Fiber Mixture-specific Effect on Distal Colonic Fermentation and Metabolic Health in Lean but Not in Prediabetic Men

Overview

Journal Gut Microbes

Specialties Gastroenterology
Microbiology

Date 2021 Dec 20

PMID 34923911

Citations 16

Authors

Emanuel E Canfora

Gerben D A Hermes

Mattea Muller

Jacco Bastings

Elaine E Vaughan

Marco A van den Berg

Jens J Holst

Koen Venema

Erwin G Zoetendal

Ellen E Blaak

Affiliations

Soon will be listed here.

Abstract

Infusions of the short-chain fatty acid (SCFA) acetate in the distal colon improved metabolic parameters in men. Here, we hypothesized that combining rapidly and slowly fermentable fibers will enhance distal colonic acetate production and improve metabolic health. In vitro cultivation studies in a validated model of the colon were used to identify fiber mixtures that yielded high distal colonic acetate production. Subsequently, in two randomized crossover studies, lean and prediabetic overweight/obese men were included. In one study, participants received supplements of either long-chain inulin+resistant starch (INU+RS), INU or maltodextrin (PLA) the day prior to a clinical investigation day (CID). The second trial studied beta glucan+RS (BG+RS) versus BG and PLA. During each CID, breath hydrogen, indirect calorimetry, plasma metabolites/hormones were assessed during fasting and postprandial conditions. Additionally, fecal microbiota composition and SCFA were determined. In prediabetic men, INU+RS increased plasma acetate compared to INU or PLA ( < .05), but did not affect metabolic parameters. In lean men, INU+RS increased breath hydrogen and fasting plasma butyrate, which was accompanied by increased energy expenditure, carbohydrate oxidation and PYY and decreased postprandial glucose concentrations (all < .05) compared to PLA. BG+RS increased plasma butyrate compared to PLA ( < .05) in prediabetic individuals, but did not affect other fermentation/metabolic markers in both phenotypes. Fiber-induced shifts in fecal microbiota were individual-specific and more pronounced with INU+RS versus BG+RS. Administration of INU+RS (not BG+RS) the day prior to investigation improved metabolic parameters in lean but not in prediabetic individuals, demonstrating that effects were phenotype- and fiber-specific. Further research should study whether longer-term supplementation periods are required to elicit beneficial metabolic health in prediabetic individuals. Trial registration numbers: Clinical trial No. NCT03711383 (Inulin study) and Clinical trial No. NCT03714646 (Beta glucan study).

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References

Serino M, Luche E, Gres S, Baylac A, Berge M, Cenac C . Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota. Gut. 2011; 61(4):543-53. PMC: 3292714. DOI: 10.1136/gutjnl-2011-301012. View

Sandberg J, Bjorck I, Nilsson A . Effects of whole grain rye, with and without resistant starch type 2 supplementation, on glucose tolerance, gut hormones, inflammation and appetite regulation in an 11-14.5 hour perspective; a randomized controlled study in healthy subjects. Nutr J. 2017; 16(1):25. PMC: 5401465. DOI: 10.1186/s12937-017-0246-5. View

den Besten G, Gerding A, van Dijk T, Ciapaite J, Bleeker A, van Eunen K . Protection against the Metabolic Syndrome by Guar Gum-Derived Short-Chain Fatty Acids Depends on Peroxisome Proliferator-Activated Receptor γ and Glucagon-Like Peptide-1. PLoS One. 2015; 10(8):e0136364. PMC: 4546369. DOI: 10.1371/journal.pone.0136364. View

Boets E, Gomand S, Deroover L, Preston T, Vermeulen K, De Preter V . Systemic availability and metabolism of colonic-derived short-chain fatty acids in healthy subjects: a stable isotope study. J Physiol. 2016; 595(2):541-555. PMC: 5233652. DOI: 10.1113/JP272613. View

Everard A, Lazarevic V, Gaia N, Johansson M, Stahlman M, Backhed F . Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity. ISME J. 2014; 8(10):2116-30. PMC: 4163056. DOI: 10.1038/ismej.2014.45. View

Blaak E, Canfora E, Theis S, Frost G, Groen A, Mithieux G . Short chain fatty acids in human gut and metabolic health. Benef Microbes. 2020; 11(5):411-455. DOI: 10.3920/BM2020.0057. View

Koh A, De Vadder F, Kovatcheva-Datchary P, Backhed F . From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Cell. 2016; 165(6):1332-1345. DOI: 10.1016/j.cell.2016.05.041. View

Bouter K, Bakker G, Levin E, Hartstra A, Kootte R, Udayappan S . Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects. Clin Transl Gastroenterol. 2018; 9(5):155. PMC: 5968024. DOI: 10.1038/s41424-018-0025-4. View

Torang S, Bojsen-Moller K, Svane M, Hartmann B, Rosenkilde M, Madsbad S . In vivo and in vitro degradation of peptide YY3-36 to inactive peptide YY3-34 in humans. Am J Physiol Regul Integr Comp Physiol. 2016; 310(9):R866-74. PMC: 5000776. DOI: 10.1152/ajpregu.00394.2015. View

10.

McNelis J, Lee Y, Mayoral R, van der Kant R, Johnson A, Wollam J . GPR43 Potentiates β-Cell Function in Obesity. Diabetes. 2015; 64(9):3203-17. PMC: 4542437. DOI: 10.2337/db14-1938. View

11.

Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K, Maeda T . The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat Commun. 2013; 4:1829. PMC: 3674247. DOI: 10.1038/ncomms2852. View

12.

Freeland K, Wolever T . Acute effects of intravenous and rectal acetate on glucagon-like peptide-1, peptide YY, ghrelin, adiponectin and tumour necrosis factor-alpha. Br J Nutr. 2009; 103(3):460-6. DOI: 10.1017/S0007114509991863. View

13.

Canfora E, van der Beek C, Hermes G, Goossens G, Jocken J, Holst J . Supplementation of Diet With Galacto-oligosaccharides Increases Bifidobacteria, but Not Insulin Sensitivity, in Obese Prediabetic Individuals. Gastroenterology. 2017; 153(1):87-97.e3. DOI: 10.1053/j.gastro.2017.03.051. View

14.

Reynolds A, Mann J, Cummings J, Winter N, Mete E, Te Morenga L . Carbohydrate quality and human health: a series of systematic reviews and meta-analyses. Lancet. 2019; 393(10170):434-445. DOI: 10.1016/S0140-6736(18)31809-9. View

15.

Frost G, Sleeth M, Sahuri-Arisoylu M, Lizarbe B, Cerdan S, Brody L . The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat Commun. 2014; 5:3611. PMC: 4015327. DOI: 10.1038/ncomms4611. View

16.

van der Beek C, Canfora E, Lenaerts K, Troost F, Olde Damink S, Holst J . Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men. Clin Sci (Lond). 2016; 130(22):2073-2082. DOI: 10.1042/CS20160263. View

17.

Brooks L, Viardot A, Tsakmaki A, Stolarczyk E, Howard J, Cani P . Fermentable carbohydrate stimulates FFAR2-dependent colonic PYY cell expansion to increase satiety. Mol Metab. 2017; 6(1):48-60. PMC: 5220466. DOI: 10.1016/j.molmet.2016.10.011. View

18.

Adrian T, Ferri G, Fuessl H, Polak J, Bloom S . Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology. 1985; 89(5):1070-7. DOI: 10.1016/0016-5085(85)90211-2. View

19.

Delzenne N, Neyrinck A, Backhed F, Cani P . Targeting gut microbiota in obesity: effects of prebiotics and probiotics. Nat Rev Endocrinol. 2011; 7(11):639-46. DOI: 10.1038/nrendo.2011.126. View

20.

Lim J, Henry C, Haldar S . Vinegar as a functional ingredient to improve postprandial glycemic control-human intervention findings and molecular mechanisms. Mol Nutr Food Res. 2016; 60(8):1837-49. DOI: 10.1002/mnfr.201600121. View