Gut microbiota in IBS and its modification by diet: probiotics, prebiotics and low FODMAP diet Kevin Whelan PhD RD FBDA Professor of Dietetics Department of Nutritional Sciences King s College London Nutritional Sciences @ProfWhelan #EFAD2018
Irritable bowel syndrome 5 10% of the UK population Significant impact on individuals, families and healthcare
IBS: complex, inter-related pathophysiology Collins et al, Nature Gastro Hepatol, 2014; 11: 497 505
Microbiome in IBS: Systematic review of case-control studies (qpcr) Liu, Digest Liver Disease 2017; 49: 331 337 Bifidobacterium SMD= 1.17 P<0.001 (I 2 =79.3%) Lactobacillus SMD= 0.85 P<0.001 (I 2 =28%) Faecalibacterium prausnitzii SMD= 1.05 P<0.001 (I 2 =0.0%) No difference in: Bacteroides Prevotella Escherichia coli or other genera/species
Microbiome in IBS: Differences in microbiome only in some with IBS Differences in microbiome are different Sequencing 37 IBS vs 20 matched controls Jeffery, Gut, 2012; 61: 997 1006
Microbiome in IBS: Differences in enterotype, richness and gas Tap et al, Gastroenterology 2017; 152: 111 123
Microbiome in IBS: Differences also in mucosal microbiome Bifidobacteria negatively correlate with number of days of pain ( 0.409, P=0.031) More days of pain, less bifidobacteria Less bifidobacteria, more days of pain Parkes et al NeuroGastro Motility 2012; 24; 31 9
Role for microbiome in IBS: mechanistic Diet-induced gas production & symptoms Major et al, Gastroenterology 2017;152:124 133
Evolution of diet research in IBS Dr Eirini Dimidi Dimidi et al, Curr Opin Clin Nutr 2017; 20: 456 463
Probiotics Live micro organisms that, when administered in adequate amounts, confer a health benefit on the host (FAO/WHO, 2002)
Probiotics in IBS: systematic review of systematic reviews and BDA Guidelines McKenzie, J Hum Nutr Diet 2016; 29, 576 592 @ProfWhelan #EFAD2018
Probiotics in IBS: systematic review of systematic reviews and BDA Guidelines McKenzie, J Hum Nutr Diet 2016; 29, 576 592 @ProfWhelan #EFAD2018
Whorwell et al, Am J Gastro 2006;101:1581-1590 Point of interest Reduction in symptom appeared to continue for 2 weeks after the end of treatment
Agrawal et al, Alim Pharm Ther 2009; 29, 104 114 Females with IBS Constipation B. lactis DN 173 010
Sissons et al, Alim Pharm Ther 2014; 40: 51-62.
Prebiotics A substrate that is selectively utilised by host micro organisms conferring a health benefit ISAPP
Prebiotics: meta-analysis of RCTs in IBS Bridgette Wilson
Prebiotics: meta-analysis of RCTs in IBS Abdominal pain, low dose Abdominal pain, high dose Flatulence, low dose Flatulence, high dose
Silk et al, Alim Pharm Ther 2009; 29, 508 518 Points of interest (1) Improvement in bloating in low dose GOS, worsening in high dose GOS (2) Limitations (high drop outs) (3) GOS (Bimuno) is not the same chemical structure as GOS in food and therefore may have different fermentation characteristics
Fermentable Oligosaccharides (fructans and α galacto oligosaccharides) Disaccharides (lactose) Monosaccharides (fructose) And Polyols (sorbitol, mannitol, xylitol etc)
Staudacher & Whelan, Gut, 2017; 66: 1517 1527 @ProfWhelan #EFAD2018
What happens during the low FODMAP diet? FODMAP restriction 4 8 weeks FODMAP reintroduction 6 10 weeks FODMAP personalisation FODMAP intake FODMAP tolerance threshold Gut symptoms Whelan et al, J Hum Nutr Diet, 2018; 31: 239 255 @ProfWhelan #EFAD2018
Low FODMAP diet advice Identifying suitable foods www.kcl.ac.uk/fodmaps www.foodmaestro.me/fodmap app @ProfWhelan #EFAD2018
Low FODMAP diet: ACG meta-analysis 7 RCTs, 397 participants Low FODMAP diet results in lower global IBS symptoms compared with control RR = 0.69 (0.54 to 0.88) Dionne, Am J Gastro 2018; 29: 549 75
Evidence for the low FODMAP diet in IBS: Staudacher and Whelan, Gut 2017; 66: 1517-1527 Number of Responders Reference Comparators Comparator FODMAP Usual diet Staudacher 2012 J Nutr 23% 68% Typical diet Halmos 2014 Gastro 70% High FODMAP diet McIntosh 2016 Gut 21% 72% Placebo diet Staudacher 2017 Gastro 38% 42% 57% 73% Active intervention NICE NICE NICE Hypnotherapy Staudacher 2011 JHum Nut D Bohn 2015, Gastro Eswaran, 2016, Am J Gastro Peters 2016, Alim Pharm Ther 39% 46% 41% 23% 72% 76% 50% 52% 51% 71%
Evidence for the low FODMAP diet in IBS: Staudacher and Whelan, Gut 2017; 66: 1517-1527 Number of Responders Reference Comparators Comparator FODMAP Usual diet Staudacher 2012 J Nutr 23% 68% Typical diet Halmos 2014 Gastro 70% High FODMAP diet McIntosh 2016 Gut 21% 72% Placebo diet Staudacher 2017 Gastro 38% 42% 57% 73% Active intervention NICE NICE NICE Hypnotherapy Staudacher 2011 JHum Nut D Bohn 2015, Gastro Eswaran, 2016, Am J Gastro Peters 2016, Alim Pharm Ther 39% 46% 41% 23% 72% 76% 50% 52% 51% 71%
Low FODMAP dietary advice vs usual diet: RCT Improves symptoms and normalises stool output Global symptom question Do you have adequate relief of your IBS symptoms? Controls 23% FODMAP 68% P = 0.003 Staudacher et al, J Nutrition 2012; 142: 1510 8
Low FODMAP diet impacts microbiome Staudacher et al, J Nutrition 2012; 142: 1510 8 Halmos et al, Gut, 2015; 64: 93 100
Evidence for the low FODMAP diet in IBS: Staudacher and Whelan, Gut 2017; 66: 1517-1527 Number of Responders Reference Comparators Comparator FODMAP Usual diet Staudacher 2012 J Nutr 23% 68% Typical diet Halmos 2014 Gastro 70% High FODMAP diet McIntosh 2016 Gut 21% 72% Placebo diet Staudacher 2017 Gastro 38% 42% 57% 73% Active intervention NICE NICE NICE Hypnotherapy Staudacher 2011 JHum Nut D Bohn 2015, Gastro Eswaran, 2016, Am J Gastro Peters 2016, Alim Pharm Ther 39% 46% 41% 23% 72% 76% 50% 52% 51% 71%
Low FODMAP diet AND... Probiotics Fermentable Oligosaccharides Disaccharides Monosaccharides And Polyols
Low FODMAP diet compared with placebo diet, plus probiotics Dr Heidi Staudacher Supplement 2 x 2 factorial RCT Low FODMAP diet advice Dietary advice Placebo sham diet advice Probiotic Both Probiotic only Placebo Low FODMAP only Neither Staudacher et al, Gastroenterology, 2017; 153: 936 947
Low FODMAP diet compared with placebo diet, plus probiotics Staudacher et al, Gastroenterology, 2017; 153: 936 947
Low FODMAP diet compared with placebo diet, plus probiotics Staudacher et al, Gastroenterology, 2017; 153: 936 947
Predicting who will respond based upon volatile organic compounds in stool at baseline Dr Megan Rossi King s College London Prof Chris Probert University of Liverpool Rossi et al, Clin Gastro Hepatol 2018; 16: 385 391
Predicting who will respond based upon volatile organic compounds in stool at baseline 15 features able to predict response to LFD with 97% accuracy 10 features able to predict response to probiotic with 88% accuracy Rossi et al, Clin Gastro Hepatol 2018; 16: 385 391
British Dietetic Association guidelines 1 st line advice (food pattern, fibre, fluid, fat, chilli, probiotics) 2 nd line advice (low FODMAP diet) McKenzie, J Hum Nutr Diet 2016; 29: 549 75
Modifying the gut microbiome in IBS Gut microbiome is altered in some people with IBS and may play in role in its pathogenesis, including hypersensitivity to colonic gas Many RCTs show some strains of probiotics have an impact on some symptoms in some people with IBS Limited trials of prebiotics in IBS RCTs demonstrate low FODMAP diet reduces colonic gas and improves symptoms in IBS, but impacts the microbiome, presumably due to reduced prebiotic intake (fructans, GOS) Approaches to modifying this require investigation: Probiotics?? (Staudacher), Prebiotics?? (Wilson) Nutritional Sciences King s College London
Dr Heidi Staudacher Dr Megan Rossi Dr Eirini Dimidi Bridgette Wilson Dr Miranda Lomer Dr Peter Irving Prof Chris Probert (University of Liverpool) Dr Raphael Aggio (University of Liverpool) @ProfWhelan #EFAD2018