Human Microbiome in state of health and illness.

Transcription

1 Human Microbiome in state of health and illness. Objectives: 1) To recognize what fuels the plaque of Century 2) To understand the interaction between microbiome and human in health and disease states(dysbiosis) 3) Impact of antibiotic and diet on facilitating dysbiosis 4) What are the solutions? By: Yazdan Mirzanejad, MD,FRCPC

2 Copyright 2017 by Sea Courses Inc All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any means graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of Sea Courses Inc. except where permitted by law. Sea Courses is not responsible for any speaker or participant s statements, materials, acts or omissions.

3 Faculty/ Presenter Disclosure Yazdan Mirzanejad, MD,FRCPC RELATIONSHIP WITH COMMERCIAL INTERESTS: -- GRANT /RESEARCH SUPPORT: SANOFI PASTEUR FOR C. DIFF VACCINE MULTI CENTERS CLINICAL TRIALS -- SPEAKERS BUREAU/ HONORARIA : MERCK, PFIZER, OPTIMER, TRITON, UBC CPD, NOVA CLINICAL SERVICES -- CONSULTING FEES : NONE -- OTHER : NONE

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6 What is wrong with this Picture? 1-R.O.S Normal Physical exam normal All Lab and imaging are normal 1-Autistic? 2-Psychosis? 3-Inborn errors of metabolism? 4-something we may find by the end of this session So stay tuned!

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11 Could you name something that.. can cause blessing and at the same time harm!

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17 The desire to ingest medicines is one of the principal features which distinguish man from the animals Osler,1920p

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20 Einstein on: Environmental Monitoring 20 Not everything that can be counted counts, and not everything that counts can be counted. (oft attributed to Albert Einstein) corollary for environmental monitoring Not everything that can be measured is worth measuring, and not everything worth measuring is

21 Diabetes in the United States Prevalence (%) '62 '66 '70 '74 '78 '82 '86 ' > 65 years years years <45years Data from the US National Health Interview Survey

22 Diabetes in the United States Prevalence 15 (%) '85 '90 ' years < 45 years Data from the US National Health Interview Survey:

23 No of persons with Physician-diagnosed Diabetes in USA by year Data from the US National Health Interview Survey: g1.htm

24 Relative Risk of Diabetes Abdominal Adiposity Is Associated With Increased Risk of Diabetes 25 P value for trend < <28 > Waist Circumference (in) Carey VJ, et al. Am J Epidemiol. 1997;145:

25 Intra-abdominal (Visceral) Fat The dangerous inner fat! Front Visceral AT Subcutaneous AT Back

26 Metabolic Syndrome: Clustering of Interconnected Metabolic Risk Factors Insulin Resistance + Hyperglycemia Obesity Hypertension Atherogenic Dyslipidemia

27 Relative Risk Metabolic Syndrome and Diabetes in Relation to CHD, CVD, and Total Mortality: U.S. Men and Women Ages *** 6 *** * *** *** ** *** *** *** *** *** *** None MetS Diabetes CVD CVD+Diabetes 0 CHD Mortality CVD Mortality Total Mortality Malik and Wong, et al., Circulation * p<.05, ** p<.01, **** p<.0001 compared to none

28 No. with Diabetes (millions) * Based on diabetes incidence (5% / year) in the 20% of persons with impaired glucose homeostasis; 300,000 diabetes deaths / year; Net increase = c.700,000 cases of diabetes / year Projections of Numbers with Diabetes* among persons aged 40-74years in USA (Millions) YEAR

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39 Why might some kids have less bacteria than others? 39

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42 Carbapenems The Big Gun ertapenem imipenem meropenem doripenem

43 43 Medical ecology Many microorganisms in our bodies are critical for our lives Goal: Promote an internal environment that enables helpful bacteria to thrive and outcompete unhelpful bacteria

44 The Microbiome: Changes in flora These flora change in response to diet and obesity of host Mice and humans have different gut flora but the two largest divisions are shared in common Bacteroidetes (Gram -) Firmicutes (Gram +) Ley, et al. PNAS. 2005, 102:

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57 Please name your body organs: Central nervous System Cardiovascular System Hepatobiliary Urogenital Reticulo endothelial System Respiratory System Musculoskeletal System What else? Microbiome eco system of the human body

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61 Stop the killing of beneficial bacteria Collateral Damage Concerns about antibiotics focus on bacterial resistance but permanent changes to our protective flora could have more serious consequences, says Martin Blaser. Nature 2011;476:393 Average child receives courses of antibiotics before age 18 Antibiotics affect our resident microbiota and may not fully recover after a course of antibiotics Overuse of antibiotics may be contributing to obesity, DM, IBD, allergies, and asthma

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68 What is transforming the organic matter into ammonium? What is transforming the N 2 gas into NO 2? Principle of ecological cycles applied to the human microbiome: Microbes process B and K vitamins into forms usable by humans. 68

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71 71 What could Microbiome mean? What kinds of microbes are in humans? Source: National Institutes of Health

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76 Conclusions: Gut flora by their genes, by-products, and metabolic activity influence our metabolism, weight, activity, immunity, health and disease. The human microbiome and the Microbiome Project: research just beginning Manipulation of gut flora may be an integral part of weight loss programs and different disease treatments in the future.

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119 Background: Impact Hospital-acquired, hospitalonset: 165,000 cases, $1.3 billion in excess costs, and 9,000 deaths annually Hospital-acquired, postdischarge (up to 4 weeks): 50,000 cases, $0.3 billion in excess costs, and 3,000 deaths annually Nursing home-onset: 263,000 cases, $2.2 billion in excess costs, and 16,500 deaths annually Campbell et al. Infect Control Hosp Epidemiol. 2009:30: ;14: Dubberke et al. Clin Infect Dis. 2008;46: Brief # Dubberke et al. Emerg Infect Dis. Elixhauser et al. HCUP Statistical

120 Rate Background: Impact Age-Adjusted Death Rate* for Enterocolitis Due to C. difficile, White Black Entire US population *Per 100,000 US standard population Year Heron et al. Natl Vital Stat Rep 2009;57(14). Available at

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123 Designing Probiotics: The Future? GASTROENTEROLOGY 2009;136:

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129 TOM Says, Antimicrobial resistance happening in every Community, health care facility and medical practices. Annually, 2 million people per year infected with in USA and die. When microbes outsmart our best antibiotics, it says the consequences are catastrophic due to overuse of antibiotics. The medicine cabinet maybe empty for patients with life threatening infections in the near future!

130 Goals of Antimicrobial Stewardship Programs Optimize Patient Safety Reduce Resistance Decrease or Control Costs

131 Making the Business Case Two absolutes Improving quality almost always improves cost Reducing cost will almost never improve quality Failure to comprehend compromises both business and clinical outcomes

132 Take Home Points Optimize dose, duration, and indications for antimicrobial therapy Assure appropriate cultures are obtained before starting antibiotics Take Home Points Consider an antibiotic time-out hours after starting antimicrobial therapy

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136 1-Autistic? 2-Psychosis? 3-Inborn errors of metabolism? 4-something we may find by the end of this session

137 Barriers to change: lack of; A) Consume Low fat/plant polysaccharides diet B) Stop overusing of antibiotics C) Encourage breastfeeding D) Avoid elective C-section E) Avoid processed food F) Avoid antibiotics fed animal meat G) Development of research on Probiotics to combine with antibiotics use when treatment is indicated H) Research and development on ancient microbiota proliferation and have it accessible for cure of DM,IBD, autoimmune diseases and finally prevention of obesity, CVD and Cancer

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