1. Probiotics and Pouchitis What it all about?
Dr. Matt. Johnson

2. History of the IAPouch
1944 Proctocolectomy + Ileostomy (Strauss + Strauss)
1969 Intra-Abdominal Ileal Reservoir (Kock)
1978 Restorative Proctocolectomy
(Parks + Nicholls)
1987 J-Pouch Modification
(Nicholls)

5. A Normal Pouch

6. Pathological changes within a normal Healthy Pouch
6/52
plasma cell infiltration
Later = lymphocyte infiltration
6/12
Villous atrophy
>6/12
“Normal adaptation” to “colonic type mucosa”
Tendency to colonic metaplasia

7. Pouch Flora Flora (10x as much bacteria as cells in the body)
55% of stool = bacteria
Bacteria feed on undigested food by a process of fermentation
Prox jejunum (cfu/g of dry weight stool)
Ileum
Pouch
Caecum

8. Pouch Flora The proportion of anaerobes increases distally
Ileum = 1:1 (Anaerobe : aerobe)
Caecum = 1000:1
Ileal Pouch = 100:1
Colonic type flora (bacterioides, bifidobacteria)

9. Pouchitis Symptoms A) Post Op Stool Frequency B) Rectal Bleeding
C) Faecal Urgency* +/- Cramps
D) Fever (unusual)
* usually due to inflammation at the distal/efferent limb of the pouch
There is often poor correlation between symptoms and either the endoscopic or histology appearance

10. Pouchitis

11. Aetiology of Pouchitis
Bacterial profiles are genetically determined and remain stable lifelong
Response to Antibiotics suggests a pathogenic role for bacteria
Diverting ileostomy is therapeutic in CD (recurs 6/12 post re-anastamosis)
Pouchitis =
no difference in number of bacteria (qualitative stool studies)
no difference in type of bacteria (quantitative stool studies)
hightened immunogenicity in UC patients (EGIM of IBD)
loss of tolerance to normal bacteria
No longer able to distinguish between normal and pathogenic organisms

12. Clinical Pattern After 6/12 patients fall into 3 catagories;
1) No pouchitis (45%)
2) Relapsing + Remiting Pouchitis (42%)
3) Chronic Pouchitis (13%)
> 4/52
Recurrent courses of antibiotics needed

13. Therapy for Pouchitis There appears to be a bacterial precipitant
These bacteria appear to be Metronidazole sensitive G- anaerobes
Antibiotics (Metronidazole or Ciprofloxacin)
Probiotics VSL 3 (Gionchetti 1994)
4x lactobacilli
3x bifidobacteria
1x Strep Salivarius
1x S. thermaphiles
Remission can be maintained in 92.5% at 9/12 Vs 0% in the placebo group

14. Probiotic Therapeutic Mechanisms
Increasing the acidity (increases SCFAs)
Altering the hosts immune response at the GI mucosa
Produce antibiotic like substances (bacteriocins)
Increased IgA + IL 10 (anti-inflammatory)
Decreases IFNg and TNFa (pro-inflammatory)
Induces T cell shift towards Th2 (anti-inflammatory)
May competitively inhibit adherence of potentially pathogenic bacteria
Increase intestinal mucosa production
Produce SCFAs and vitamins

15. Bowel Flora and IBD Crohn’s UC IBD Low bifidobacteria Low lactobacilli
High E.coli (in active) 1 UC
Low lactobacilli (in active) 2
IBD
High bacteriodes/toxins and E.coli (in active) 3
Giaffer M.H. et al. The assessment of faecal flora in patients with inflammatory bowel disease by a simplified bacteriological technique. Journal of Medical Microbiology 35:
Fabia R. et al. Impairment of bacterial flora in human UC and expeimental colitis in the rat. Digestion 54:
Swidsinski A. et al. Mucosal flora in inflammatory bowel disease. Gastroenterology 122: 44-54

16. Animal Studies of Probiotics in IBD
Prevention
Lactobacillus reuteri (acetic acid mice)1
VSL 3 (IL10 deficient mice)2
Treatment
Lactobacilli x2 (methotrexate mice)3
Better with oat fibre
Fabia, R et al. The effects of exogenous administration o Lactobacillus reuteri R2LC and oat fibre on acetic acid induced colitis in the rat. Scandinavian Journal of Gastroenterology 28:
Madsen, K.L et al. Probiotic bacteria enhance murine and human intestinal epithelial barrier function. Gastroenterology
Mao Y.S et al. The effects of Lacto bacillus strains and oat fibre on methotrexate induced enterocoliis in rats. Gastroenterology 111:

17. Human Studies of Probiotics in UC
UC Treament
E.coli Nissle 1917 Vs Mesalazine for 1y 1
Remission = 68% Vs 73%
Relapses = 67% Vs 73%
E.coli Nissle 1917 Vs Mesalazine for 1y 2
n= 222
Relapses = 36% Vs 33%
Rembacken B.J. et al. Non-pathogenic E.coli verses mesalazine for the treatment of UC, a randomised trial. Lancet 354:
Kruis W. et al. Maintainance of remission in UC is equally effective with E.coli Nissle 1917 as with standard mesalazine. Gastroenterology 120 Suppl. 1:A127 (Abstr. 680)

18. Human Studies of Probiotics in CD
E.coli Nissle
Reduced relapse rate
allowed decrease/cessation in steroids
Mesalazine + yeast Sacchromyces boulardii 2
for 6/12
1/16 relapsed Vs 6/16 on mesalazine alone
Malchow, Helmut A., 1997 Crohn’s disease and E.coli. Journal of Clinical Gastroenterology 25:
Guslandi M. et al. Saccharomyces boulardii in maintainance treatment of Crohn’s. Digestive Diseases and Sciences 45:

19. Probiotic Trials in Acute Pouchitis High dose of probiotics is effective in the treatment of mild pouchitis. A pilot study. Amanidini C, Gionchetti P et al. Digestive and Liver Disease 2002; 34 (Suppl. 1):A96
Abstract
Positive results
NB = Not written up into a paper ?why

20. Probiotic Trials in Chronic Pouchitis Oral bacteriotherapy as maintainance therapy in patients wih chronic pouchitis: a double blind placebo controlled trial. Giochetti P, et al. Gastroenterology 2000; 119:
40 Patients
Placebo
n = 20
6g VSL 3
n = 20
n = 20
Relapse
n = 3
n = 0
Remission
after 9/12
n = 17

21. Trials of Probiotics as Prophylaxis Prophylaxis of pouchitis onset with probiotic therapy: a double blind placebo controlled trial. Giochetti P, et al. Gastroenterology 2000; 124:
40 Patients
Placebo
n = 20
6g VSL 3
n = 20
n = 8
40%
Pouchitis
n = 2
10%
n = 12
60%
Remission
after 12/12
n = 18
90%

22. Probiotics as od Maintainance Once daily high high dose probiotic therapy maintaining remission in recurrent/refractory pouchitis. Mimura T, et al. GUT 2004; 124:
36 Patients
Placebo
n = 16
6g VSL 3
n = 20
n = 15
93%
Pouchitis
n = 2, +1
15%
n = 1 7%
Remission
after 12/12
n = 17
85%

23. What’s on Offer Name Strain Implant Uses Saccaromyces boulardii Yes
Diarrhoea
Prevention + Rx
Actimel
L.casei strain DN
Stoneyfield Yogurt
L.reiteri
Diarrhoea Rx
Arla
L.acidophilus NCFB 1748
L.rhamnosus VTT E-97800
PrimaLiv
L.rhamnosus 271
Yakult
L.casei strain Shirota
Culturelle
L.casei GG
CDT
Pro Viva
L.plantarum 299v
IBS

24. Where’s the Future Heading
Pre-biotics
“Non-Digestible Food (NDF) ingredients that beneficially effect he host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, that can improve host health” 1 {Gibson G. 1995}

25. Prebiotics NDOs = Non-Digestible Oligosaccharides 8-15g / d
Average American diet = 5g / d
Such CHO – soluble fibre
A) Encourages growth of beneficial (saccharolytic) bacteria
B) Attract harmful (proteolytic) bacteria away from mucosa (gut wall) by saturating the adhesin-CHO binding sites
Best NDO = Oligosaccharides eg in breast milk
Oligofructose increases bifido’s x10 1
particularly if low to start (Crohn’s + UC) 2
Bouhnik Y. et al. Effects of fructo-oligosaccharide indigestion on faecal bifidobacteria and selected metabolic indexes of colon carcinogenesis in healthy humans. Nutrition and Cancer 26: 21-29
Van Loo J. et al. Functional food properties of non-digestible oligosaccharide: a consensus report from the ENDO project. British Journal of Nutrition 81:

26. Prebiotics Side Effects
Flatulence + Bloating
Rx = Gradually increase fibre with time
Gradual increase in Bifidobacterium
Decrease freely available NDF
Decreases gas formed by other bacteria

27. Prebiotics and the Pouch
IBD
Lactosucrose 8.5g a day for 14/7
Increase Bifidobacteria in 7/7 with IBD
Lactulose 1 12
Increased lactobacilli
Decreased colitis in mice
Pouchitis
Inulin 24g a day for 21/7 (crossover trial) 2 12
Decreased inflammation in 19/19 pouches
Madsen L. et al. Lactobacillus species prevent colitis in IL10 gene-deficient mice. Gastroenterology 116:
Welters C. et al. Effect of dietary inulin supplementation on inflammation of pouch mucosa in patients with ileal pouch anal anastamosis. Diseases of the colon and rectum 45:

28. Natural Prebiotics Nutraceuticals = “functional foods”
Inulin / Fructo-oligosaccharides / Lactulose Transgalacto-oilgosaccharides
Chicory (boiled root = 90% inulin)
Jerusalem artichoke
Onion
Leek
Garlic
Asparagus
Banana
(cereals eg. Oatmeal)

29. Natural Prebiotics 1) Isomalto-oligosaccharides (ISO) = Starch
2) Soyo-oligosaccharides (SOS) = Soya Beans
3) Xylo-oligosaccharides (XOS) = corn cobs
4) Lactosucrose (LS) = artificial sweeteners