Microbes: The Very Stuff of Life
Microbes were the first inhabitants of planet earth, and the sole inhabitants for the first 3 billion years, or so. They created the oxygen we breathe and the soil in which we grow our food. And evolutionary biologists generally agree that microbes are our ancestors — for humans and all other living species. Microbes are not only at the root of all that supports life on earth, they are the very stuff of life. We could not survive without them.
Our Gut Microbiota and Its Genome, the Microbiome
The Human Microbiome Project was launched in 2007 by the National Institute of Health. Advances in DNA sequencing technologies enabled the project to assess the microbial communities living on and within the human body. Research has found that our gut microbiota and its genome (microbiome) interact with food, environmental chemicals, antibiotics, and other pharmaceuticals to impact our health.
Essential for Health
Our bodies are host to a vast microbial ecosystem — living in symbiosis with us. These microbes include bacteria, fungi, viruses, and other species. Although some are pathogens, microbes are essential for health. For example, they produce some vitamins that we cannot make on our own, break down our food to extract nutrients, control our metabolism, regulate our appetite, help our immune systems recognize dangerous pathogens, produce anti-inflammatory compounds that fight off other disease-causing microbes, and they generate a number of neurotransmitters that impact our mood and are essential for a healthy brain and nervous system.
Changing the Course of Illness
The colon is more densely populated by microorganisms than any other place on earth. Genetic sequencing of the microorganisms in our poop gives us valuable insight into our health and risk of disease. The gastrointestinal tract must maintain tolerance to commensals (“good” bacteria) and dietary antigens (foreign bodies) while remaining responsive to pathogenic stimuli. If this balance is disrupted, inappropriate inflammatory processes can result, leading to a diseased state. (1) The natural homeostasis of gut microbial communities changes during many disease pathologies including metabolic syndrome, diabetes, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and celiac disease. In many cases, there is evidence implicating various dietary factors in the onset of these diseases. An imbalance in our microbial ecosystem is believed to account for some of the dramatic rise in autoimmune and inflammatory disorders in parts of the world where our symbiotic relationship with the microbiota has been the most affected.
Gut Microbiota and Your Immune System
Over the past few years, the field of immunology has been revolutionized by the growing understanding of the key role our colon’s microbiota plays in our immune system’s function and our overall health. The microbiota is necessary to induce regulatory mechanisms intended to support mucosal integrity and keep systemic immunity in balance so that while we are tolerant of harmless bacteria, we are still able to form adequate responses to pathogens.
Short Chain Fatty Acids Support the Mucosal Layer and Systemic Immunity
The clearest example of this balance involves the end products of microbiota’s fermentation of plant polysaccharides – substances called short-chain fatty acids (SCFAs). Eat more fiber and you’ll increase microbial SCFA production, which decreases the intestinal pH. This prevents the growth of potentially pathogenic bacteria such as E. coli — and SCFAs promote gut barrier integrity and reduce unnecessary immune responses and inflammation. Conversely, diminished mucosal nutrition may lead to mucosal atrophy, diminished fluid absorption, and eventually to colitis. SCFAs have also been shown to affect colonic mucosal blood flow, ileal motility, cecal mucin secretion, and mucosal cell proliferation.
Although the beneficial effects of fiber are often attributed to the increased production of SCFAs, soluble fiber can also affect other intestinal characteristics influencing intestinal health, such as increased fecal bulk, shortened colonic transit time, changes in the composition of the gut microbiota, lowered intraluminal pH, and changed bile acid profiles. Sadly, most Americans only eat about half the recommended 30 grams of fiber daily, which can negatively affect both the amount and diversity of bacterial species in the gut.
Trimethylamine N-oxide (TMAO) — A Gut-Heart Connection
Trimethylamine N-oxide (TMAO) is a common metabolite in animals. In humans, there exists a positive correlation between elevated plasma levels of TMAO and an increased risk for major adverse cardiovascular events and death. Despite the accumulating evidence that elevated TMAO levels are associated with elevated risk of heart attack and stroke, it is questioned whether TMAO itself is the mediator, or whether it is a bystander in the disease process.
Heritability of TMAO was studied in a genome-wide association study (GWAS) involving 1973 humans. It concluded that genes play only a marginal role in determining TMAO levels. However, it has been determined that a number of factors including diet, gut microbial flora, liver enzymes, and kidney function do play key roles in determining our serum TMAO levels. (15 Valesquez)
Human and animal studies suggest that several families of bacteria are involved in TMA/TMAO production. Animal studies have shown that TMAO accumulates in the serum of animals colonized with TMA-producing bacteria, but not in animals colonized with bacteria that do not generate TMA from choline in vitro. (In vitro means taking place in a test tube, culture dish, or elsewhere outside a living organism.)
A simplified model of the metabolic process is as follows: When we ingest certain nutrients, such as choline (a vitamin-like nutrient abundant in meat, egg yolks, and dairy products) and L-carnitine (a nonessential amino acid found in red meat as well as some energy drinks and supplements), the gut bacteria that break it down produce a compound called trimethylamine (TMA). The liver then converts TMA into trimethylene N-oxide (TMAO). Increased TMAO levels are associated with platelets becoming more prone to clotting. It is hypothesized that TMAO directly alters platelet function, increasing thrombosis (blood clotting) potential, and thus elevating heart attack and stroke risk.
Studies suggest that positively altering the gut microbiota may help to reduce damage to blood vessels, resulting in a stronger cardiovascular system, which points to targets for potential new heart disease therapies. Although, studies have also found that vegans and those who avoid animal products have low levels of circulating TMAO. (16 Zhu)
High-fat, Low-fiber Diets
Gut microbiota regulate genes that affect inflammation, the development of insulin resistance (prediabetes), and fat deposition. All of these abnormalities, driven by interactions between our diet and our microbiome, are triggered by high-fat low-fiber diets. (5,6) It is not surprising that, during the later half of the 20th century, escalating consumption of fat, sugar and artificial sweeteners in Western countries parallels increased incidence of Crohn’s Disease — a type of inflammatory bowel disease whereby the immune system attacks the digestive tract.
Often, it is not the presence of a pathogen that indicates disease or disease risk, but rather dysbiosis — an imbalance in our microbial ecosystem. Researchers are discovering that dysbiosis is not only associated with many disease states but is the root cause. can lead to an overgrowth of harmful bacteria and diminished numbers of commensals — the good bacteria in our gut. Rebalancing the gut ecosystem with proper nutrition is key to preserving and restoring gut health.
An overgrowth of harmful bacteria and diminished numbers of commensals — the good bacteria in our gut — has been linked to the following:
- Alcohol consumption
- Animal fat
- Acid-suppressing drugs
- Birth-control pills
- Chlorinated water
- Herbicides (on fruits and vegetables)
- Hormone therapy
- Nutrient-poor diet
- Sugar consumption
Gut dysbiosis has been associated with the following:
- Autoimmune diseases
- Cardiovascular disease
- Chronic fatigue syndrome
- Chronic inflammation and age-related diseases
- Chronic kidney disease
- Colorectal cancer
- Crohn’s disease
- Depression and anxiety
- Food allergies
- Inflammatory bowel disease
- Irritable bowel syndrome
- Multiple sclerosis
- Parkinson’s disease
- Small intestinal bacterial overgrowth (SIBO)
- Transient ischemic stroke
- Type 2 diabetes
- Ulcerative colitis
Refined sugars mediate the overgrowth of opportunistic bacteria like C. difficile (8) and C. perfringens. (9). The onset of dysbiosis is typically accompanied by bloating, and too much sugar results in overgrowth of lots of undesirable species whose waste products include bloat-forming gas. Excessive sugar consumption can also cause overgrowth of yeast species such as candida, which is associated with fatigue, leaky gut syndrome, and many other health problems.
Crosstalk Between Intestinal Epithelial Cells, Intestinal Microbes, and Immune Cells
On a cellular level, the dynamic crosstalk between intestinal epithelial cells, intestinal microbes, and local immune cells represents one of the fundamental features of normal intestinal homeostasis. These interactions are essential for mounting protective immunity to pathogens. (2) Evidence suggests that dysbiosis in the colon contributes to the pathogenesis of many diseases including metabolic syndrome, obesity, irritable bowel syndrome, inflammatory bowel disease, some cancers, type 2 diabetes, autoimmune diseases, cardiovascular disease, and even depression.
Microbiome Analysis Begins With Your Dietary Enterotype
The intestinal microbiota is composed by 17 families, 50 genera and more than 1000 species of bacteria. The intestinal microbiota is dominated by four main phyla: Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. In the adult, Bacteroidetes and Firmicutes are usually prevalent and Actinobacteria and Proteobacteria are less represented.
The composition of the gut microbiota is not associated with gender, age, or body weight but are largely influenced by long-term dietary habits. If you eat a diet high in animal protein and fat, you’ll promote an increase in microbes that thrive in a high-protein, high-fat environment (e.g. Bacteroides). In contrast, consuming a diet rich in plant foods promotes a very different gut ecology (e.g. Prevotella).
A Colorectal Cancer Enterotype
Dietary intake of red meat, poultry, dairy, and eggs are consistently associated with relative increases in certain bacteria and decreases in others. These changes have been referred to as a colorectal carcinoma enterotype. With a personal or familial history of colorectal carcinoma, an elevated genetic risk score for colon cancer, and the microbiome fingerprint of colon cancer risk, you’ll want to reduce your intake of animal products and maintain regular interval surveillance testing for colon cancer. (10)
Your Microbiome is Unique to You
Your microbiome is complex, varied, ever-changing, and unique to you. Evidence suggests that our genetics pre-programs the ecology of our GI tracts. However, there is growing evidence that the microbial ecology can be influenced by several epigenetic factors. It is a product of the genes you inherited, but also, whether you were born naturally or via c-section, whether you were breast fed or bottle fed, whether you took antibiotics and the kinds of antibiotics you took, whether you’ve lived a high-stress or low-stress life, and whether you took antacids, oral contraceptives, steroids, and so on.
Diet Plays the Dominant Role in Shaping Gut Microbiota
Research indicates that diet plays the dominant role in shaping gut microbiota. And our microbiota play a significant role in determining whether we absorb and assimilate the nutrients we consume. Food can’t be fully broken down and nutrients and vitamins can’t be properly absorbed without adequate amounts of essential gut bacteria. Changing key bacteria populations may transform healthy gut microbiota into a disease-inducing entity, and conversely, changing key populations may transform disease-inducing microbiota into a health-inducing entity. The “Western” diet, which is high in sugar and fat, causes dysbiosis which affects both host GI tract metabolism and immune homeostasis. Lifestyle and dietary interventions can reverse dysbiosis and promote a healthy microbial ecosystem.
Obesity and Artificial Sweeteners
In 2014, a team of Israeli scientists concluded from studies of mice that ingesting artificial sweeteners might lead to—of all things—obesity and related ailments such as diabetes. This was not the first animal study to note this link. Researchers have also found that people who used artificial sweeteners were more likely than others to be overweight and more likely to have impaired glucose tolerance.
Stanford University microbiologist David Relman says his findings suggests that the bacteria in the human gut may not only influence our ability to extract calories and store energy from our diet but also have an impact on the balance of hormones, such as leptin, that shape our very eating behavior, leading some of us to eat more than others in any given situation. It has also been found that the ratio of Bacteroidetes to Firmicutes bacteria increases as fat people lose weight, suggesting that an imbalance in bacteria manipulates the genes in ways that trigger the storage of fat rather than its breakdown for energy. (11)
Prescribing a Healthy Gut Protocol Relies on Multiple Factors
Your gut microbiota data, information on the tens of trillions of organisms living in your gut, will tell us whether your gut ecology is in, or out of, balance. That is, whether it contributes to your health and well being or whether it contributes to poor health.
The gut microbiome is complex, but moreover, prescribing a healthy gut protocol relies on multiple factors: a well-taken medical history, a complete physical exam, a comprehensive genetic risk evaluation, analysis of your dietary diary, and an assessment of your stress level and sleeping habits — not just an analysis of your gut microbial ecology.
Our Microbiome Analysis
Our analysis of your gut microbiome results includes an examination of the SCFA producing organisms, along with “good” bacteria associated with health and those associated with specific disease states. From this analysis, we’ll get a sense of whether or not your diet contains adequate fiber and health-promoting bacteria. Our dietary and probiotic recommendations will help you restore good gut bacteria so you can get back on track to a healthier, happier you.
A Focused Look at Micronutrients
Our analysis includes an assessment of intestinal microbiota known to synthesize vitamins, including cobalamin (vitamin B12), vitamin B6, pantothenic acid (vitamin B5), niacin (vitamin B3), biotin, tetrahydrofolate (generated from dietary forms of folate) and vitamin K. Taken together, this group of bacteria make valuable contributions to genomic stability and cardiovascular health.
Deficiencies in Vitamin A have been shown to affect the composition of the microbiota and, in turn, impair the immune response. Most notably, low levels of vitamin A are associated with higher levels of the pathobiont Bacteroides vulgatus. High levels of B. vulgatus have been linked to chronic inflammatory bowel disease and obesity. (10, 11)
At The Harlin Center, we recommend specific dietary interventions that offer a means for altering the intestinal microbial structure, changing the course of many intestinal and systemic disorders. You may be given a prescription for specific dietary and lifestyle modifications, a limited duration prescription for a specific medical food (probiotic), and, if appropriate, a prebiotic supplement.
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