Microbiome, allergy and inflammatory diseases

Microbiome, allergy and inflammatory diseases 1. NCDs & inflammation 2. Microbiome &GI inflammatory pathologies 3. Microbiome & autoimmunity 4. Microbiome & neurophaties 5. Microbiome & NAFLD 6. Microbiome & chronic renal diseases 7. Microbiome & allergic disease 8. Conclusions

Inflammation: the secret killer

1.4 Early microbial environment is associated with low grade inflammation 1.4 1.3 Infectious exposures in infancy may have lasting effects on the regulation of inflammation in adulthood. McDade TW. Early environments and the ecology of inflammation. Proc Natl Acad Sci U S A 2012;109 (suppl 2):17281 8.

Early microbial environment, low grade inflammation & NCDs Repeated activation and deactivation of inflammation competent regulatory pathways effective turn on/off inflammation Hygienic environments less opportunities of activation and deactivation of inflammatory pathways during critical periods of immune development. proinflammatory phenotype. McDade TW. Early environments and the ecology of inflammation. Proc Natl Acad Sci U S A 2012;109(suppl 2):17281 8.

Microbiome is linked to general inflammation Costello ME. The intestinal microbiome in human disease and how it relates to arthritis and spondyloarthritis. Best Practice & Research Clinical Rheumatology 2015; 29:202 12

Diseases associated with altered microbiome Strong association, multiple studies Weaker association, few studies de Vos WM, de Vos EA. Role of the intestinal microbiome in health and disease: from correlation to causation. Nutr Rev. 2012;70 Suppl 1:S45 56

Strategies to modulate the gut microbiota West CE; in FLAME Microbiome Interest Group. The gut microbiota and inflammatory noncommunicable diseases: associations and potentials for gut microbiota therapies. J Allergy Clin Immunol 2015;135:3 13

Microbiome, allergy and inflammatory diseases 1. Inflammatory diseases 2. Microbiome &GI inflammatory pathologies 3. Microbiome & autoimmunity 4. Microbiome & neurophaties 5. Microbiome & NAFLD 6. Microbiome & chronic renal diseases 7. Microbiome & allergic disease 8. Conclusions

Probiotics & NEC VLBW infants Probiotic (B. lactis) Synbiotic (B.lactis + inulin) Prebiotic (inulin) Dilli D. The propre save study. J Pediatr 2015; 166:545 51

Probiotics & Infantile colics L reuteri DSM 17938 vs. placebo reduction in daily crying and fussing times 60 vs 102 minutes/day; P =.045 Chau K. Probiotics for infantile colic: a randomized, doubleblind, placebo controlled trial investigating Lactobacillus reuteri DSM 17938. J Pediatr 2015;166:74 8

Probiotics in CD: systematic review 14 studies in patients with Crohn's disease (CD) no significant difference in clinical outcomes To date, there is insufficient data to recommend probiotics for use in CD. Ghouri YA. Systematic review of randomized controlled trials of probiotics, prebiotics, and synbiotics in inflammatory bowel disease. Clin Exp Gastroenterol. 2014;7:473 87

Probiotics in UC: systematic review 21 studies in patients with ulcerative colitis (UC) Improved induction of remission rates Maintained remission There is evidence to support the use of probiotics for induction and maintenance of remission in UC Ghouri YA. Systematic review of rndomized controlled trials of probiotics, prebiotics, and synbiotics in inflammatory bowel disease. Clin Exp Gastroenterol 2014;7:473 87

Microbiome & Ankylosing Spondylitis AS is associated with intestinal dysbiosis: abundance of Lachnospiraceae Ruminococcaceae Rikenellaceae Porphyromonadaceae Bacteroidaceae Reduction of Veilonellaceae Prevotellaceae the AS microbial signature Costello ME. The intestinal microbiome in human disease and how it relates to arthritis and spondyloarthritis. Best Pract Res Clin Rheumatol 2015; 29:202 12

Microbiome & Psoriasis Reduction of Staphylococci and Propionibacteria in psoriasis Reduction of diversity in Ps: Coprococcus species Akkermansia Ruminococcus Microbiome a possible target for prevention & Pseudobutyrivibrio treatment of autoimmunity No studies so far Costello ME. The intestinal microbiome in human disease and how it relates to arthritis and spondyloarthritis. Best Pract Res Clin Rheumatol 2015; 29:202 12

Microbiome & mind Germfree (GF) mice response to stress normalized by Bifidobacterium infantis Anxiety like behavior associated with chronic colitis Bifidobacterium longum NCC3001 Exposition to gut microbiota early in life alter their behavior more than exposition in adult age Friedriech MJ. Unraveling the influence of gut microbes on the mind. JAMA 2015; 13(17):1699 701

Probiotics & mind Anxious mouse may adopt the less anxious behavior of the donor of a fecal transplantation With human fecal transplants proposed for intractable Clostridium difficile infections, Should human fecal donors be screened not only for pathogens but for a history of psychiatric Illness? Friedriech MJ. Unraveling the influence of gut microbes on the mind. JAMA 2015; 13(17):1699 701

Microbiome, allergy and inflammatory diseases 1. Inflammatory diseases 2. Microbiome &GI inflammatory pathologies 3. Microbiome & autoimmunity 4. Microbiome & neurophaties 5. Microbiome & metabolic disease 6. Microbiome & chronic renal diseases 7. Microbiome & allergic disease 8. Conclusions

Microbiome & obesity associated NCDs Adults with reduced gut microbial richness display: a. higher adiposity b. insulin resistance c. dyslipidemia d. a more pronounced inflammatory phenotype Obesogenic diet reduces microbiota diversity Metabolic endotoxemia Low grade inflammation West CE; in FLAME Microbiome Interest Group. The gut microbiota and inflammatory noncommunicable diseases: associations and potentials for gut microbiota therapies. J Allergy Clin Immunol. 2015;135:3 13

Probiotics & Non Alcoholic Fatty Liver Disease Nobili V. Nonalcoholic fatty liver disease: a challenge for pediatricians. JAMA Pediatr 2015;169:170 6

Probiotics, NAFLD, obesity & type 2 diabetes probiotic administration may confer beneficial effects in the prevention of obesity it may benefit other associated metabolic disorders they can impede on chronic inflammation Le Barz M. Probiotics as Complementary Treatment for Metabolic Disorders. Diabetes Metab J. 2015;39:291 303

Studies with probiotics in CKD Decreased CRP Better GI symptoms Decreased TNF α & LPS Reduced Slower urea, 11% progression The quality of intervention trials of CKD investigating this novel CKD therapy is lacking Kopp L. Probiotics and chronic kidney disease. Kidney International 2015:88:958 66

Possible ambivalent effects of probiotics in chronic kidney disease. Kopp L. Probiotics and chronic kidney disease. Kidney International 2015:88:958 66

Paucity of infectious stimuli Let them get sick!

Bacterial families in fecal samples Berni Canani R. Lactobacillus rhamnosus GG supplemented formula expands butyrateproducing bacterial strains in food allergic infants. ISME J. 2016 Mar;10:742 50

Possible mechanisms of prenatal and postnatal induction of tolerance by microbial components Pfefferle PI. Microbial influence on tolerance and opportunities for intervention with prebiotics/probiotics and bacterial lysates. J Allergy Clin Immunol 2013;131:1453 63

Mechanisms of probiotics in allergy Van Bever HC. Primary prevention of allergy: will it soon become a reality? Pediatric Allergy Immunol 2016;27:6 12

Mechanisms of prebiotics in allergy Kivit S. Regulation of intestinal immune responses through TLR activation: implications for pro and prebiotics. Front Immunol 2014; 5:60. doi: 10.33890

Studies included: direct evidence Cuello Garcia CA. Probiotics for the prevention of allergy: A systematic review and meta analysis of randomized controlled trials. J Allergy Clin Immunol. 2015 136:952 61

Studies included: indirect evidence Cuello Garcia CA. Probiotics for the prevention of allergy: A systematic review and meta analysis of randomized controlled trials. J Allergy Clin Immunol. 2015 136:952 61

Probiotics in pregnancy & eczema Cuello Garcia CA. Probiotics for the prevention of allergy: A systematic review and meta analysis of randomized controlled trials. J Allergy Clin Immunol. 2015 136:952 61

Probiotics in breastfeeding & eczema Cuello Garcia CA. Probiotics for the prevention of allergy: A systematic review and meta analysis of randomized controlled trials. J Allergy Clin Immunol. 2015 136:952 61

Probiotics in infancy & eczema Cuello Garcia CA. Probiotics for the prevention of allergy: A systematic review and meta analysis of randomized controlled trials. J Allergy Clin Immunol. 2015 136:952 61

Conclusions Supplementation of probiotics during pregnancy, in breastfeeding women and/or infants reduced the risk of eczema, including atopic eczema, in infants. Our certainty in this evidence is low: risk of bias Inconsistency imprecision of estimated effect use of bodies of indirect evidence. Supplementation of probiotics does not reduce the risk of other allergies in children but we cannot exclude such a possibility. Cuello Garcia CA. Probiotics for the prevention of allergy: A systematic review and meta analysis of randomized controlled trials. J Allergy Clin Immunol. 2015 136:952 61

Prebiotics in infancy & allergic diseases Definition: Non digestible food components that may benefit the host by selectively stimulating the growth or activity of bacteria in the colon and/or promote a balanced growth of the intestinal microbiota. Cuello Garcia CA. Prebiotics for the prevention of allergy: A systematic review and meta analysis of randomized controlled trials. submitted

Prebiotics in infancy & eczema Cuello Garcia CA. Prebiotics for the prevention of allergy: A systematic review and meta analysis of randomized controlled trials. submitted

Prebiotics in infancy & asthma/wheezing Cuello Garcia CA. Prebiotics for the prevention of allergy: A systematic review and meta analysis of randomized controlled trials. submitted

Prebiotics in infancy & food allergy Cuello Garcia CA. Prebiotics for the prevention of allergy: A systematic review and meta analysis of randomized controlled trials. submitted

Who are the high risk children? High risk for allergy in a child = a biological parent or sibling with existing or history of allergic rhinitis, asthma, eczema, food allergy. Fiocchi A, Pawankar R and the WAO / McMaster working group. GuideLines for Allergic Disease Prevention.: Probiotics. WAO Journal, 2015; 8:3, 28

Pregnancy The WAO guideline panel suggests using probiotics in pregnant women at high risk for allergy in their children Considering all critical outcomes net benefit resulting primarily from prevention of eczema Fiocchi A, Pawankar R and the WAO / McMaster working group. GuideLines for Allergic Disease Prevention.: Probiotics. WAO Journal, 2015; 8:3, 28 January 2015

Breastfeeding The WAO guideline panel suggests using probiotics in women who breastfeed infants at high risk of developing allergy Considering all critical outcomes net benefit resulting primarily from prevention of eczema Fiocchi A, Pawankar R and the WAO / McMaster working group. GuideLines for Allergic Disease Prevention.: Probiotics. WAO Journal, 2015 8 3 28 Jan ar 2015

Infants The WAO guideline panel suggests using probiotics in infants at high risk of developing allergies Considering all critical outcomes net benefit resulting primarily from prevention of eczema Fiocchi A, Pawankar R and the WAO / McMaster working group. GuideLines for Allergic Disease Prevention.: Probiotics. WAO Journal, 2015; 8:3, 28 January 2015

GLAD p prebiotics: Pregnancy The WAO guideline panel chose to provide no recommendation at this time owing to lack of experimental and observational studies in which prebiotic supplements would be used in pregnant women. Fiocchi A, Pawankar R and the WAO / McMaster working group. GuideLines for Allergic Disease Prevention: Prebiotics. WAO Journal, 2016; 9 submitted

GLAD p prebiotics: Breastfeeding The WAO guideline panel chose to provide no recommendation at this time owing to lack of experimental and observational studies in which prebiotic supplements would be used in breastfeeding mothers. Fiocchi A, Pawankar R and the WAO / McMaster working group. GuideLines for Allergic Disease Prevention: Prebiotics. WAO Journal, 2016; 9 submitted

GLAD p prebiotics: Infancy The WAO guideline panel suggests prebiotic supplementation in not exclusively breastfed infants, both at high and at low risk for developing allergy (conditional recommendation, low certainty of evidence). Do not use prebiotic supplementation in exclusively breastfed infants (conditional recommendation, low certainty of the evidence). Higher value on possible prevention of allergies and a relatively lower value on additional cost of prebiotic supplementation. Fiocchi A, Pawankar R and the WAO / McMaster working group. GuideLines for Allergic Disease Prevention: Prebiotics. WAO Journal, 2016; 9 submitted

Allergic disease & probiotics: research needs Need for rigorously designed and well executed randomized trials of probiotics in infancy Possible differences among the strains of the same species Mechanisms? Added benefit from probiotic supplementation in addition to natural probiotics? This research may have an important impact on this recommendation. Fiocchi A, Pawankar R and the WAO / McMaster working group. GuideLines for Allergic Disease Prevention: Probiotics. WAO Journal, 2015; 8:3, 28 January 2015

Allergic disease & prebiotics: research needs Effects of using prebiotics in breastfeeding mothers. Effects of using prebiotics in pregnant women. Effects of different ways of administration of prebiotics, e.g. as milk hydrolysed formula, dairy supplements, etc. Randomized trials of the different prebiotics (e.g., GOS versus FOS). Impact of sub groups in the effect (if any) of prebiotics on the prevention of allergies, such as: a. Infants at high versus low risk of allergies b. exclusively breastfed versus not exclusively breastfed c. born by caesarean section versus vaginal delivery Large observational studies for detecting rare adverse events Fiocchi A, Pawankar R and the WAO / McMaster working group. GuideLines for Allergic Disease Prevention: Prebiotics. WAO Journal, 2016; 9, submitted