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

9/30/2013 1

The Microbiome: Your Trillion Best Friends Your Trillion Best Friends

• Us-

One species- Homo Sapiens 10 Trillion cells 23,000 genes , g Four main phyla- Actinobacteria Firmicutes Bacteroidetes Proteobacteria

• Them-
• Hundreds of species
• 100 trillion bacteria
• 3 million genes

3 million genes

• Approximately 100 phyla
• Most bacteria are neither passive

passengers or parasites

• They are members of an free standing

community, of which we, the host, are just b

• ne member.

“Co-evolution”

• Bacteria provide 10%-15% of our daily

calories from plant carbohydrates which human enzymes cannot break down

• Complex carbohydrate->

Formic, acetic, butyric acid-> 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.

• Intestinal Bacteria produce Vitamins B2, B12,

and folic acid, and bacterial genes read signals from the gut to in turn alter their production to satisfy the host’s needs in childhood starvation and geographical childhood, starvation, and geographical location.

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Disrupted Microbiome

• Obesity
• Malnutrition
• Diabetes 1 and 2
• Atherosclerosis
• Asthma
• Eczema
• Liver Disease
• Intestinal diseases and cancer
• Autism
• Multiple Sclerosis

Obesity

• Animals given antibiotics “fatten” faster, and

not soley due to disease prevention

• Randomize mice to 3 groups, fat mice, mice

with gastric bypass, mice with sham surgery

• Take bacteria from “skinny mice” and place

in obese mice and these mice lose 25% body in obese mice and these mice lose 25% body weight

• Take mice with sterile GI tracts-
• Bacteria from obese humans made
• bese mice
• Bacteria from thin humans made

thin mice Obesity and Malnutrition

• Steve Gordon, Washington University School
• f Medicine- obese patients have more

Firmicutes and less Bacteroidetes, by producing enzymes that stop fat stores from being utilized

• 317 pairs of twins in Malawi-

317 pairs of twins in Malawi

• 43% both well nourished
• 7% both malnourished
• 50% discordant

Malnourished children microbiomes lacked vitamin producing or carbohydrate digestion enzymes

Heart Disease

Jeremy Nicholson- Imperial College, London

Urinary Formic Acid levels inversely related to blood pressure via action of formic acid on renal tubules absorption of sodium Largest source of formic acid in the body is from GI metabolism by bacteria metabolism by bacteria

Stanley Hazen- Cleveland Clinic

Mice with increased levels of atherosclerosis could have their disease reduced by killing their plaque-producing microbiome and replacing with a heart-healthy bacterial mixture

Diabetes

• Morbid Obesity and Diabetes
• Roux-en-Y surgery reverses type 2 diabetes

within a month

• Changes microbiome which re-sets bacterial

genomic regulation of insulin sensitivity

Autism

• Clostridia species produce phenols (carbolic

acid) which are toxic to human cells

• Carbolic acid is neutralized by sulphate

compounds

• Increased Clostridia leads to decreased
• Increased Clostridia leads to decreased

sulphur stores

• Sulphur levels affect brain development

(remember sulphur antibiotics and kernicterus!)

• Autistic children have genetic defect which

interferes with sulphur metabolism

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Research into Action

• C. difficile infections kills over 14,000 people

each year in the US

• Mark Mellow- Oklahoma 2012

76 of 77 patients cured with fecal transplant enemas Oral capsules of healthy bacterial to re- populate infected patients- Called “Re-Poopulate” Hello NAMS- Focus: The Menopausal Vagina

• Co-evolution of Bacteria and Human Genes

has developed over millions of years

• Evolution is focused on the reproduction of

the species

• Menopause is only centuries old!
• Do “Grandparents” represent an evolutionary

advantage?

• Answer: The menopausal vagina is in its

evolutionary infancy

Antibiotics

• Are the major reason we now live well into

the menopause

• But continue to have both a positive and

negative impact on the menopausal vagina

Direct Alteration of Vaginal Flora by Antibiotics

• Leads to:
• yeast infections
• bacterial floral changes resulting in

g g 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