bos N, Donus C . Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring). 2009; 18(1):190-5. DOI: 10.1038/oby.2009.167. View

11.

Laparra J, Sanz Y . Bifidobacteria inhibit the inflammatory response induced by gliadins in intestinal epithelial cells via modifications of toxic peptide generation during digestion. J Cell Biochem. 2010; 109(4):801-7. DOI: 10.1002/jcb.22459. View

12.

Wu X, Ma C, Han L, Nawaz M, Gao F, Zhang X . Molecular characterisation of the faecal microbiota in patients with type II diabetes. Curr Microbiol. 2010; 61(1):69-78. DOI: 10.1007/s00284-010-9582-9. View

13.

Karpe F, Dickmann J, Frayn K . Fatty acids, obesity, and insulin resistance: time for a reevaluation. Diabetes. 2011; 60(10):2441-9. PMC: 3178283. DOI: 10.2337/db11-0425. View

14.

Cheng S, Rhee E, Larson M, Lewis G, McCabe E, Shen D . Metabolite profiling identifies pathways associated with metabolic risk in humans. Circulation. 2012; 125(18):2222-31. PMC: 3376658. DOI: 10.1161/CIRCULATIONAHA.111.067827. View

15.

Stancakova A, Civelek M, Saleem N, Soininen P, Kangas A, Cederberg H . Hyperglycemia and a common variant of GCKR are associated with the levels of eight amino acids in 9,369 Finnish men. Diabetes. 2012; 61(7):1895-902. PMC: 3379649. DOI: 10.2337/db11-1378. View

16.

Flint H, Scott K, Duncan S, Louis P, Forano E . Microbial degradation of complex carbohydrates in the gut. Gut Microbes. 2012; 3(4):289-306. PMC: 3463488. DOI: 10.4161/gmic.19897. View

17.

Dewulf E, Cani P, Claus S, Fuentes S, Puylaert P, Neyrinck A . Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women. Gut. 2012; 62(8):1112-21. PMC: 3711491. DOI: 10.1136/gutjnl-2012-303304. View

18.

Ferrannini E, Natali A, Camastra S, Nannipieri M, Mari A, Adam K . Early metabolic markers of the development of dysglycemia and type 2 diabetes and their physiological significance. Diabetes. 2012; 62(5):1730-7. PMC: 3636608. DOI: 10.2337/db12-0707. View

19.

Liou A, Paziuk M, Luevano Jr J, Machineni S, Turnbaugh P, Kaplan L . Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med. 2013; 5(178):178ra41. PMC: 3652229. DOI: 10.1126/scitranslmed.3005687. View

20.

Buhl M, Bosnjak E, Vendelbo M, Gjedsted J, Nielsen R, K-Hafstrom T . Direct effects of locally administered lipopolysaccharide on glucose, lipid, and protein metabolism in the placebo-controlled, bilaterally infused human leg. J Clin Endocrinol Metab. 2013; 98(5):2090-9. DOI: 10.1210/jc.2012-3836. View