Dietary protein, red meat and colorectal cancer risk

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1 Dietary protein, red meat and colorectal cancer risk Dr Silvia Gratz Research Fellow Gut Health - Microbiology The Rowett Institute University of Aberdeen

2 Processed meat is classified as human carcinogen Lyon, France, 26 October 2015 The International Agency for Research on Cancer (IARC), the cancer agency of the WHO, has evaluated the carcinogenicity of the consumption of red meat and processed meat. Red meat After thoroughly reviewing the accumulated scientific literature, a Working Group of 22 experts from 10 countries convened by the IARC Monographs Programme classified the consumption of red meat as probably carcinogenic to humans (Group 2A), based on limited evidence that the consumption of red meat causes cancer in humans and strong mechanistic evidence supporting a carcinogenic effect. This association was observed mainly for colorectal cancer, but associations were also seen for pancreatic cancer and prostate cancer. Processed meat Processed meat was classified as carcinogenic to humans (Group 1), based on sufficient evidence in humans that the consumption of processed meat causes colorectal cancer. Carcinogens in meat: nitrosamines, heterocyclic amines

3 WCRF colorectal cancer and diet

4 Overview intestinal digestion and fermentation Small intestine Proximal Large intestine Distal Faeces Food Digestion of CHO, protein, fat by host enzymes Absorption Non-digestible CHO (RS, NSP, FOS) Residual protein SCFA gradient SCFA Gases other metabolites ph gradient Excretion of undigested CHO, Lignin, unabsorbed nutrients Absorption Carbohydrate SCFA (acetate, propionate, butyrate) Bacterial fermentation products Protein SCFA (acetate, propionate, butyrate) BCFA (iso-butyrate, iso-valerate) Gases (CO 2, CH 4, H 2 ) Gases (CO 2, CH 4, H 2 ) Bacterial biomass Bacterial biomass Ammonia, Phenols, Indoles, Amines, Sulfides Scott KP, Gratz SW, Sheridan P, Flint HJ & Duncan SH (2013): The influence of diet on gut microbiota. Pharmacol Res 69(1):52-60.

5 Focus of the work Identify foods/ingredients that drive colonic fermentation and shift faecal metabolome towards health-promoting profiles Specifically focus on the balance between dietary carbohydrate/fibre and dietary protein/meat Faecal SCFA profiles Endogenously formed NOC

6 Effect of carbohydrates, fibre, meat on intestinal fermentation products Variable HRM HRM+HAMSB Faecal output (g/d) 241 ± ± 30 Randomised cross-over clinical trial 23 healthy volunteers 300 g cooked lean red meat 40g HAMSB 4 week intervention periods Faecal ph 7.2 ± ± 0.1 Acetate (µmol/g) 51.0 ± ± 4.6 Propionate (µmol/g) 15 ± 1.5 a 20 ± 1.5 b Butyrate (µmol/g) 14 ± 1.9 a 21 ± 2.7 b Total SCFA (µmol/g) 88 ± 7.5 a 106 ± 8.3 b BCFA 4.5 ± 0.4 a 3.7 ± 0.3 b Phenol (µg/g) 2.0 ± ± 0.6 p-cresol (µg/g) 67 ± 5 a 50 ± 6 b Le Leu RK, et al. B J Nutr (2015) 114(2): Ammonia (µmol/g) 15 ± ± 1.0

7 Study design MTD NSP NPWL HPMC HPLC Body weight maintenance diet Non-starch polysaccharide MTD Normal protein weight loss diet High protein moderate carbohydrate weight loss diet High protein low carbohydrate weight loss diet

8 Average intake (g/d) Diet composition Fat CHO Protein Protein intakes g/d CHO intake g/d Fat intake g/d Energy MJ/d MTD NSP NPWL HPMC HPLC Body weight maintenance diet Non-starch polysaccharide MTD Normal protein weight loss diet High protein moderate carbohydrate weight loss diet High protein low carbohydrate weight loss diet

9 Effect of dietary protein and carbohydrate on faecal fermentation products % of total SCFA Faecal NOC (ng/g) MTD NPWL HPWL * * Isobutyrate Isovalerate Butyrate Proprionate Acetate a b c MTD NPWL HPWL Diet High protein weight loss diets change the faecal short chain fatty acid profile (butyrate, isobutyrate & isovalerate) compared to normal protein weight loss diet or a balanced body weight maintenance diet Both normal protein and high protein weight loss diets increase faecal NOC

10 Faecal NOC (ng/g) Faecal Iso-butyrate (%) Faecal butyrate (%) Faecal Iso-butyrate (%) Effect of dietary protein and carbohydrate on faecal fermentation products MTD NPWL HPWL MTD NPWL HPWL Dietary CHO (g/d) Dietary CHO (g/d) MTD NPWL HPWL Dietary CHO (g/d) Dietary protein (g/d) MTD NPWL HPWL Dietary CHO main driver of colonic CHO and protein fermentation Dietary protein has secondary effect

11 Correlation of dietary components and NOC Ac Prop Bu TSCFA Ac% Prop% Bu% IsoBu IsoVal TBCFA IsoBu% IsoVal% TBCFA% PAA IAA 4OHPLA NOC CHO Strach Sugars DF NSP Total protein Non-meat protein Red meat White meat Total meat CHO/protein Holtrop G, et al (2012): J Nutr 142(9):

12 Random effects linear regression AIC Akaike s Information Criterion, used to assess model fit (lower AIC means improved fit) NOC N-nitroso compounds NO 3 Nitrate NSP Non-starch polysaccharide VitC Vitamin C

13 NOC change Log NOC % Observed 0.31 Predicted %

14 Improved prediction of endogenous formation of NOC Terms in model ENOC ug/d = *MeatFe NOC change LogNOC % Observed Predicted % - More complex models predict higher proportion of ENOC than simple models - Our dataset better reflects complex interaction between nutrients & food groups Jakszyn P., et al. Carcinogenesis (2006) 27, 7,

15 Summary & Conclusions Diet strongly influences faecal fermentation products CHO increase faecal SCFA CHO decrease faecal protein breakdown products Dietary protein has little effect on BCFA Diet drives endogenous NOC formation Red meat strongest contributor Nitrate/Vitamin C ratio also increases formation Dietary fibre might protect against endogenous formation More complex statistical models allow us to assess the effect of multiple dietary components intestinal fermentation Dietary carbohydrate/fibre rather than protein intake drives colonic microbial fermentation

16 Acknowledgements Rowett Gut Health - Microbiology: Tony Richardson, Sylvia Duncan, Harry Flint, Wendy Russell, Lorraine Scobbie Rowett Obesity & Metabolic Health: Gerald Lobley, Alex Johnstone Colleagues from Flinders Medical Centre, Adelaide SA: Graham Young, Richard LeLeu, Jean Winter BioSS: Grietje Holtrop Funders RESAS (Scottish Government), RSE, WCRF

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