Pediatric Gastroenterology Dysbiosis and its impact on health
Pediatric Gastroenterology Dysbiosis and its impact on health Dr. Shrish Bhatnagar Associate Prof. ( Pediatric Gastroenterologist) Eras Lucknow Medical College and Hospital Vivekananda Polyclinic & Institute of M. Sciences, Lucknow. drshrishbhatnagar@gmail. com
Dedication JNMC SGPGIMS Late Dr S K BHATNAGAR
Gut Microbiota- Who is there • All mucosa are colonised with bacteria • The intestine is a preferred site – over 70% of all bacteria are found in the colon – large organ & rich in nutrients • Longitudinal: bacteria increase in number and composition from proximal to distal GI tract
Gut Microbiota: Where are they? • Latitudinal: bacterial composition also differs between lumen, mucus, and attached to epithelium. Epithelium Mucus Layer Intestinal Lumen Feces
Gut Microbiota: Where do they come from? • Initial exposure occurs during birth and is heavily influenced by mother and environment DENTAL AMALGAM BOTTLE FEEDING EARLY BATH LSCS EARLY LIFE ANTIBIOTICS
Gut Microbiota: After 1 year
Gut Microbiota: In Health
Gut Microbiota in Health: Innate & Adaptive Immune system • Microbiota regulates intestinal immune responses primarily through the production of pathogenassociated molecular patterns (PAMPs) and metabolic by-products. • Microbiota stimulation leads to B cell switch to Ig. A, regulatory T cell induction, T cell differentiation to Th 17
Dysbiosis • Dysbiosis : Alteration of the microbiota from the normal, healthy state. A condition of microbial imbalances rather than equilibrium of “good” and “bad” microbes. B S DY IS S IO
Intestinal Dysbiosis as possible disease factor
Agents of Rebiosis Prebiotics FOS Drugs Simvastatin, FMT C Difficle Metformin, Probiotics Rifaximin GOS Folic Acid Hepatitis
Probiotics as agent of Rebiosis
Rebiosis – Proven Clinical Impact Pediatricain Perspective 1 • Acute Infectious Diarrhea 2 • Antibiotic Associated Diarrhea 3 • Inflammatory Bowel Disease 4 • Prevention of NEC 5 • Hepatic Encephalopathy
Probiotics Bring Confusion? Duration Dose Strain Cost Vs Benefit
Evolution of Probiotics 2017 ?
Probiotics in diarrhea NO ROLE OF PRODUCTS WITH COMBINATION OF PRE & PROBIOTICS
Duration Stool Frequency on d 2 Persistence >4 d Conclusion : With ORT probiotics appear safe and beneficial in acute diarrhea Duration : 5 days
Probiotic Selection Criteria Enterogermina (Bacillus clausii) WGO Criteria: Specified by genus and strain 1 It is composed of four antibiotic-resistant strains, OC, NR, T, and SIN 2 WGO Criteria: Alive 1 Yes WGO Criteria: Shown to be efficacious in controlled human studies 1 Yes 3, 4, 5, 6 FAO/WHO Criteria: Determination of antibiotic resistance patterns 7 Yes 2 Acid resistance: Resistant to low p. H and acids 7 Yes 8 World Gastroenterology Organisation (WGO) practice guidelines: Probiotics and prebiotics. Arab Journal of Gastroenterology; 2009; 10: 33– 42 Courvalin P. Digestive and Liver Disease; 2006; 38 Suppl. 2; S 261–S 265 Nista EC et al. Aliment Pharmacol Ther 2004; 20: 1181– 1188. Benoni G et al. Chemioterapia. October 1984; Vol. 3, No. 5: 291 -293 Puddu M et al. Pediatria Internazionale. 1980; 6: 1 -5 Gabrielli M et al. Digestive and Liver Disease Supplements; 2009; 3: 50– 53 Joint FAO/WHO Working Group Report on Drafting Guidelines for the Evaluation of Probiotics in Food; London, Ontario, Canada, April 30 and May 1, 2002 Gupta V, Garg R. Indian Journal of Medical Microbiology; 2009; 27; 3: 202 -9 Ciffo F et al. Farmaci Terapia. 1987; 4 (3): 163 -169
Quality control: Relevance of species and strain identification
Some examples from the world literature - Quality control: Out of 9 only 3 products matched the label claims
What about sporeformers? In the following slides the outcomes of a survey on 5 products commercially available in India Products Declared dose Bacillus clausii Spores suspension ( bottles of 5 ml) Product A 2 x 109 spores/ 5 ml Bacillus clausii spores (sachet 1 g) Product B 2 x 109 spore in 1 g 2 x 109 spores/ 5 ml 2 x 109 spores in 1 g Bacillus clausii spores suspension ( bottles of 5 ml) Product C 2 x 109 spores/ 5 ml Bacillus clausii spores (sachets 1 g) Product D 2 x 109 spores in 1 g Bacillus clausii spores Product E ( bottles 5 ml) 2 x 109 CFU/ 5 ml 2 x 109 spores/ 5 ml 2 x 109 spores in 1 g
Identification of bacteria Drugs DGGE results % homology Product A Bacillus cereus/ licheniformis Alcaligenes faecalis Staphilococcus/Lysinibacillus Xanthomonas/Pseudomonas Bacillus clausii Bacillus amyloliquefaciens Lysinibacillus 96 73 93 94 89 87 92 Bacillus clausii Bacillus licheniformis Acinetobacter subsp Paenibacillus subsp Geobacillus Xanthomonas/Pseudomonas Bacillus cereus/ licheniformis Staphilococcus/ Lysinibacillus 92 91 76 83 76 94 96 93 Bacillus clausii 96 Bacillus subtilis Bacillus amyloliquefaciens Bacillus clausii 99 100 89 Bacillus clausii 96 Multiple microorganisms not only within the species but also belonging to different genera were present in Product A (Liquid/Susp) & Product B (Sachet) contrary to what is Bacillus subtilis/ Bacillus 100 Product B claimed amyloliquefaciens Product C Product D Product E CAUTION
Antibiotic associated Diarrhea • Scenario 1 – A 3 year old child with h/o fever cough x 3 days…Given Amoxyclav , Cetrizine and PCM. Develops diarrhea next day…. ? • Scenario 2 AAD? – A 3 years old child admitted with LRTI ; was started on IV antibiotics , 5 th day develops diarrhea with occasional blood
Antibiotic associated Diarrhea In Pediatric Population: • Incidence : 20% (vs 40% adults) • Incubation period : 3 -10 days (vs 9 -15 d ) • Etiology : C Difficile in 30% ( adults 50%) delivered in hospitals may be colonized with symptoms. ) (Up to 67% of neonates C. difficile, but rarely show diarrheal • Risk factors: Age 1 -4 yrs; Comorbidity like IBD; Exposure to antibiotics with last 12 weeks ( Multiple; Peni; Cephlo); Current Hospitalization • Presentation : Diarrhea , Abdominal Pain Fever and Colitis • Treatment : Stop antibiotics , Metronidazole DOC (vs Vancomycin Adults) • Prevention: Judicious use of antibiotics , Probiotics
High dose (≥ 5 billion CFUs/day) is more effective than low probiotic dose (< 5 billion CFUs/day), P value = 0. 010 No statistically significant difference in the incidence of adverse events between treatment and control
Dysbiosis and IBD Clinical Implications Deeper Ulcers and Abscess Hepatic abscesses, Sepsis and Endocarditis Opportunistic Infections like CMV (x 2), C Difficle (x 3)
Rebiosis and IBD Clinical Implications Probiotics Like VSL #3 have a beneficial role induction and maintenance of remission in Ulcerative Colitis and Pouchitis However no role proven role in Crohns disease 12 weeks of 800 mg b. i. d. Rifaximin (62 % vs. 43 % placebo) has been shown to beneficial in induction and maintenance of remission in IBD Most clinicians use antibiotics and Probiotics as adjunctive therapy in IBD
• Only randomized or quasi-randomized controlled trials that enrolled pre term infants < 37 weeks gestational age or < 2500 g birth weight, or both, were considered. • Enteral supplementation of probiotics prevents severe NEC ( Stage II and More) and all cause mortality in preterm infants. • Updated review of available evidence strongly supports a change in practice. Cochrane Database of Systematic Reviews 2014, Issue 4.
Case Scenario • 6 year old healthy child presents with H/O Jaundice x 10 days , Altered sensorium for 2 days; • On examination : Coma Gr 2; Deep Icterus ; Shrunken Liver with cutaneous bleed ; INR > 3 • Diagnosis: Acute Liver Failure • Treatment – – – Fluid , Electrolyte and Blood Sugar Management as per ALF poto Positioning Prophylactic acid Suppressants Prophylactic antibiotics Vitamin K 20 % Mannitol or 3% saline for cerebral edema – Gut Cleansings ( Lactulose and Rifaximin)
Rebiosis and HE • Lactulose – Lower colonic p. H Increases Non Urease Producing Bacteria, Reduces Toxic SCFA. – Dose 1 -2 ml/kg/day to have 2 -3 acidic (<6 p. H) loose stools per day. • Rifaximin Recent Study “ Lee 2017”: Combination better than single drug – A non-selective, broad antibiotic spectrum and acts on both Gram-positive and Gram-negative bacteria – Dose in adults is 550 mg twice daily – Second Line add on therapy to lactulose • FMT
Rebiosis- Future Implications in Pediatric GI Disease Gut Allergy Cancer Prevention Rebiosis Motility Disorders Obesity NASH
1 2 3 • The Human microbiome is a dynamic community • Dysbiosis is a state of microbial imbalance • Rebiosis has a proven role in treatment of Diarrhea , IBD, Hepatic Encephalopathy Hippocrates said “ All Disease Start in Gut…” Future …. Does their Cure too?
THANK YOU
Lactobacillus GG- Let More Indian Data Flow NOT BY DGCI Difficult Reconstitution Side effect High Dose
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