May 6, 2015
The Human Microbiome
Kerry Jo Lee
Medical Officer, Division of Gastroenterology and Inborn Error Products,
Food and Drug Administration
The Human Microbiome
Kerry Jo Lee
Medical Officer, Division of Gastroenterology and Inborn Error Products,
Food and Drug Administration
Introducer, BF Graham, and Speaker, Kerry Jo Lee
Minutes of the 30th Meeting of the 73rd Year
The 30th meeting of the 73rd year of Old Guard of Princeton was called to order by President Owen Leech at the Princeton Public Library at 10:15 AM. 87 people were in attendance.
The Invocation was led by Julia Denny.
The minutes of the April 29th meeting were read by Julia Coale.
BF Graham introduced her guests, Harold Shapiro and Eric Glynn.
Claire Jacobus, representing the nominating committee, announced the slate of officers and committee chairs for the 2015-2016 term.
President: Owen Leach
Vice-President: Charles Rojer
Secretary: Julia Coale
Treasurer: Charles Clark
Assistant Treasurer: Miquelon (Micky) Weyeneth
Recording Secretary: John Riganati
Audio-Visual: David Fulmer
Historian: Diana Crane
Hospitality: Tony Glockler
Membership: Arthur Eschenlauer
Nominating: Claire Jacobus
Program: Stephen Schreiber
University Relations: Jothan Johnson
Venues: Ralph Widner
Website: Roland Miller
Assistant Website: Bruno Walmsley
Ex Officio: Ruth Miller
Proposed changes to the bylaws will be sent to members. They will be entered into the record at the May 13 meeting and voted on at the May 20th meeting.
Today’s speaker, Dr. Kerry Jo Lee, was introduced by BFG Graham.
The topic of Dr. Lee’s talk is the Human Biome.
Dr Lee is currently a Medical Officer in the Division of Gastroenterology and Inborn Error Products at the Food and Drug Administration, Washington, DC.
She attended Princeton University where she graduated with a degree in ecology and evolutionary biology. She obtained her MD and microbiology degrees from NYU. Dr. Lee received additional training at the Los Angeles Children’s Hospital and Columbia University. Following her graduate work, Dr. Lee was appointed to President Clinton’s National Bioethics Advisory Commission. Dr Lee is Board Certified in Pediatrics, Gastroenterology and Hepatology. She has pursued research in evolutionary biology with a special interest in the microbiome of the great apes. Dr. Lee leads the FDA’s research into biomarkers of inflammatory diseases and consults with regulatory agencies many foreign countries.
Dr. Lee entitled her talk, “A Macro view of the Microbiome.”
The microbiome is defined as all the microbes that make up our gut. These not only include bacteria, but also viruses, fungi and phages.
There are 100 Trillion bacteria that live in our gut; This represents 10 times the number of “human” cells in our bodies with 100-150x as many genes as there are in the human genome. WE ARE MORE BACTERIA THAN WE ARE HUMAN. These organisms reside in all parts of our digestive system and are different species depending on the PH of the organ and, in increasing numbers from the mouth to the colon.
The functions of gut microbiome are;
1, The production of antimicrobial factors
2. Barrier Protection (increasing mucous production in the gut that prevents ingestion of pathogens
3. Education our immune system.
The organisms of the biome “talk” directly to receptors on gut associated lymphoid tissue (GALT) to show the immune system what is good or bad. They also communicate indirectly with each other by the production of short chain fatty acids that induce various immune globulins such as Iga that fights disease and induces production of bile acids. They also communicate directly with each other in disease states by a technique called “CORM Sensing.” The lactobacillus, a normal bacteria in the gut, and also found in probiotics, uses corm sensing to kill pathogens; they also produce an antibiotic substance called “Reuterin” that kills pathogenic E. Coli.
A recent study showed that people have three different Enterotypes (bacterial biomes) depending on their diet.
1. Bacteroides: highly associated with animal protein/saturated fats, suggesting meat consumption (Western diet}
2. Prevotella: high values for carbohydrates/simple sugars, indicating association with a carbohydrate based diet (agrarian/vegetarians)
3. Ruminococcus: rare, not identified with a particular diet
Whatever Enterotype one has, the functions remain the same. Therefore, at this time, one cannot relate normal biomes to predict disease states.
What affects the Microbiome?
1. Mechanism of birth (C-section vs. Vaginal)
2. Placenta
3. From birth to age 3 humans have a rapid increase in the number of organisms in their biome. After age three, the biome remains stable throughout adulthood.
4. Nutrition: breast fed vs. formula, type of solids
5. Drugs: esp. antibiotics
6. stress and hygiene
In summary: a healthy microbiome is very complex and stable. It can protect against a variety of pathogens, train the immune system, help to produce vitamins, energy and fatty acids. If it maintains a normal growth from age 0-3, it has the potential to be protective throughout adulthood until old age when the numbers of bacteria in the gut tend to decline.
When the microbiome is out of sync (dysbiotic), it can cause inflammation, stress the cellular pathways of the body and allow the production more pathogens.
Implications.
1. Gut-Brain Axis
Enteric Nervous System
A. The gut has 5x more neurons than in the spine
B. It is the reservoir for 90% of the body’s Serotonin
C. It is the reservoir for 50% of the body’s Dopamine
D. Communication with the brain is via the vagal nerve.
E. Anxiety: If one has chronic anxiety, their microbiome can become dysbiotic. An area most likely to respond to probiotics. Studies have shown that Germ free mice have exaggerated stress responses (swim test). If the mice are recolonized with normal gut bacteria, their stress response normalizes except in vagotomized mice where the connection between the gut and brain has been severed.
F. Conlusions: A good microbiome is necessary for fighting disease. It is necessary for good neurodevelopment.
2. The Microbiome and Nutrition:
Microbiomes in children differ markedly in those who were fed mostly meat(Europe) and those who were fed mostly grains/vegetables(Africa). The African children had a much richer biome than those in Europe. These richer (more diverse) microbiomes were associated with healthier children.
Short term dietary changes have not been shown to affect ones basic microbiome.
Fad diets may cause one to lose weight but the person’s microbiome has not changed, so when he/she stops dieting, the obesity returns.
3. The Microbiome and obesity:
People who are obese have very different microbiomes.
A. Decreases in bacterial diversity inc. Bacteriodes.
B. Obese mice have been shown to harvest more energy than normal mice while being fed the same diet.
The Microbiome in Other Diseases:
The conditions include, cardio-vascular disease, diabetes, inflammatory bowel disease, and cancers of the stomach, colon and liver.
Studies have shown that heart disease is NOT directly associated with eating meat. However, red meat, which has L-carnitine as a component and lobsters/egg yolks that have choline as a component. L-carnitine and choline are transformed by gut bacteria into TMAO(trimethyl amine N Oxide) that produces atherosclerosis. Vegetarians do not have significant gut bacteria to produce high levels of TMAO.
Irritable bowel syndrome is found in 15-20% of the population. Studies have shown that people receiving antibiotics responded better than controls and their responses continued for a period of time after the antibiotics were discontinued.
Inflammatory bowel disease (Crohn’s disease and Ulcerative colitis) These people have decreased richness (diversity) of their microbiomes and an increase in disruptive species.
Treatment of conditions associated with disruptions of the microbiome.
Diet
Antibiotics
Fecal transplant is not a new therapy. It has been used, on and off, for the past 50 years in patients who have not responded to diet and/or antibiotics. However, it has gotten more attention since understanding their biomes has become available. Studies in patients with C. Diff. infections show significant improvement (94%) and less mortality with stool transplants.
Some Remaining Challenges to microbiome research.
Dr. Lee’s take home message was, “Your mother was right, EAT YOUR VEGETABLES!”
Questions were asked about the effect of antibiotics in food on the biome, the treatment of ADHD with probiotics, effect exercise on the microbiome, anorexia nervosa and the biome, techniques of microbiome analysis, impact of sugar on the microbiome, effect of frequent antibiotic usage in children in the development of a rich microbiome, what is the function of the FDA, hunger effects on the microbiome, effect of alcohol on the microbiome, food allergy and the biome, autism and the biome, public policy changes, “What do you eat”?
The meeting was adjourned at 11:30 AM
Respectively submitted,
M. David Atkin, M.D.
NYT article “Invite some germs to dinner,” 5/10/15 refers to too much sterilizing of our food may cause faulty development of our biomes and it may be the cause of increased allergy and autoimmune diseases.
The Invocation was led by Julia Denny.
The minutes of the April 29th meeting were read by Julia Coale.
BF Graham introduced her guests, Harold Shapiro and Eric Glynn.
Claire Jacobus, representing the nominating committee, announced the slate of officers and committee chairs for the 2015-2016 term.
President: Owen Leach
Vice-President: Charles Rojer
Secretary: Julia Coale
Treasurer: Charles Clark
Assistant Treasurer: Miquelon (Micky) Weyeneth
Recording Secretary: John Riganati
Audio-Visual: David Fulmer
Historian: Diana Crane
Hospitality: Tony Glockler
Membership: Arthur Eschenlauer
Nominating: Claire Jacobus
Program: Stephen Schreiber
University Relations: Jothan Johnson
Venues: Ralph Widner
Website: Roland Miller
Assistant Website: Bruno Walmsley
Ex Officio: Ruth Miller
Proposed changes to the bylaws will be sent to members. They will be entered into the record at the May 13 meeting and voted on at the May 20th meeting.
Today’s speaker, Dr. Kerry Jo Lee, was introduced by BFG Graham.
The topic of Dr. Lee’s talk is the Human Biome.
Dr Lee is currently a Medical Officer in the Division of Gastroenterology and Inborn Error Products at the Food and Drug Administration, Washington, DC.
She attended Princeton University where she graduated with a degree in ecology and evolutionary biology. She obtained her MD and microbiology degrees from NYU. Dr. Lee received additional training at the Los Angeles Children’s Hospital and Columbia University. Following her graduate work, Dr. Lee was appointed to President Clinton’s National Bioethics Advisory Commission. Dr Lee is Board Certified in Pediatrics, Gastroenterology and Hepatology. She has pursued research in evolutionary biology with a special interest in the microbiome of the great apes. Dr. Lee leads the FDA’s research into biomarkers of inflammatory diseases and consults with regulatory agencies many foreign countries.
Dr. Lee entitled her talk, “A Macro view of the Microbiome.”
The microbiome is defined as all the microbes that make up our gut. These not only include bacteria, but also viruses, fungi and phages.
There are 100 Trillion bacteria that live in our gut; This represents 10 times the number of “human” cells in our bodies with 100-150x as many genes as there are in the human genome. WE ARE MORE BACTERIA THAN WE ARE HUMAN. These organisms reside in all parts of our digestive system and are different species depending on the PH of the organ and, in increasing numbers from the mouth to the colon.
The functions of gut microbiome are;
1, The production of antimicrobial factors
2. Barrier Protection (increasing mucous production in the gut that prevents ingestion of pathogens
3. Education our immune system.
The organisms of the biome “talk” directly to receptors on gut associated lymphoid tissue (GALT) to show the immune system what is good or bad. They also communicate indirectly with each other by the production of short chain fatty acids that induce various immune globulins such as Iga that fights disease and induces production of bile acids. They also communicate directly with each other in disease states by a technique called “CORM Sensing.” The lactobacillus, a normal bacteria in the gut, and also found in probiotics, uses corm sensing to kill pathogens; they also produce an antibiotic substance called “Reuterin” that kills pathogenic E. Coli.
A recent study showed that people have three different Enterotypes (bacterial biomes) depending on their diet.
1. Bacteroides: highly associated with animal protein/saturated fats, suggesting meat consumption (Western diet}
2. Prevotella: high values for carbohydrates/simple sugars, indicating association with a carbohydrate based diet (agrarian/vegetarians)
3. Ruminococcus: rare, not identified with a particular diet
Whatever Enterotype one has, the functions remain the same. Therefore, at this time, one cannot relate normal biomes to predict disease states.
What affects the Microbiome?
1. Mechanism of birth (C-section vs. Vaginal)
2. Placenta
3. From birth to age 3 humans have a rapid increase in the number of organisms in their biome. After age three, the biome remains stable throughout adulthood.
4. Nutrition: breast fed vs. formula, type of solids
5. Drugs: esp. antibiotics
6. stress and hygiene
In summary: a healthy microbiome is very complex and stable. It can protect against a variety of pathogens, train the immune system, help to produce vitamins, energy and fatty acids. If it maintains a normal growth from age 0-3, it has the potential to be protective throughout adulthood until old age when the numbers of bacteria in the gut tend to decline.
When the microbiome is out of sync (dysbiotic), it can cause inflammation, stress the cellular pathways of the body and allow the production more pathogens.
Implications.
1. Gut-Brain Axis
Enteric Nervous System
A. The gut has 5x more neurons than in the spine
B. It is the reservoir for 90% of the body’s Serotonin
C. It is the reservoir for 50% of the body’s Dopamine
D. Communication with the brain is via the vagal nerve.
E. Anxiety: If one has chronic anxiety, their microbiome can become dysbiotic. An area most likely to respond to probiotics. Studies have shown that Germ free mice have exaggerated stress responses (swim test). If the mice are recolonized with normal gut bacteria, their stress response normalizes except in vagotomized mice where the connection between the gut and brain has been severed.
F. Conlusions: A good microbiome is necessary for fighting disease. It is necessary for good neurodevelopment.
2. The Microbiome and Nutrition:
Microbiomes in children differ markedly in those who were fed mostly meat(Europe) and those who were fed mostly grains/vegetables(Africa). The African children had a much richer biome than those in Europe. These richer (more diverse) microbiomes were associated with healthier children.
Short term dietary changes have not been shown to affect ones basic microbiome.
Fad diets may cause one to lose weight but the person’s microbiome has not changed, so when he/she stops dieting, the obesity returns.
3. The Microbiome and obesity:
People who are obese have very different microbiomes.
A. Decreases in bacterial diversity inc. Bacteriodes.
B. Obese mice have been shown to harvest more energy than normal mice while being fed the same diet.
The Microbiome in Other Diseases:
The conditions include, cardio-vascular disease, diabetes, inflammatory bowel disease, and cancers of the stomach, colon and liver.
Studies have shown that heart disease is NOT directly associated with eating meat. However, red meat, which has L-carnitine as a component and lobsters/egg yolks that have choline as a component. L-carnitine and choline are transformed by gut bacteria into TMAO(trimethyl amine N Oxide) that produces atherosclerosis. Vegetarians do not have significant gut bacteria to produce high levels of TMAO.
Irritable bowel syndrome is found in 15-20% of the population. Studies have shown that people receiving antibiotics responded better than controls and their responses continued for a period of time after the antibiotics were discontinued.
Inflammatory bowel disease (Crohn’s disease and Ulcerative colitis) These people have decreased richness (diversity) of their microbiomes and an increase in disruptive species.
Treatment of conditions associated with disruptions of the microbiome.
Diet
Antibiotics
Fecal transplant is not a new therapy. It has been used, on and off, for the past 50 years in patients who have not responded to diet and/or antibiotics. However, it has gotten more attention since understanding their biomes has become available. Studies in patients with C. Diff. infections show significant improvement (94%) and less mortality with stool transplants.
Some Remaining Challenges to microbiome research.
- Underestimation of significance of various bacteria
- Lack of Positive and negative controls in studies.
- Finding stool donors!
Dr. Lee’s take home message was, “Your mother was right, EAT YOUR VEGETABLES!”
Questions were asked about the effect of antibiotics in food on the biome, the treatment of ADHD with probiotics, effect exercise on the microbiome, anorexia nervosa and the biome, techniques of microbiome analysis, impact of sugar on the microbiome, effect of frequent antibiotic usage in children in the development of a rich microbiome, what is the function of the FDA, hunger effects on the microbiome, effect of alcohol on the microbiome, food allergy and the biome, autism and the biome, public policy changes, “What do you eat”?
The meeting was adjourned at 11:30 AM
Respectively submitted,
M. David Atkin, M.D.
NYT article “Invite some germs to dinner,” 5/10/15 refers to too much sterilizing of our food may cause faulty development of our biomes and it may be the cause of increased allergy and autoimmune diseases.