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Adaptation of colonic fermentation and glucagon-like peptide-1 secretion with increased wheat fibre intake for 1 year in hyperinsulinaemic human subjects

  • Kristin R. Freeland (a1), Charlotte Wilson (a1) and Thomas M. S. Wolever (a1) (a2)

High cereal fibre intake is associated with reduced risk for type 2 diabetes, but wheat fibre had little or no effect on glycaemic control or oral glucose tolerance in clinical trials lasting 4–12 weeks. To explain this discrepancy, we hypothesised that colonic adaptation to increased wheat fibre intake takes many months but eventually results in increased SCFA production and glucagon-like peptide-1 (GLP-1) secretion. Thus, the primary objective was to determine the time-course of the effects of increased wheat fibre intake on plasma acetate, butyrate and GLP-1 concentrations in hyperinsulinaemic human subjects over 1 year. Subjects with fasting plasma insulin ≥ 40 pmol/l were randomly assigned by computer to receive either a high-wheat fibre cereal (fibre group; 24 g fibre/d; twenty assigned; six dropped out, fourteen included) or a low-fibre cereal (control group; twenty assigned; six dropped-out, fourteen included) daily for 1 year. Acetate, butyrate and GLP-1 were measured during 8 h metabolic profiles performed every 3 months. There were no differences in body weight in the fibre group compared with the control group. After 9 months baseline-adjusted mean 8 h acetate and butyrate concentrations were higher on the high-fibre than the control cereal (P < 0·05). After 12 months on the high-fibre cereal, baseline-adjusted mean plasma GLP-1 was 1·3 (95 % CI 0·4, 2·2) pmol/l (P < 0·05) higher than at baseline (about 25 % increase) and 1·4 (95 % CI 0·1, 2·7) pmol/l (P < 0·05) higher than after 12 months on control. It is concluded that wheat fibre increased SCFA production and GLP-1 secretion in hyperinsulinaemic humans, but these effects took 9–12 months to develop. Since GLP-1 may increase insulin sensitivity and secretion, these results may provide a mechanism for the epidemiological association between high cereal fibre intake and reduced risk for diabetes.

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      Adaptation of colonic fermentation and glucagon-like peptide-1 secretion with increased wheat fibre intake for 1 year in hyperinsulinaemic human subjects
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*Corresponding author: Dr Thomas Wolever, fax +1 416 978 5882, email
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1 Ludwig, DS, Pereira, MA, Kroenke, CH, et al. (1999) Dietary fiber, weight gain, and cardiovascular risk factors in young adults. JAMA 282, 15391546.
2 Liu, S, Willet, WC, Manson, JE, et al. (2003) 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 87, 920927.
3 Schulze, MB, Schulz, M, Heidemann, C, et al. (2007) Fiber and magnesium intake and incidence of type 2 diabetes. Arch Intern Med 167, 956965.
4 Liu, S, Stampfer, MJ, Hu, FB, et al. (1999) Whole-grain consumption and risk of coronary heart disease: results from the Nurses' Health Study. Am J Clin Nutr 70, 412419.
5 Weickert, MO & Pfeiffer, AFH (2008) Metabolic effects of dietary fiber consumption and prevention of diabetes. J Nutr 138, 439442.
6 Weickert, MO, Mohlig, M, Koebnick, C, et al. (2005) Impact of cereal fibre on glucose-regulating factors. Diabetologia 48, 23432353.
7 Weickert, MO, Möhlig, M, Schöfl, C, et al. (2006) Cereal fiber improves whole-body insulin sensitivity in overweight and obese women. Diabetes Care 29, 775780.
8 Munoz, JM, Sandstead, HH & Jacob, RA (1979) Effects of dietary fiber on glucose tolerance of normal men. Diabetes 28, 496502.
9 Kestin, M, Moss, R, Clifton, PM, et al. (1990) Comparative effects of three cereal brans on plasma lipids, blood pressure, and glucose metabolism in mildly hypercholesterolemic men. Am J Clin Nutr 52, 661666.
10 Jenkins, DJA, Kendall, CWC, Augustin, LSA, et al. (2002) Effect of wheat bran on glycaemic control and risk factors for cardiovascular disease in type 2 diabetes. Diabetes Care 25, 15221528.
11 Costabile, A, Klinder, A, Fava, F, et al. (2008) Whole-grain wheat breakfast cereal has a prebiotic effect on the human gut microbiota: a double-blind, placebo-controlled, crossover study. Br J Nutr 99, 110120.
12 Wong, JMW, deSouza, R, Kendall, CWC, et al. (2006) Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol 40, 235243.
13 Reimer, RA & McBurney, MI (1996) Dietary fiber modulates intestinal proglucagon messenger ribonucleic acid and postprandial secretion of glucagon-like peptide-1 and insulin in rats. Endocrinology 137, 39483956.
14 Tappenden, KA, Thomson, AB, Wild, GE, et al. (1996) Short-chain fatty acids increase proglucagon and ornithine decarboxylase messenger RNAs after intestinal resection in rats. JPEN 20, 357362.
15 Drucker, DJ (1998) Glucagon-like peptides. Diabetes 47, 159169.
16 Samuel, BS, Hansen, EE, Manchester, JK, et al. (2007) Genomic and metabolic adaptations of Methanobrevibacter smithii to the human gut. PNAS 104, 1064310648.
17 Feng, QY & Chai, LH (2008) A new statistical dynamic analysis on vegetation patterns in land ecosystems. Physica A 387, 35833593.
18 Le Blay, G, Catherine Michel, C, Hervé, M, et al. (1999) Enhancement of butyrate production in the rat caecocolonic tract by long-term ingestion of resistant potato starch. Br J Nutr 82, 419426.
19 Wolever, TMS, Schrade, KB, Vogt, JA, et al. (2002) Do colonic short-chain fatty acids contribute to the long-term adaptation of blood lipids in subjects with type 2 diabetes consuming a high-fiber diet? Am J Clin Nutr 75, 10231030.
20 Wolever, TMS, Radmard, R, Chiasson, J-L, et al. (1995) One-year acarbose therapy raises fasting serum acetate in diabetic patients. Diabet Med 12, 164172.
21 Cummings, JH, Pomare, EW, Branch, WJ, et al. (1987) Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 28, 12211227.
22 Cummings, JH & MacFarlane, GT (1991) The control and consequences of bacterial fermentation in the human colon. J Appl Bacteriol 70, 443459.
23 Cummings, JH (1982) Polysaccharide fermentation in the human colon. Colon and Nutrition: Proceedings of the 32nd Falk Symposium, pp. 91102 [Kasper, H and Goebell, H, editors]. Hingham, MA: MTP Press.
24 Southgate, DAT, Branch, WJ, Hill, MH, et al. (1976) Metabolic responses to dietary supplements of bran. Metabolism 25, 11291135.
25 Clausen, JO, Borch-Johnsen, K, Ibsen, H, et al. (1996) Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians: analysis of the impact of gender, body fat, physical fitness and life-style factors. J Clin Invest 98, 11951209.
26 Chiasson, JL & Rabasa-Lhoret, R (2004) Prevention of type 2 diabetes: insulin resistance and β-cell function. Diabetes 53, Suppl. 3, S34S38.
27 Brindle, PA, Schooley, DA, Tsai, LW, et al. (1988) Comparative metabolism of branched-chain amino acids to precursors of juvenile hormone biogenesis in corpora allata of lepidopterous versus nonlepidopterous insects. J Biol Chem 263, 1065310657.
28 Scheppach, W, Pomare, EW, Elia, M, et al. (1991) The contribution of the large intestine to blood acetate in man. Clin Sci 80, 177182.
29 Smith, RF, Humphrys, S & Hockaday, TD (1986) The measurement of plasma acetate by a manual or automated technique in diabetic and non-diabetic subjects. Ann Clin Biochem 23, 285291.
30 Wolever, TM, Josse, RG, Leiter, LA, et al. (1997) Time of day and glucose tolerance status affect serum short-chain fatty acid concentrations in humans. Metabolism 46, 805811.
31 Adam, A, Levrat-Verny, M-A, Lopez, HW, et al. (2001) Whole wheat and triticale flours with differing viscosities stimulate cecal fermentations and lower plasma and hepatic lipids in rats. J Nutr 131, 17701776.
32 Rémésy, C, Demingé, C & Chartier, F (1980) Origin and utilization of volatile fatty acids in the rat. Reprod Nutr Dev 20, 13391349.
33 Wolever, TMS & Chiasson, JL (2000) Acarbose raises serum butyrate in subjects with impaired glucose tolerance. Br J Nutr 84, 5761.
34 Knudsen, KEB, Serena, A, Canibe, N, et al. (2003) New insight into butyrate metabolism. Proc Nutr Soc 62, 8186.
35 Wolever, TMS & Robb, PA (1992) Effect of guar, pectin, psyllium, soy polysaccharide and cellulose on breath hydrogen and methane in healthy subjects. Am J Gastroenterol 87, 305310.
36 Wolever, TMS, ter Wal, P, Spadafora, P, et al. (1992) Guar, but not psyllium, increases breath methane and serum acetate concentrations in human subjects. Am J Clin Nutr 55, 719722.
37 Cummings, JH, Southgate, DAT, Branch, W, et al. (1978) Colonic response to dietary fibre from carrot, cabbage, apple, bran, and guar gum. Lancet i, 59.
38 El Oufir, LE, Barry, JL, Flourie, B, et al. (2000) Relationships between transit time in man and in vitro fermentation of dietary fiber by fecal bacteria. Eur J Clin Nutr 54, 603609.
39 Christensen, DN, Bach Knudsen, KE, Wolstrup, J, et al. (1999) Integration of ileum cannulated pigs and in vitro fermentation to quantify the effect of diet composition on the amount of short-chain fatty acids available from fermentation in the large intestine. J Sci Food Agric 79, 755762.
40 Boffa, LC, Lupton, JR, Mariani, MR, et al. (1992) Modulation of colonic epithelial cell proliferation, histone acetylation and luminal short-chain fatty acids by variation of dietary fiber (wheat bran) in rats. Cancer Res 52, 59065912.
41 Duncan, SH, Holtrop, G, Lobley, GE, et al. (2004) Contribution of acetate to butyrate formation by human fecal bacteria. Br J Nutr 91, 915923.
42 Kleessen, B, Stoof, G, Proll, J, et al. (1997) Feeding resistant starch affects fecal and caecal microflora and short-chain fatty acids in rats. J Anim Sci 75, 24532462.
43 van Loo, J, Cummings, J, Delzenne, N, et al. (1999) Functional food properties of non-digestible oligosaccharides: a consensus report from the ENDO project (DGXII AIRII-CT94-1095). Br J Nutr 81, 121132.
44 Eissele, R, Göke, R, Willemer, S, et al. (1992) Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin Invest 22, 283291.
45 Massimino, SP, McBurney, MI, Field, CJ, et al. (1998) Fermentable dietary fiber increases GLP-1 secretion and improves glucose homeostasis despite increased intestinal glucose transport capacity in healthy dogs. J Nutr 128, 17861793.
46 Kripke, SA, Fox, AD, Berman, JJ, et al. (1989) Stimulation of intestinal mucosal growth with intracolonic infusion of short-chain fatty acids. JPEN 13, 109116.
47 Cani, PD, Hoste, S, Guiot, Y, et al. (2007) Dietary non-digestible carbohydrates promote L-cell differentiation in the proximal colon of rats. Br J Nutr 98, 3237.
48 Karaki, S, Tazoe, H, Hayashi, H, et al. (2008) Expression of the short-chain fatty acid receptor, GPR 43, in the human colon. J Mol Histol 39, 135142.
49 Rask, E, Olsson, T, Soderberg, S, et al. (2001) Impaired incretin response after a mixed meal is associated with insulin resistance in nondiabetic men. Diabetes Care 24, 16401645.
50 Verdich, C, Toubro, S, Buemann, B, et al. (2001) The role of postprandial release of insulin and incretin hormones in meal-induced satiety – effect of obesity and weight reduction. Int J Obes 25, 12061214.
51 Brubaker, PL & Vranic, M (1987) Fetal rat intestinal cells in monolayer culture: a new in vitro system to study the glucagon-related peptides. Endocrinology 120, 19761985.
52 Anini, Y & Brubaker, PL (2003) Role of leptin in the regulation of glucagon-like peptide-1 secretion. Diabetes 52, 252259.
53 Robertson, MD, Bickerton, AS, Dennis, AL, et al. (2005) Insulin-sensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism. Am J Clin Nutr 82, 559567.
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