Eric Claassen, Immunologist Professor Erasmus Medical Center

Transcription

1 Eric Claassen, Immunologist Professor Erasmus Medical Center Professor Business Management & Entrepreneurship in Health and Life Sciences (VU Amsterdam)

2 Darmvlokken (villi) geven oppervlakte vergroting De totale oppervlakte van de uitgespreide darm komt daarmee op meer dan 300 vierkante meter Dat is een tennisveld

3 species meeste zijn onbekend Wij hebben hen geaccepteerd als inwonende commensalen old friends Mouth polymorph germs duodenum < Streptococcus ileum Streptococcus Bacteroides stomach Streptococcus jenunum Streptococcus colon Bacteroides Clostridum Streptococcus Bifidobacteria Enterobacteria

4 Bacterieen moeten aanhechten aan darm eptiheel om te koloniseren: competitie

5 suikerkatabolieten vet- en aminozuurmetabolieten koolstofdioxide melkzuur azijnzuur mierenzuur (boterzuur indirect) ethanol diactyl acetaldehyde 3-hydroxy vetzuren phenyl-melkzuur caproïnezuur 4-hydroxy-phenyl melkzuur melkzuurbacteriën waterstofperoxide bacteriocinen bacteriocine-achtige molekulen aromaten heterocyclische molekulen Reuterine Reuteri-cycline kleine peptiden cyclische di-peptiden anti-fungale-peptiden zuurstofkatabolieten eiwitachtige stoffen

6 Darmwand en gezond epitheel is een barriere

7 Afbraak van de barriere functie -> opportunisten & ontsteking

8 Lactobacilli versterken tight junctions Occludin Claudin 1

9 % Bifidobacteria of total faecal bacteria (mean ± SE) Clinical Studies: Effects of the Prebiotic GOS/FOS Mixture in Infants 4-12 Weeks Bifidogenicity Knol et al., Human milk (n = 16) Control (n=18) study start after 4 weeks after 6 weeks

10 % Bifidobacteria of total faecal bacteria (mean ± SE) Clinical Studies: Effects of the Prebiotic GOS/FOS Mixture in Infants 4-12 Weeks 80 - Bifidogenicity * # Human milk (n = 16) GOS/FOS (n=16) Control (n=18) * p<0.05, 6 wk vs. study start, # GOS/FOS vs. control Knol et al., study start after 4 weeks after 6 weeks

11 % w/w (vers) Witlof / Cichorei Knoflook 9-16 Schorseneer 4-10 Prei 3-10 Ui 2-6 Artisjok 2-6 Asperge 2-3 Tarwemeel 1-4 Haver Banaan

12 Hierarchy of evidence Science Clinical Trial paradox V A L I D I T Y Meta-analysis of RCTs Randomised controlled trial (RCT) Observational studies (case-control, cohort) Observational studies (case report, case series) Experimental studies B I A S

13 Line of no effect The forest plot LEFT LESS EFFECT RIGHT MORE EFFECT D Souza AL. et al. BMJ 2002; 324: 361-4

14 Eradication Helicobacter pylori Tong et al. Aliment Pharmacol Ther 2007;25:

15 Eradication Helicobacter pylori Effective L acidophilus Bifidobacterium L casei Tong et al. Aliment Pharmacol Ther 2007;25:

16 Duration of diarrhoea 9 RCTs, n=1714, WMD -23 h (-38 to -7) Szajewska et al. update 2010

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18 AAD incidence (%) First Overpowered study 2012: 500+ AAD Volunteer study Ouwehand et al., in press P=0.28 P=0.005 P= Placebo Low dose High dose Antibiotic-associated diarrhea (AAD) incidence by study group. Low dose colony forming units (CFU), High-dose: CFU, Placebo: microcrystalline cellulose.

19 A=strong, B=positive controlled trials but some negative studies, C= some positive but not enough for certainty

20 Recommendations for Probiotic Use or: A claims (Floch 2011) Infectious diarrhea children AAD (antibiotic associated diarrhea) Pouchitis Ulcerative Colitis (maintenance) Immune response Atopic Eczema

21 Major PMC s in preparation close to A-status Infection prevention IBD remission induction IBS; Irritable Bowel Syndrome NEC; Necrotising EnteroColitis CRC; Colorectal cancer Vaginosis & Vaginitis

22 Health Maintenance of Athletes with Supermarket Probiotics Mike Gleeson et al. School of Sport, Exercise & Health Sciences Loughborough University, UK

23 EFFECT OF A PROBIOTIC ON RESPIRATORY INFECTIONS AND SALIVA IGA DURING INTENSE MILITARY TRAINING 47 army cadets Daily 100 ml L. casei DN probiotic drink or placebo for 3 weeks training, followed by a 5-day combat course No difference in incidence of respiratory illness Significant saliva IgA decrease only in placebo group Percentage change in saliva IgA PRO PLA Before training After 3 weeks training After combat course After 1 week recovery Tiollier et al 2007 Military Med 172:

24 Healthy Shift-workers Probiotics and resistance to infections Gastro-intestinal and respiratory

25 Total Group Shift workers: On placebo : 26% reported sick (3days) Lactobacilli : 11% [p<0.01] (also 3days) on placebo : 33% reported sick Lactobacilli: none = 0% (p<0.005)

26 PI & Bleeding on Probing

27 CHALLENGES Metabolic syndrome (obesity) Malnutrition Athletes, Military, Shift-workers URTI & Respiratory Helicobacter pylori Gingivitis, Halithosis & Caries Depression, Anxiety, Stress -> anger

28 SAFETY results - Overall 300+ clinical studies analyzed participants analyzed in studies Divided over treatment and control group Duration of studies Most common AE: Gastrointestinal disorders and infections No probiotic culture proven bacteraemia

29 Children: Good safety

30 Children: Good safety

31 Preliminary conclusion In controlled setting of clinical trials, probiotics and synbiotics are safe No significant difference between AEs in treatment and control groups Slightly protective effect Frequently documented clinical effect faster gastrointestinal transit, softer stools and reduced hospitalization duration Could reduce healthcare costs Probiotic efficacy remains controversial Approx. 20% does not show any efficacy 31

32 Parallelsessie Recidiverende infecties CDI

33 Clostridium difficile infectie (CDI)

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38 Fecal Transplant Crackdown: FDA Moves To Regulate Infection-Fighting 'Stool' Treatment Summer 2013

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41 AAD incidence (%) First Overpowered study 2012: 500+ AAD Volunteer study Ouwehand et al., in press P=0.28 P=0.005 P= Placebo Low dose High dose Antibiotic-associated diarrhea (AAD) incidence by study group. Low dose colony forming units (CFU), High-dose: CFU, Placebo: microcrystalline cellulose.

42 Examples Atopic / Constitutional Eczema

43 The Africa Paradox and the hygiënehypothesis Yazdanbakhsh et al. 2002

44 Old friends trigger regulation through innate dendritic cell receptors

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