Latest research on fibre and gut health

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1 Latest research on fibre and gut health Kevin Whelan PhD Professor of Dietetics King s College

2 Problem #1: Evolving definitions 1970 s Dietary fibre Plant polysaccharides and lignin that are resistant to hydrolysis by the digestive enzymes 1990 s NSP Cellulose and non-cellulosic polysaccharides that are the major component of the plant cell wall 2000 s Dietary fibre CHO polymers (from food, extracted from food or synthetic) with DP 10, which are not hydrolysed by small intestinal enzymes (some flexibility for DP 3-9) SACN, 2015 All non-digestible carbohydrates with DP of 3 plus lignin

3 Problem #1: Evolving definitions, evolving recommendations SACN, 2015 Dietary reference value for total dietary fibre = 30 g/d Reduced risk of disease Wider 95% CI beyond 30 g/d

4 Problem #2: fibre interventions vary, and we eat food and diets Specific dose Specific composition Convenient presentation Natural Not medicalised Benefits to global diet Fibre supplements Pharmacological Nutraceutical Food interventions Dried fruit High fibre cereal Dietary advice Tailored to individual

5 Problem #2: fibre interventions vary, and we eat food and Lockyear et al, Nutr Bull 2016; 41:

6 Problem #2: fibre interventions vary, and we eat food and diets Lockyear et al, Nutr Bull 2016; 41:

7 Problem #3: numerous mechanisms = diverse functions Mineral absorption Glycaemic index Fermentation Short-chain fatty acids Body weight Immune function Dietary intake Microbiome Prebiotic effect Appetite Stool bulking Gut transit time

8 Problem #3: numerous mechanisms = diverse functions Lockyear et al, Nutr Bull 2016; 41:

9 Hierarchy of scientific evidence Stool bulking Constipation Colorectal cancer Irritable bowel syndrome Gut microbiome

10 Stool bulking : Fibre increases stool Rose et al, Crit Rev Environ Sci Tech, 2015; 45:

11 Stool output and food interventions: a meta-analysis of prunes Increase stool frequency by 1.0 stools/wk ( ) Lever et al, Alim Pharm Ther, 2014; 40: No impact on stool consistency 0.3 ( ) (on 7-point scale towards looser stools)

12 Stool output and food interventions: a randomised controlled trial of prunes Mean (SD) Control (n=35) 80 g/d (n=37) 120 g/d (n=32) P value ANCOVA Stool weight (g/d) 109 (61.4) 114 (70.5) 135 (71.4) Stool frequency (per wk) 5.5 (2.2) 7.0 (3.9) 5.7 (1.6) Stool consistency (Bristol) 3.9 (1.1) 3.8 (1.2) 3.6 (1.0) Whole gut transit time (h) 36.3 (28.9) 32.8 (27.3) 39.5 (29.4) Lever et al, (in press)

13 Constipation in the general population 41 study populations (261,040 subjects) Pooled prevalence of constipation = 14% (12%-17%) Suares and Ford, Am J Gastro, 2011; 106:

14 Mechanisms of fibre in constipation

15 Fibre supplements in constipation: meta-analysis Increase stool frequency SMD 0.39 ( ) (significant heterogeneity) Improves stool consistency SMD 0.35 Christodoulides, Alim Pharm Ther, 2016; 44:

16 Fibre supplements in constipation: meta-analysis Why the variation in Christodoulides, Alim Pharm Ther, 2016; 44:

17 Colorectal cancer: Fibre associated with reduced risk Actual UK intakes UK recommended intake For every extra 7 g/d of fibre someone eats, 8% lower risk of colorectal cancer (RR 0.92, P=0.002) SACN report (2015)

18 Irritable bowel syndrome

19 IBS and fibre: meta-analysis Non-fermentable No effect 14 RCTs (906 pts) Relative risk of being symptomatic after fibre = RR 0.86 Mixed fermentable Overall beneficial effect Food-based fibres Possible effect Moayeddi, Am J Gastro 2014; 109:

20 The problem of fibre in Eswaran, Am J Gastro. 2013; 108:

21 Dr Megan Rossi King s College London IBS and fibre: how to improve effectiveness Poorly fermentable Moderately fermentable Highly fermentable Single fibre Inulin Single fibre Co-administration Co-administration Psyllium Inulin + Psyllium Nopal

22 Volume of gas produced IBS and fibre: how to improve effectiveness Inulin Psyllium F6_ave F7_ave F8D_ave 20.0 Nopal

23 Fermentable Oligosaccharides (fructans) Disaccharides (lactose) Monosaccharides (fructose) And (α-galacto-oligosaccharides) Polyols (sorbitol, mannitol, xylitol)

24 @ProfWhelan Staudacher & Whelan, 2017, Gut

25 Low FODMAP diet advice Identifying suitable foods

26 Low FODMAP diet impacts microbiota Staudacher, J Nutrition 2012; 142: Halmos, Gut, 2015, 64: Baseline Bennet, Gut (in press) LFD

27 Low FODMAP diet advice vs placebo diet advice Randomised controlled trial Staudacher et al, DDW 2016

28 Low FODMAP diet advice vs placebo diet advice What effect of the probiotic on microbiome? Bacteria (from 16S sequencing) (each of these genera are contained within VSL#3) Staudacher et al, DDW 2016

29 Microbiota of the gut Stomach 10 3 bacteria/ml (1,000 per ml) e.g. Helicobacter pylori Small intestine 10 6 bacteria/ml (1,000,000 per ml) e.g. Lactobacilli, gram positive cocci Colon bacteria/g (1,000,000,000,000 per g) e.g. Bacteroides, clostridia, bifidobacteria, eubacteria, enterobacteria etc etc etc

30 Microbiota: beneficial functions in health Power et al, Brit J Nutr 2014; 111:

31 @ProfWhelan Koh, Cell, 2016: 16; 1332

32 Diet associated with different microbiome: Case-control study Burkina Faso Florence Italy De Filipo, Proc Nat Acd Sci 2010; 107:

33 Short-term diet affects microbiota Plant vs animal diets David et al, Nature, 2014; 505(7484):

34 Prebiotics Non-digestible food components that selectively stimulate the growth and/or activity of one or a limited number of microbial genera, species or strains in the gut microbiota that confer health benefits to the host ILSI Expert Panel on Prebiotics

35 Fibre and effects on microbiome: meta-analysis Daniel So Dr Katrina Campbell Bifidobacteria SMD = 0.56 (95% CI ) P < Validated prebiotics SMD 0.79 (P< ) Candidate prebitoics SMD 0.63 (P=0.22) But albeit with considerable heterogeneity (I 2 = 84%) Non-prebiotics SMD 0.25 (P=0.10)

36 Fibre and effects on microbiome: meta-analysis

37 Habitual fibre intake and the prebiotic effect: RCT Massey University, NZ Genelle Healey Prof Jane Coad

38 Habitual fibre intake and the prebiotic effect: RCT

39 Habitual fibre intake and the prebiotic effect: RCT

40 Fibre has lots of other benefits: SACN report For every extra 7 g/d of fibre eaten: 9% lower risk of cardiovascular disease (RR 0.91, P<0.001) 9% lower risk of heart attack (RR 0.91, P<0.001) 7% lower risk of stroke (RR 0.93, P=0.002) 6% lower risk of type 2 diabetes (RR 0.94,

41 Summary Definitions, recommendations and research on the impact on gut health for fibre have evolved over recent decades Fibre increases stool bulk (stool weight), and in constipation it can increase stool frequency Epidemiological associations of fibre intake and reduced risk of CRC Some fibres may reduce symptoms in IBS, but highly fermentable fibres might exacerbate (FODMAPs) Fibre impacts on the gut microbiome, but largely relates to prebiotic fibres Habitual fibre intake may impact the effect of prebiotics on the gut microbiome

42 King s College London Dr Megan Rossi Dr Ellen Lever Dr Eirini Dimidi Dr Miranda Lomer Dr Peter Irving Dr Mark Scott (Queen Mary University) Stephan Christodoulides (Queen Mary University) Genelle Healey (Massey University, NZ) Dr Chrissie Butts (Massey University, NZ) Dr Rinki Murphy (University of Aukland, NZ) Dr Louise Brough (Massey University, NZ) Prof Jane Coad (Massey University, NZ) Jennette Higgs Michele Sadler Prof Robin Spiller (University of Nottingham) Dr Luca Marciani (University of Nottingham) Dr Giles Major (University of Nottingham) Dr Jose Remes-Troche (University of Verracruz, Mexico) Dr Cathriona Edwards (Quadram Institute) Dr Fred Warren (Quadram Institute) Daniel So (Bond University, Aus) Dr Katrina Campbell (Bond University, Aus) Prof Mark Morrison (University of Queensland, Aus) Dr Heidi Staudacher (University of Queensland, Aus)