Dr. Rob Knight’s talk, Saturday, October 18, 2014, listed eleven factors that optimize the gut microbiome. These are listed at the bottom of this post in the section titled: “Can We Eat Our Way To A Healthier Microbiome? It’s Complicated,” which also happens to be the link to an interesting article in which Dr. Knight and Jeff Leach (founders of crowd sourcing project “American Gut”) discuss the microbiome diet.
But first, what follows is a synopsis of Dr. Knight’s talk (email for a more detailed pdf copy):
It is crucial to understand that researchers are just starting to find out about the profound effects of the microbiome on health and disease. Much progress has been made in the last 5 years, but many compelling questions remain unanswered. It is the recent gene sequencing technological advances that has launched new studies that are revolutionary in how we view biology. Publications of studies based on this technology only broke out in the scientific literature in 2011 and 2012 and are aimed at understanding how (and, more importantly, why) humans harbor multitudes of symbiotic bacteria. Up until now, we never knew that microbes are so involved with the process of sustaining our life as researchers now catalog microbes they’ve never before seen: they have no scientific name; they are not culture-able; they are only “seen” though DNA sequencing.
For Background: The human body is permanently colonized by microbial organisms on virtually all environmentally exposed surfaces: skin, mouth, respiratory, genitalia , and the largest colonizer, the gut.
In the GI tract, microbes outnumber host cells by 10-fold. We have 10 trillion human cells, but 100 trillium microbial cells. Thus, we are 90% bacteria, or 10% human, on a cellular level. On a gene level, we have only 20,000 human genes. But, our microbial genes, range from 2 to 20 million; we carry around mostly microbial genes! –Dr. Rob Knight, “How microbes could cure disease: Rob Knight at TED2014”
“It is precisely due to our microbiome, and the micobiota that it contains, that we are able to even live as they give us all the genes and proteins our human genome does not encode.”
“You can think of it as: humans are actually the bystanders; it is the microbiota that does all of the work.”
In general, humans have very similar DNA, but our microbiome’s differ tremendously. Additionally, each of our externally exposed microbiome regions differs from one another which makes sense since the microbiome preforms different functions for different parts of our body. What was more amazing, was that our individual microbiome regions are virtually changing. Only in 2012 did we learn that the vaginal microbiome alters throughout pregnancy ultimately becoming much less diverse and increasing tremendously in certain specific bacterial species: This study1, showed Proteobacteria (usually associated with inflammation) and Actinobacteria species (more common in metabolic syndrome2 ) increased, and this study showed Lactobacillus species (prevents the growth of harmful bacteria and aids human digestion) increased, despite the newborn microbiota (inoculation during vaginal delivery) resembling the mother’s first trimester vaginal microbiome. If interested, see reference 6 below for further discussion. Additionally, you can read this post, “Microbiome, What Disrupts It?” and this post, “Microbiome Rules, What Is It?” to better understand some of the factors that determines, disrupts, and alters the microbiome communities.
THE ROLE OF THE MICROBIOME
Many vital host functions are provided by the microbiota including the synthesis of vitamins and antibiotics that we can not currently commercially manufacture, digestion of complex polysaccharides, maintenance of the intestinal epithelial barrier, and resistance to pathogen colonization. “It is precisely due to our microbiome, and the micobiota that it contains, that we are able to even live as they give us all the genes and proteins our human genome does not encode. You can think of it as: humans are actually the bystanders; it is the microbiota that does all of the work.” ~‘Animated Life: Seeing the Invisible’
Millions of years of co-evolution have inextricably linked the health of mammals to their microbiota. We have a lot of catch up using gene sequencing technology since not a lot of what was seen under the microscope was ever culture-able. Estimates range from only 0.1% to 1% of that seen microscopically is culture-able, or that 99% is not culture-able! And that which is culture-able may not even be the most abundant nor may it be very important. This is now called “The Great Plate Anomaly.” An example of a major game changer: for decades we easily grew e-coli in a culture dish with medium thinking, since it grew so well, it was a predominant player in our gut. Well, truth now be told, e-coli is only one cell in a million in a healthy gut. Realize this significance: your doctor’s throat culture can’t detect 99% of the bacteria present for diagnosis perhaps giving new meaning to the term “broad spectrum antibiotic.”
Another game changer for microbiome research involves keeping the DNA alive. DNA sequencing now looks at dead DNA. The microbiome is anaerobic thus, new devices (see below slides), techniques and growing mediums that remove oxygen and keep the DNA alive are being used to gather data. Future application of this technology will allow input of probiotics, or soil fertilizers… and researchers will be able to see in real time, microbiome effects. Another brillant researcher evaluating the fermenting real time gut microbiome would be Dr. Emma Allen-Vercoe who presented at the 1st International Symposium on the Microbiome in Health and Disease with a Special Focus on Autism. Realize… microbiome research has only just begun and truly mimics the mission, “to explore strange new worlds, to seek out new life and new civilizations, to boldly go where no man has gone before,” should you be a Star Trek fan.
Specific gut bacteria direct the development of the mammalian immune system and confer protection from intestinal diseases; thus fundamental aspects of health are absolutely dependent on microbial symbiosis.
Western societies, recent epidemiologic and clinical reports have revealed dramatic increases in the incidences of inflammatory (chronic disease) and immune disorders including inflammatory bowel disease, asthma, type 1 diabetes, and multiple sclerosis (see below slide).
The “American Gut” project and others, have documented how different the Western microbiome (blue on below slide) is from the rest of non-Western microbiomes.
The hygiene hypothesis proposed two decades ago speculated that these increases are the result of lifestyle changes and medical advances that reduce exposure to microbial pathogens AND that knock out our microbiota.
Astonishingly, the disorders involve a common immunologic defect found in the absence of intestinal bacteria. The question then becomes: After eons of co-evolution with our microbial partners, have societal advances (including sanitation, ‘western’ diets, and antibiotics) paradoxically affected human health adversely by reducing our exposure to health-promoting bacteria both from the environment and from our microbiota? Studies now say, “Yes!”
WE ARE SICKER WHEN WE HAVE LESS BACTERIA ONBOARD WITHIN OUR MICROBIOME
Humans depend on crucial by-products of the microbiome which includes the collective genomes of our intestinal bacterial species, which outnumber our human genome by 10:1. The microbiome harnesses nutrients through fermentation of complex sugars passing through the intestine and generates a large array of metabolites. This study from “Nutrition and Diabetes,“ is a goldmine for short chain fatty acid (SCFA) discussion, but for now, understand that it is a very important metabolite as it affects immunity, strengthens the intestinal wall, and feeds the cells lining the gut (see below slide). Many Americans are deficient of SCFA due to the low fiber consumption inherent in the Standard American Diet – but the story does not end there. See further discussion of SCFA in my notes section at the end of this post as those overweight and obese actually had increased SCFA which is contradictory of the current thinking, that increased fiber reduces the risk of obesity. Thus, it seems to be the microbiome community that dictates the metabolism of SCFA and thus resultant health ramifications, and an excess of SCFA may not be healthy see the post link Prebiotics, Gut Health, and Weight Loss (Dr. Ruscio).
When the microbiome community diversity and/or those species critical for providing beneficial by-products are reduced, we lack the optimal life sustaining necessities for immunity and thus negatively impact health, wellness, and vitality.
Additionally, pathogenic microbiota can slip into the ecosystem void and flourish furthering the risk of disease.
Advances using genomic, microbiologic, immunologic methods and animal models in the last few years now make it possible to mine this untapped reservoir for beneficial microbial molecules. Many labs (see references below) have the goals of defining the molecular processes evolved by symbiotic bacteria that mediate protection from inflammatory (chronic disease) and autoimmune diseases.
Intriguing connections between gut bacteria and behavioral and neurodegenerative disorders, autoimmunity, and inflammatory chronic disease have been found (see the drop down menu on the top right sidebar titled “The Science Behind Food And Disease” for specific disease/microbiome correlations which is also pictured on the below slide, but note: correlation does not mean causation). Labs are now investigating how the microbiome regulates the gut-immune-chronic disease, autoimmune, as well as brain axis which may lead to novel therapies for enigmatic diseases based upon an understanding of the beneficial immune, organ/tissue or neurological responses promoted by symbiotic gut bacteria which may lead to the development of natural therapeutics based on entirely novel biological principles.
Dr. Rob Knight’s October 18, 2014 lecture detailed current microbiome research and provided an eleven point list of what has been shown thus far, to be most beneficial for the microbiome cautioning all is preliminary.
You can harness the information to optimize your microbiome recognizing that everyone is different. The right diet depends a lot on the individual and that individual’s microbes.
WHAT ARE THE MICROBIOME EXPERTS SAYING ABOUT TRANSLATING HUMAN MICROBIOME RESEARCH INTO CLINICAL PRACTICE?
This study was 60 in-depth, semi-structured interviews (2009-2010) with 63 researchers and National Institutes of Health project leaders (‘investigators’) involved with human microbiome research. The interviews explored a range of ethical, legal and social implications of human microbiome research, including investigators’ perspectives on potential strategies for translating findings to clinical practice. The conclusions:
• We need to consider embracing a new paradigm of health and
disease, further delineate the importance of microbial communities and pursue the potential clinical utility of this research,
• We should consider avoiding the use of rhetorical devices used to construct bacteria as invaders, not co-habitants, of the human body (i.e. ‘germ warfare,’‘sterilizing our exterior,’ etc), and
• [This research] will yield ‘multiple applications that will be quite relevant to science and medicine’ (investigator 101), ‘fundamentally shift[ing] medicine and medical treatment’ (investigator 140) and [will] revolutionize medicine, clinical
practice and ‘how we treat human health’ (investigator 162).
Dr. Rob Knight”s eleven point punch list of things that seem to be beneficial to the microbiome:
- Eat lots of plants: 5 to 30 different varieties each week preferably. See MY NOTES below for more explanation.
- Aging increases microbiome diversity: Microbiomes are more diverse at age 50 to 60 then populations in their twenties (see below slides).
- Having an IBD diagnosis means your microbiome is altered. NOTE: Many chronic and autoimmune diseases are also following suit.
- The time of year alters the microbiome with a more diverse microbiome being with sun and outdoor exposure.
- Antibiotics wipe the microbiome with some folks recovering relatively soon whereas others do not recover the pre-antibiotic microbiome even one year later.
- Males vs females: The sex for a given microbiome can now be accurately predicted.
- Sleep 8 hours for a more diverse microbiome. Less than 6 hours yields a less diverse microbiome.
- BMI but it only subtly affects the microbiome.
- Plants: eating 6 to 10 each week is good, but eating 30 plus different varieties is best. (See further discussion below.)
- Alcohol: one drink is helpful, more than one reduces diversity.
- Frequent exercisers have a more diverse microbiome and it is best if exercise is outdoors rather than indoors.
Eat lots of plants: 5 to 30 different varieties each week preferably – MY NOTES:
This finding is so profound that “American Gut” will soon change participant food journal requirements to only ask for frequency on consumption of holistic food within the past month, instead of the three week food journal. This change is warranted since the long term diet, especially meat and fiber consumption, has been shown to have the largest effect on the microbiome.
The benefits of eating many diverse plants is as expected from general guidelines to date and it includes lots of leafy greens and brightly colored vegetables which also contains carotenoids, anthocyanins, lycopenoids, and other beneficial plant compounds.
Plants also provide fiber which the microbiome ferments; one beneficial by-product is short chain fatty acids (SCFA).
This study, from Nutrition & Diabetes, summarizes SCFA nicely: “Colonic fermentation is a complex process that occurs through the interactions of many microbial species and involves the anaerobic breakdown of dietary fibre, protein and peptides.1, 2, 3 The principal end products of colonic fermentation are the SCFA, acetate, propionate and butyrate, the gases hydrogen, carbon dioxide and methane4, 5, 6 and energy, which is used by the microbiota for growth and maintenance of cellular functions.7 Small amounts of branched chain fatty acids (iso-butyrate, valerate and iso-valerate) are also formed from protein and amino acid degradation. The amount and type of dietary fibre are among the major determinants of gut microbial composition and SCFA production patterns.8 In humans, the SCFA produced account for 5–10% of total dietary energy.9 )
However, we have a lot yet to learn regarding SCFA. This June 2014 paper notes that for overweight and obese participants, SCFA was increased. This is contradictory of the current thinking that increased fiber results in decreased risk of obesity.
This study, excerpted from Nutrition & Diabetes: “Dietary intake is a key factor in the pathophysiology of obesity, and habitual dietary intakes also have a role in determining gut microbiota composition.38, 39,40, 41, 42 No significant differences in dietary intakes between the two groups in this study were observed. Interestingly, TDF intakes were similar in the two groups even though the OWOB group had significantly higher faecal SCFA concentrations and this may imply that colonic fermentation in the obese microbiome is more efficient. It is also possible that there might have been some under reporting of dietary intakes in the OWOB group. Faecal SCFA were inversely related to the intake of TDF per 1000 kcals in LN but not in OWOB participants, which may suggest that the lean microbiome may ferment dietary fibre differently from the obese microbiome. The inverse association may also suggest that LN participants may absorb more SCFA or that there might be bacteria associated with the lean microbiome that may breakdown SCFA in order to utilize it as an energy source.
Negative correlations were also observed between PUFA intakes and various microbial phyla. Most of the genes present in the gut microbiome do not generally engage in fatty acid breakdown.43 However, studies have shown that PUFA significantly alters colonic fermentation.44, 45 In vitro studies have shown a modulatory effect of PUFA concentrations on the growth and adhesion of different Lactobacillus strains.46 In rats, a decrease in the number of Bacteroides fragilis species and total anaerobes in the caecum was observed after fish oil consumption, which is rich in long chain n-3 PUFA.47Dietary fatty acids may alter the fatty acid composition of the intestinal wall and modify the attachment site to promote or inhibit microbial colonization.
Lastly, microbiome diversity is increased by eating more variety of plants.
It is thought that greater diversity means improved immunity since many diseases (including obesity, diabetes, colon cancer and IBD…) are associated with reduced microbiome diversity. The ratio of plant to animal foods (a.k.a. the ratio of carbohydrates to protein) significantly affects the microbiome and is complex. Researchers are only now beginning to study individual foods and are learning that they vary in metabolites based on where they are grown, how they are stored, and even how they are cooked.
And there are studies showing adverse healthy consequences associated with meat consumption such as this study, which found that gut microbes metabolize L-carnitine found in red meat into TMAO, and that can lead to hardening of the arteries.
That said, there are certain diseases that modified plant/meat ratios seem to benefit such as IBS (where FODMAPS help), or gluten and casein free (or GAPS) for autism, SCD for IBD, Wahl’s diet for MS, a temporary ketogenic type diet for Type 2 Diabetes or Metabolic Syndrome, a ketogenic diet for epileptic seizures…).
References: There are many labs involved in collaboration with the microbiota research discussed on this page. Some of my favorites are:
- Sarkis Mazmanian Lab (Caltech): autism – Humans co-evolved with bacteria. There are three parts of the human that continue to evolve through-out one’s lifetime: the brain, the immune system and the microbiota. We study how these three constantly evolving parts interact and influence health and disease.
- The Knight Lab (University of Colorado Boulder) This page links to their research publications.
- The Jeff Gordon Lab (Wash U) on obesity and malnutrition.
- Jonathan Eisen’s Lab (UC Davis) on brain analolgy.
- Maria Gloria Dominguez-Bello Lab (NYU) all about babies.
- The Ruth Ley Lab (Cornell) all about babies and the vaginal microbiome, obesity and malnutrition. This article is a great launch point: “Meanwhile, after birth, the children’s microbiotas resembled those of the mothers’ first trimester samples [despite the changes that occurred in the third trimester]. Ley speculates that physiological changes that occur during pregnancy alter the microbial community, which, in turn, creates a positive-feedback loop sustaining conditions seen in metabolic syndrome. “The body might be using the microbes as a tool,” she says. “You alter the microbiota, and they give you the changes in metabolism that you want.” “That is pretty suggestive that the microbiome is at least contributing to the change, or maybe driving it,” says David Relman, a microbiologist at Stanford University in California who is looking for associations between pregnancy microbiomes and pre-term birth.”
- Dr. Emma Allen-Vercoe who presented at the “1st International Symposium on the Microbiome in Health and Disease with a Special Focus on Autism” on live fermentation of the gut microbiome.
- The Human Microbiome Project
- “The Human Microbiome: A True Story about You and Trillions of Your Closest (Microscopic) Friends,” Lita M. Proctor
Last updated: November 3, 2017 at 16:09 pm to add SCFA excess may not be good as discusssed in obesity post link Prebiotics, Gut Health, and Weight Loss (Dr. Ruscio). Prior update June 11, 2017 was for SEO Optimization.
As always, best of health through awareness,