prof.eric.claassen@gmail.com Eric Claassen, Immunologist Professor Erasmus Medical Center Professor Business Management & Entrepreneurship in Health and Life Sciences (VU Amsterdam)
Darmvlokken (villi) geven oppervlakte vergroting De totale oppervlakte van de uitgespreide darm komt daarmee op meer dan 300 vierkante meter Dat is een tennisveld
400-900 species meeste zijn onbekend Wij hebben hen geaccepteerd als inwonende commensalen old friends Mouth 10 5 10 7 polymorph germs duodenum < 10 4-5 Streptococcus ileum 10 3 10 7 Streptococcus Bacteroides stomach 10 2 10 3 Streptococcus jenunum 10 5 10 6 Streptococcus colon 10 9 10 11 Bacteroides Clostridum Streptococcus Bifidobacteria Enterobacteria
Bacterieen moeten aanhechten aan darm eptiheel om te koloniseren: competitie
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
Darmwand en gezond epitheel is een barriere
Afbraak van de barriere functie -> opportunisten & ontsteking
Lactobacilli versterken tight junctions Occludin Claudin 1
% Bifidobacteria of total faecal bacteria (mean ± SE) Clinical Studies: Effects of the Prebiotic GOS/FOS Mixture in Infants 4-12 Weeks 80 70 - Bifidogenicity - 60 50 40 30 Knol et al., 2002 20 10 0 Human milk (n = 16) Control (n=18) study start after 4 weeks after 6 weeks
% Bifidobacteria of total faecal bacteria (mean ± SE) Clinical Studies: Effects of the Prebiotic GOS/FOS Mixture in Infants 4-12 Weeks 80 - Bifidogenicity - 70 60 * # 50 40 30 20 10 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., 2002 0 study start after 4 weeks after 6 weeks
% w/w (vers) Witlof / Cichorei 15-20 Knoflook 9-16 Schorseneer 4-10 Prei 3-10 Ui 2-6 Artisjok 2-6 Asperge 2-3 Tarwemeel 1-4 Haver 0.5-1.5 Banaan 0.3-0.7
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
Line of no effect The forest plot LEFT LESS EFFECT RIGHT MORE EFFECT D Souza AL. et al. BMJ 2002; 324: 361-4
Eradication Helicobacter pylori Tong et al. Aliment Pharmacol Ther 2007;25:155 168
Eradication Helicobacter pylori Effective L acidophilus Bifidobacterium L casei Tong et al. Aliment Pharmacol Ther 2007;25:155 168
Duration of diarrhoea 9 RCTs, n=1714, WMD -23 h (-38 to -7) Szajewska et al. update 2010
AAD incidence (%) First Overpowered study 2012: 500+ AAD Volunteer study Ouwehand et al., in press 25 20 P=0.28 P=0.005 P=0.08 15 10 5 0 Placebo Low dose High dose Antibiotic-associated diarrhea (AAD) incidence by study group. Low dose 4.17 10 9 colony forming units (CFU), High-dose: 1.70 10 10 CFU, Placebo: microcrystalline cellulose.
A=strong, B=positive controlled trials but some negative studies, C= some positive but not enough for certainty
Recommendations for Probiotic Use or: A claims (Floch 2011) Infectious diarrhea children AAD (antibiotic associated diarrhea) Pouchitis Ulcerative Colitis (maintenance) Immune response Atopic Eczema
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
Health Maintenance of Athletes with Supermarket Probiotics Mike Gleeson et al. School of Sport, Exercise & Health Sciences Loughborough University, UK
EFFECT OF A PROBIOTIC ON RESPIRATORY INFECTIONS AND SALIVA IGA DURING INTENSE MILITARY TRAINING 47 army cadets Daily 100 ml L. casei DN-114 001 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 80 60 PRO PLA 40 20 0-20 -40 Before training After 3 weeks training After combat course After 1 week recovery Tiollier et al 2007 Military Med 172: 1006-1011 23
Healthy Shift-workers Probiotics and resistance to infections Gastro-intestinal and respiratory
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)
PI & Bleeding on Probing
CHALLENGES Metabolic syndrome (obesity) Malnutrition Athletes, Military, Shift-workers URTI & Respiratory Helicobacter pylori Gingivitis, Halithosis & Caries Depression, Anxiety, Stress -> anger
SAFETY results - Overall 300+ clinical studies analyzed 30.855 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
Children: Good safety
Children: Good safety
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
www.darmgezondheid.nl Parallelsessie Recidiverende infecties CDI prof.eric.claassen@gmail.com + 31 6 204 430 98
Clostridium difficile infectie (CDI)
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Fecal Transplant Crackdown: FDA Moves To Regulate Infection-Fighting 'Stool' Treatment Summer 2013
AAD incidence (%) First Overpowered study 2012: 500+ AAD Volunteer study Ouwehand et al., in press 25 20 P=0.28 P=0.005 P=0.08 15 10 5 0 Placebo Low dose High dose Antibiotic-associated diarrhea (AAD) incidence by study group. Low dose 4.17 10 9 colony forming units (CFU), High-dose: 1.70 10 10 CFU, Placebo: microcrystalline cellulose.
Examples Atopic / Constitutional Eczema
The Africa Paradox and the hygiënehypothesis Yazdanbakhsh et al. 2002
Old friends trigger regulation through innate dendritic cell receptors
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