Understanding The Gut Microbiome
The Gut Microbiota. There are 10-100 trillion microbes that reside in our gastrointestinal tract, representing thousands of species. Understanding The Gut Microbiome
The gut microbiota is a control center for multiple aspects of our biology including our immune status, metabolism, and neurobiology.
The Gut Microbiota
There are 10-100 trillion microbes that reside in our gastrointestinal tract, representing thousands of species. The gut microbiota is a control center for multiple aspects of our biology including our immune status, metabolism, and neurobiology. Many of the metabolic activities and developmental signals that the microbiota deploys are complementary to our own, affirming that humans are composite organisms consisting of microbial and human parts.
Microbiota composition varies considerably between individuals, and factors like variation in host genotype and diet impact the community. Changes in our microbial communities differentially influence aspects of host biology (e.g., immune function) and likely explain aspects of variation within and between human populations (e.g., predisposition to disease). The plasticity of the microbiota suggests that it may be a viable therapeutic target, and necessitates the pursuit of a fundamental understanding of how extrinsic and intrinsic factors alter its composition, function, and interaction with the host.
How Many Bacteria Vs Human Cells Are In The Body?
When people ask me what the microbiome is, part of my answer usually includes the fact that there are 10 times as many bacteria in the body as human cells in the body. Unfortunately, I may no longer be able to use that statistic. A recent study out of the Weizmann Institute in Israel states that the number of bacteria may actually be very similar to the number of human cells in the body.
The authors of the study found that the 10:1 ratio of bacterial to human cells goes back to a 1977 study by Dwayne Savage and an earlier 1972 paper estimating the number of bacterial cells in the human body. The Weizmann scientists redid the estimate and found that there were about 39 trillion bacterial cells in the body. They also estimated the number of human cells in the body, about 84% of which are red blood cells, finding there to be about 30 trillion human cells in the body.
While this results in about 1.3 bacterial cell per human cell, the numbers may vary significantly from person to person and could change significantly with each defecation. They estimate that the range of bacterial cells goes from about 30 to 50 trillion in each individual. Women may also have a higher ratio of bacterial cells than human cells because they have fewer human cells, specifically red blood cells.
A team of biologists led by Ron Milo from the Weizmann Institute of Science set out to review all the available literature on the microbe populations that live inside us.
They found that for a man between 20 and 30 years old, with a weight of about 70 kg (154 pounds) and a height of 170 cm (about 5’7) – they call him the ‘reference man’ – there would be about 39 trillion bacterial cells living among 30 trillion human cells.
This gives us a ratio of about 1.3:1 – almost equal parts human to microbe.
A little bit about the Sonnenburgs…
Dr. Justin Sonnenburg is an associate professor of microbiology and immunology at Stanford and Dr. Erica Sonnenburg is a senior research scientist in the Sonnenburg lab.
Erica and Justin both research the interaction between diet and the 100 trillion or so bacteria in the gut (specifically the colon) and how this impacts the health of the host (which, in this case, is a laboratory research mouse).
In addition to their work in the lab pushing the boundaries of human knowledge on the gut, Erica & Justin have also published a book entitled The Good Gut: Taking Control of Your Weight, Your Mood, and Your Long-term Health.
In this article we discuss…
How our Western diets compare to those of traditional societies (like hunter-gatherers in Tanzania) and just how far we are from the upper limits of normal.
To reach the upper ends of normal we’d need to increase our fiber by 10 to 13-fold. Ouch! (15g/day on average versus up to around 200g/day)
How this lack of fiber in the typical American diet actually starves good bacteria of their food, and how this has an effect not only on the immune system and autoimmune diseases but also results in the breakdown of the gut barrier, which leads to widespread inflammation and inflammatory diseases.
The pivotal role fiber plays in fueling good bacteria in the gut that act like “miniature drug factories” which produce compounds that regulate the immune system by including increasing the number of T regulatory cells, which are specialized types of immune cells that keep the immune system in check and prevent autoimmune responses.
How the compounds produced by bacteria also increase other types of blood cells in the body in a process known as hematopoiesis.
Lastly, in this podcast (see below) , Dr. Erica Sonnenburg talks about how C-sections have a negative effect on the infant’s gut due to the lack of exposure to bacteria present in the mother’s vaginal canal, and how the use of formula deprives the infant not only from the good bacteria present in Mom’s gut but also from special carbohydrates in breast milk (human milk oligosaccharides) which are specialized just for encouraging the right kind of commensal gut flora while discouraging the pathogenic variety.
Gut Bacteria Affects Brain Health, Mouse Study Shows
A growing pile of evidence indicates that the tens of trillions of microbes that normally live in our intestines — the so-called gut microbiome — have far-reaching effects on how our bodies function. Members of this microbial community produce vitamins, help us digest food, prevent the overgrowth of harmful bacteria and regulate the immune system, among other benefits.
Now, a new study suggests that the gut microbiome also plays a key role in the health of our brains, according to researchers from Washington University School of Medicine in St. Louis.
The study, in mice, found that gut bacteria — partly by producing compounds such as short chain fatty acids — affect the behavior of immune cells throughout the body, including ones in the brain that can damage brain tissue and exacerbate neurodegeneration in conditions such as Alzheimer’s disease.
The findings, published Jan. 13 in the journal Science, open up the possibility of reshaping the gut microbiome as a way to prevent or treat neurodegeneration.
“We gave young mice antibiotics for just a week, and we saw a permanent change in their gut microbiomes, their immune responses, and how much neurodegeneration related to a protein called tau they experienced with age,” said senior author David M. Holtzman, MD, the Barbara Burton and Reuben M. Morriss III Distinguished Professor of Neurology. “What’s exciting is that manipulating the gut microbiome could be a way to have an effect on the brain without putting anything directly into the brain.”
Evidence is accumulating that the gut microbiomes in people with Alzheimer’s disease can differ from those of healthy people. But it isn’t clear whether these differences are the cause or the result of the disease — or both — and what effect altering the microbiome might have on the course of the disease.
To determine whether the gut microbiome may be playing a causal role, the researchers altered the gut microbiomes of mice predisposed to develop Alzheimer’s-like brain damage and cognitive impairment.
The mice were genetically modified to express a mutant form of the human brain protein tau, which builds up and causes damage to neurons and atrophy of their brains by 9 months of age.
They also carried a variant of the human APOE gene, a major genetic risk factor for Alzheimer’s. People with one copy of the APOE4 variant are three to four times more likely to develop the disease than people with the more common APOE3variant.
Along with Holtzman, the research team included gut microbiome expert and co-author Jeffrey I. Gordon, MD, the Dr. Robert J. Glaser Distinguished University Professor and director of the Edison Family Center for Genome Sciences & Systems Biology; first author Dong-Oh Seo, PhD, an instructor in neurology; and co-author Sangram S. Sisodia, PhD, a professor of neurobiology at the University of Chicago.
When such genetically modified mice were raised under sterile conditions from birth, they did not acquire gut microbiomes, and their brains showed much less damage at 40 weeks of age than the brains of mice harboring normal mouse microbiomes.
When such mice were raised under normal, nonsterile conditions, they developed normal microbiomes. A course of antibiotics at 2 weeks of age, however, permanently changed the composition of bacteria in their microbiomes. For male mice, it also reduced the amount of brain damage evident at 40 weeks of age.
The protective effects of the microbiome shifts were more pronounced in male mice carrying the APOE3 variant than in those with the high-risk APOE4variant, possibly because the deleterious effects of APOE4canceled out some of the protection, the researchers said. Antibiotic treatment had no significant effect on neurodegeneration in female mice.
“We already know, from studies of brain tumors, normal brain development and related topics, that immune cells in male and female brains respond very differently to stimuli,” Holtzman said. “So it’s not terribly surprising that when we manipulated the microbiome we saw a sex difference in response, although it is hard to say what exactly this means for men and women living with Alzheimer’s disease and related disorders.”
Further experiments linked three specific short-chain fatty acids — compounds produced by certain types of gut bacteria as products of their metabolism — to neurodegeneration. All three of these fatty acids were scarce in mice with gut microbiomes altered by antibiotic treatment, and undetectable in mice without gut microbiomes.
These short-chain fatty acids appeared to trigger neurodegeneration by activating immune cells in the bloodstream, which in turn somehow activated immune cells in the brain to damage brain tissue.
When middle-aged mice without microbiomes were fed the three short-chain fatty acids, their brain immune cells became more reactive, and their brains showed more signs of tau-linked damage.
“This study may offer important insights into how the microbiome influences tau-mediated neurodegeneration, and suggests therapies that alter gut microbes may affect the onset or progression of neurodegenerative disorders,” said Linda McGavern, PhD, program director at the National Institute of Neurological Disorders and Stroke (NINDS), which provided some of the funding for the study.
The findings suggest a new approach to preventing and treating neurodegenerative diseases by modifying the gut microbiome with antibiotics, probiotics, specialized diets or other means.
“What I want to know is, if you took mice genetically destined to develop neurodegenerative disease, and you manipulated the microbiome just before the animals start showing signs of damage, could you slow or prevent neurodegeneration?” Holtzman asked.
“That would be the equivalent of starting treatment in a person in late middle age who is still cognitively normal but on the verge of developing impairments.
If we could start a treatment in these types of genetically sensitized adult animal models before neurodegeneration first becomes apparent, and show that it worked, that could be the kind of thing we could test in people.”
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Perciavalle Patrick has a Ph.D. in biomedical science from the University of Tennessee Health Science Center, Memphis TN and St. Jude Children’s Research Hospital, Memphis TN. She also has a Bachelor’s of Science degree in biochemistry/chemistry from the University of California, San Diego. She has done extensive research on aging, cancer, and nutrition. She did her graduate research at St. Jude Children’s Research Hospital where she investigated the link between mitochondrial metabolism, apoptosis, and cancer. Her groundbreaking work discovered that a protein that is critical for cell survival has two distinct mitochondrial localizations with disparate functions, linking its anti-apoptotic role to a previously unrecognized role in mitochondrial respiration and maintenance of mitochondrial structure. Her dissertation findings were published in the 2012 issue of Nature Cell Biology.
Dr. Patrick trained as a postdoctoral fellow at Children’s Hospital Oakland Research Institute with Dr. Bruce Ames. She investigated the effects of micronutrient (vitamins and minerals) inadequacies on metabolism, inflammation, DNA damage, and aging and whether supplementation can reverse the damage. In addition, she also investigated the role of vitamin D in brain function, behavior, and other physiological functions and has published papers in FASEB on how vitamin D regulates serotonin synthesis and how this relates to autism and other neuropsychiatric disorders.
Dr. Patrick has also done research on aging at the Salk Institute for Biological Sciences. At the Salk, she investigated what role insulin signaling played in protein misfolding, which is commonly found in neurodegenerative diseases such as Alzheimer’s disease.
She frequently engages the public on topics including the role micronutrient deficiencies play in diseases of aging, the role of genetics in determining the effects of nutrients on a person’s health status, benefits of exposing the body to hormetic stressors, such as through exercise, fasting, sauna use or heat stress, or various forms of cold exposure, and the importance of mindfulness, stress reduction, and sleep. It is Dr. Patrick’s goal to challenge the status quo and encourage the wider public to think about health and longevity using a proactive, preventative approach.
* Vitamin D and the Omega-3 Fatty Acids Control Serotonin Synthesis and Action, Part 2: Relevance for ADHD, Bipolar, Schizophrenia, and Impulsive Behavior FASEB Journal
* Vitamin D Hormone Regulates Serotonin Synthesis. Part 1: Relevance for Autism FASEB Journal
* Requirement for Anti-Apoptotic MCL-1 in the Survival of BCR-ABL B-Lineage Acute Lymphoblastic Leukemia Blood
* Delving Deeper: MCL-1′s Contribution to Normal and Cancer Biology Trends in Cell Biology
* Anti-Apoptotic MCL-1 Localizes to the Mitochondrial Matrix and Couples Mitochondrial Fusion to Respiration Nature Cell Biology
* Ubiquitin-Independent Degradation of Anti-Apoptotic MCL-1 Molecular and Cellular Biology
* Opposing Activities Protect Against Age-Onset Proteotoxicity Science
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