Gut microbiota in IBS and its modification by diet: probiotics, prebiotics and low FODMAP diet

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1 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 #EFAD2018

2 Irritable bowel syndrome 5 10% of the UK population Significant impact on individuals, families and healthcare

3 IBS: complex, inter-related pathophysiology Collins et al, Nature Gastro Hepatol, 2014; 11:

Microbiome in IBS: Systematic review of case-control

337 Bifidobacterium SMD= 1.17 P<0.001 (I 2 =79.

001 (I 2 =28%) Faecalibacterium prausnitzii SMD= 1.

4 Microbiome in IBS: Systematic review of case-control studies (qpcr) Liu, Digest Liver Disease 2017; 49: 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

5 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:

6 Microbiome in IBS: Differences in enterotype, richness and gas Tap et al, Gastroenterology 2017; 152:

7 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

8 Role for microbiome in IBS: mechanistic Diet-induced gas production & symptoms Major et al, Gastroenterology 2017;152:

9 Evolution of diet research in IBS Dr Eirini Dimidi Dimidi et al, Curr Opin Clin Nutr 2017; 20:

10 Probiotics Live micro organisms that, when administered in adequate amounts, confer a health benefit on the host (FAO/WHO, 2002)

11 Probiotics in IBS: systematic review of systematic reviews and BDA Guidelines McKenzie, J Hum Nutr Diet 2016; 29, 576 #EFAD2018

12 Probiotics in IBS: systematic review of systematic reviews and BDA Guidelines McKenzie, J Hum Nutr Diet 2016; 29, 576 #EFAD2018

Whorwell et al, Am J Gastro 2006;101:1581-1590 Point of interest

13 Whorwell et al, Am J Gastro 2006;101: Point of interest Reduction in symptom appeared to continue for 2 weeks after the end of treatment

14 Agrawal et al, Alim Pharm Ther 2009; 29, Females with IBS Constipation B. lactis DN

15 Sissons et al, Alim Pharm Ther 2014; 40:

16 Prebiotics A substrate that is selectively utilised by host micro organisms conferring a health benefit ISAPP

17 Prebiotics: meta-analysis of RCTs in IBS Bridgette Wilson

18 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

not the same chemical structure as GOS in food

19 Silk et al, Alim Pharm Ther 2009; 29, 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

20 Fermentable Oligosaccharides (fructans and α galacto oligosaccharides) Disaccharides (lactose) Monosaccharides (fructose) And Polyols (sorbitol, mannitol, xylitol etc)

21 Staudacher & Whelan, Gut, 2017; 66: 1517 #EFAD2018

22 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 #EFAD2018

23 Low FODMAP diet advice Identifying suitable foods #EFAD2018

24 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:

25 Evidence for the low FODMAP diet in IBS: Staudacher and Whelan, Gut 2017; 66: 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%

26 Evidence for the low FODMAP diet in IBS: Staudacher and Whelan, Gut 2017; 66: 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%

Do you have adequate relief of your IBS symptoms?

27 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 = Staudacher et al, J Nutrition 2012; 142:

28 Low FODMAP diet impacts microbiome Staudacher et al, J Nutrition 2012; 142: Halmos et al, Gut, 2015; 64:

29 Evidence for the low FODMAP diet in IBS: Staudacher and Whelan, Gut 2017; 66: 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%

30 Low FODMAP diet AND... Probiotics Fermentable Oligosaccharides Disaccharides Monosaccharides And Polyols

31 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:

32 Low FODMAP diet compared with placebo diet, plus probiotics Staudacher et al, Gastroenterology, 2017; 153:

33 Low FODMAP diet compared with placebo diet, plus probiotics Staudacher et al, Gastroenterology, 2017; 153:

34 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:

35 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:

36 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:

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

37 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

38 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 #EFAD2018

The long-term impact of the low-fodmap diet for management of irritable bowel syndrome. Dr Miranda Lomer RD.

The long-term impact of the low-fodmap diet for management of irritable bowel syndrome Dr Miranda Lomer RD Email: miranda.lomer@kcl.ac.uk What is IBS - ROME IV Criteria A functional bowel disorder in which