9/30/2013 Us- One species- Homo Sapiens The Microbiome: 10 - PDF document

9/30/2013 • Us- One species- Homo Sapiens The Microbiome: 10 Trillion cells Your Trillion Best Friends Your Trillion Best Friends 23,000 genes , g Four main phyla- Actinobacteria Firmicutes Bacteroidetes Proteobacteria • Them- • Most bacteria are neither passive passengers or parasites • They are members of an free standing • Hundreds of species • 100 trillion bacteria community, of which we, the host, are just • 3 million genes 3 million genes one member. b • Approximately 100 phyla “Co-evolution” • Bacteria provide 10%-15% of our daily • Intestinal Bacteria produce Vitamins B2, B12, calories from plant carbohydrates which and folic acid, and bacterial genes read human enzymes cannot break down signals from the gut to in turn alter their production to satisfy the host’s needs in • Complex carbohydrate-> childhood starvation and geographical childhood, starvation, and geographical Formic, acetic, butyric acid-> location. Energy or fat • Not by accident, mother’s milk, the most energy efficient food, evolved over millions of years to contain glycans which only bacterial enzymes can break down. 1

9/30/2013 Obesity Disrupted Microbiome • Animals given antibiotics “fatten” faster, and not soley due to disease prevention • Obesity • Randomize mice to 3 groups, fat mice, mice • Malnutrition with gastric bypass, mice with sham surgery • Diabetes 1 and 2 • Take bacteria from “skinny mice” and place • Atherosclerosis in obese mice and these mice lose 25% body in obese mice and these mice lose 25% body • Asthma weight • Eczema • Take mice with sterile GI tracts- • Liver Disease -Bacteria from obese humans made • Intestinal diseases and cancer obese mice -Bacteria from thin humans made • Autism thin mice • Multiple Sclerosis Heart Disease Obesity and Malnutrition • Steve Gordon, Washington University School of Medicine- obese patients have more Jeremy Nicholson- Imperial College, London Firmicutes and less Bacteroidetes, by Urinary Formic Acid levels inversely related to blood producing enzymes that stop fat stores from pressure via action of formic acid on renal tubules being utilized absorption of sodium Largest source of formic acid in the body is from GI • 317 pairs of twins in Malawi- 317 pairs of twins in Malawi metabolism by bacteria metabolism by bacteria - 43% both well nourished Stanley Hazen- Cleveland Clinic - 7% both malnourished Mice with increased levels of atherosclerosis could have - 50% discordant their disease reduced by killing their plaque-producing microbiome and replacing with a heart-healthy bacterial Malnourished children microbiomes lacked mixture vitamin producing or carbohydrate digestion enzymes Autism Diabetes • Clostridia species produce phenols (carbolic • Morbid Obesity and Diabetes acid) which are toxic to human cells • Roux-en-Y surgery reverses type 2 diabetes • Carbolic acid is neutralized by sulphate within a month compounds • Changes microbiome which re-sets bacterial • Increased Clostridia leads to decreased • Increased Clostridia leads to decreased genomic regulation of insulin sensitivity sulphur stores • Sulphur levels affect brain development (remember sulphur antibiotics and kernicterus!) • Autistic children have genetic defect which interferes with sulphur metabolism 2

9/30/2013 Research into Action Hello NAMS- Focus: The Menopausal Vagina C. difficile infections kills over 14,000 people • Co-evolution of Bacteria and Human Genes each year in the US has developed over millions of years • Mark Mellow- Oklahoma 2012 • Evolution is focused on the reproduction of the species 76 of 77 patients cured with fecal transplant enemas • Menopause is only centuries old! • Do “Grandparents” represent an evolutionary advantage? Oral capsules of healthy bacterial to re- populate infected patients- • Answer: The menopausal vagina is in its evolutionary infancy Called “Re-Poopulate” Antibiotics Direct Alteration of Vaginal Flora by Antibiotics • Are the major reason we now live well into the menopause • Leads to: - yeast infections • But continue to have both a positive and - bacterial floral changes resulting in g g negative impact on the menopausal vagina recurrent UTI - increasing symptoms of VVA Indirect Alteration of Vaginal Flora by Antibiotics • Major source of vaginal flora in menopause is GI bacteria • Leads to: - recurrent non-albicans yeast infections - MRSA -Group A Strep - Clostridium perfrigens 3