WHAT IS YOUR METABOLOME AND WHY IS IT IMPORTANT?
Whether talking about a blood, fluid, or tissue sample, the term Metabolome is the name given to the collective group of small-molecule chemicals and compounds found in said sample. These can be both endogenous (produced by the body --- vitamins, sugars, aminos, fatty acids, etc, etc) and exogenous (produced outside the body --- foods, drugs, chemical toxins, etc, etc). Four years ago the journal Nucleic Acid Research (The Human Metabolome Database in 2013) stated that, "the number of annotated metabolite entries has grown to more than 40,000." Although this number is undoubtedly far bigger now, why is any of this important as far as you and your family's health is concerned?
Metabolomics --- the study of individual or collective Metabolomes --- is a big deal because it can provide an extremely accurate and detailed picture of cellular metabolism. Avens Publishing Group (an Open Access publisher of peer reviewed journals) put it this way in a blog post called Metabolomics: Importance and Application.
"The purposes of metabolomics are timely detection of disease, such as necrosis, alzheimer’s, and inflammation, evaluation of toxicity (especially liver toxicity) in new drugs, diet strategies, and drug testing, elucidating biochemical pathways. The importance of metabolomics are that over 95% of all diagnostic clinical assays test for small molecules, 89% of all known drugs are small molecules, and 30% of identified genetic disorders occupy diseases of small molecule metabolism. Small molecules serve as co-factors and signaling molecules to thousands of proteins."
While there is certainly excitement over the the field of metabolomics, some of it is (or at least should be) tempered by the failure of of genetics to live up to it's hype (HERE). And in similar fashion to the way that epigenetics greatly controls genetic expression, your metabolome can be similarly controlled and directed. Let's take a look at just a few of the most recent studies on the metabolome to see why metabolomics is gaining importance as far as health is concerned. (Note that all studies are from mainstream medical journals and most have been cherry-picked due to restraints on time and space)
- This month's issue of Digestive Diseases (Nutrition and Liver Health) tackles a subject that few physicians want or have anything to do with ---- nutrition (HERE). "Poor nutrition is frequently associated with disorders of the liver, and a specific nutrition diagnosis is needed for providing best care and experiencing successful outcome." This first sentence provides us a big clue that the study is not from the US, but from Europe (Switzerland). "Nutrition is the set of integrated processes by which cells, tissues, organs and the whole body acquire the energy and nutrients to retain normal structure and perform the required functions. At the level of the whole body, this is achieved through dietary supply and the capacity of the body to transform the substrates and cofactors necessary for metabolism. All of these domains (diet, metabolic capacity, activity of the microbiome, body composition and the level of demand for energy and nutrients) are influenced by levels of physical activity and can vary according to physiological and pathological disease states. The liver plays a central role in establishing and maintaining these regulated processes. The use of stable isotopic probes and the more recent definition of the variability in the metabolome in different nutritional and pathological states indicate the great potential for clinical tools that would enable a more precise nutritional diagnosis." Again folks, this is from a medical journal. Maybe it's just wishful thinking or being stupidly idealistic, but I believe the day is coming when BIG PHARMA is going to be relegated to the sideline because it will be quick, simple, and inexpensive to intimately relate what you are putting in your mouth to your lab findings and health or lack of it.
- Just over a week ago, Current Medicinal Chemistry did a study on the effects of diet on health (The Food-Gut Human Axis: The Effects of Diet on Gut Microbiota and Metabolome). Not surprisingly they concluded that diet matters. "Gut microbiota, the largest symbiont community hosted in human organism, is emerging as a pivotal player in the relationship between dietary habits and health. Oral and, especially, intestinal microbes metabolize dietary components, affecting human health by producing harmful or beneficial metabolites, which are involved in the incidence and progression of several intestinal related and non-related diseases. Habitual diet (Western, Agrarian and Mediterranean omnivore diets, vegetarian, vegan and gluten-free diets) drives the composition of the gut microbiota and metabolome. Within the dietary components, polymers (mainly fibers, proteins, fat and polyphenols) that are not hydrolyzed by human enzymes seem to be the main leads of the metabolic pathways of gut microbiota, which in turn directly influences the human metabolome. Specific relationships between diet and microbes, microbes and metabolites, microbes and immune functions and microbes and/or their metabolites and some human diseases are being established." To bad that THIS CANYON makes the Grand Canyon look like a roadside ditch.
- The May issue of Radiation Research (Metabolomic Analysis of Mice Exposed to Gamma Radiation Reveals a Systemic Understanding of Total-Body Exposure) deals with metabolome as related to radiation exposure. Why might this be a big deal for you? For starters, CT SCANS provide massive doses of toxic radiation. "Diagnostic markers are needed for accidental or deliberate radiation exposure that could cause acute and chronic radiation toxicity. The degree of metabolic changes among different tissues showed perturbations in pathways including DNA methylation, energy, nucleic acid, amino acid, glutathione and bile acid metabolism. These results highlight metabolomics as a potential novel approach to understand functional alterations in the metabolome that could be adapted for use in the rapid assessment of radiation exposure....." To educate yourself as to why neither you nor your family wants a CT Scan, click the link.
- Less than a month ago, the journal Pediatric Diabetes (Metabolomics Reveals New Metabolic Perturbations in Children with Type 1 Diabetes) concluded, "Using an untargeted metabolomics approach we investigated the metabolome of children with type 1 diabetes (T1D) in comparison with healthy peers and explored the contribution of HbA1c and clinical features to the observed difference. T1D profoundly disrupts the metabolome of pediatric patients. The excess of cortisol and aldosterone may contribute to the development of macrovascular complications in adulthood, while the increase of tryptophan derivates may have a role in neuronal damage associated to hyperglycemia" Just remember, Type I Diabetes is an AUTOIMMUNE DISEASE, while TYPE II DIABETES is a disease of lifestyle.
- One short month ago today, the journal Environmental Research (The Impact of Ambient Air Pollution on the Human Blood Metabolome) stated, "We exposed 31 healthy volunteers to ambient air pollution for 5h. We measured exposure to particulate matter, particle number concentrations, absorbance, elemental/organic carbon, trace metals, secondary inorganic components, endotoxin content, gaseous pollutants, and particulate matter oxidative potential. We observed 89 robust associations between air pollutants and metabolic features two hours after exposure and 118 robust associations 18h after exposure. Some of the metabolic features that were associated with air pollutants were also associated with acute health effects. This study demonstrates for the first time the application of untargeted metabolite profiling to assess the impact of air pollution on the blood metabolome." No wonder air pollution is one of the many things now being tied to AUTISM. Makes me wonder when they'll start doing metabolomic research on VACCINES?
- Rachel Carson wrote her groundbreaking book, Silent Spring, in 1962, yet it took our government until 1972 to ban the pesticide DDT. The problem is, despite being banned in the United States, many of the countries we get food from still use it. Among other things, it's an endocrine disruptor and known XENOESTROGEN (artificial form of estrogen, causing ESTROGEN DOMINANCE in both males and females). Only three days ago, the Journal of Agriculture and Food Chemistry (Metabolomics Approach to Investigate Estrogen Receptor-Dependent and Independent Effects of DDT in the Uterus and Brain of Immature Mice) concluded that, "Previous studies have demonstrated the endocrine disruption of DDT. In this study, we used a 1H NMR based metabolomics approach to investigate the estrogenic effects of DDT (300 mg/kg) on the uterus and brain after 3 days of [exposure]." Without going into a lot of technical detail, suffice it to say that DDT has not gotten any safer over the years "Together with biological end points, metabolomics is a promising approach to study potential estrogenic chemicals." Banning DDT is why we see eagles virtually every time we go to the CURRENT RIVER, even though 20 years ago I had never seen one.
- Early last week the journal Steroids (Circulating Steroids Negatively Correlate with Tinnitus) linked ringing in the ears to circulation of ADRENAL HORMONES. Despite being told that it's simply caused by exposure to loud noises (which it can be), we learned that, "While not a disease entity in itself; symptoms of tinnitus accompany a number of diseases. Tinnitus prevalence increases with age, deteriorates one's quality of life, and may even result in suicidal behavior. Tinnitus develops in response to a variety of risk factors, otoxic substances, noise exposure, hearing disorders, and psychological alterations. Tinnitus is closely related to mood, depression, and psychological state. In the present study, we focused on alterations of the steroid metabolome and particularly neuroactive, neuroprotective, and immunomodulatory steroids in patients with tinnitus. Results indicated a significant and consistent negative correlation between tinnitus indices and intensity of adrenal steroidogenesis. The circulating steroid metabolome including hormones and neuroactive, neuroprotective, and immunomodulatory steroids negatively correlates with the degree of tinnitus due to hypothalamo-pituitary-adrenal axis malfunction. Our results may help explain the pathophysiology of tinnitus and improve its diagnosis. However, further studies are needed to verify our postulation." HPA-Axis is critical for everything related to health as noted by ENDOGUT. I will be attending a 16 hour seminar on HPA-Axis over the weekend.
- Three weeks ago, Kidney International (Evaluation of the Impact of Gut Microbiota on Uremic Solute Accumulation by a CE-TOFMS-Based Metabolomics Approach) revealed that, "Gut microbiota is involved in the metabolism of uremic solutes. Mice with renal failure under germ-free conditions demonstrated significant changes in plasma metabolites. Among 183 detected solutes, plasma levels of 11 solutes, including major uremic toxins, were significantly lower in germ-free mice than in SPF mice with renal failure. These 11 solutes were considered microbiota-derived uremic solutes. Metabolome profiling showed that these solutes were classified into three groups depending on their origins: completely derived from microbiota (indoxyl sulfate, p-cresyl sulfate), derived from both host and microbiota (dimethylglycine), and derived from both microbiota and dietary components (trimethylamine N-oxide). Microbiota-derived short-chain fatty acids and efficient amino acid utilization may have a renoprotective effect, and loss of these factors may exacerbate renal damage in germ-free mice with renal failure. Thus, microbiota contributes substantially to the production of harmful uremic solutes, but conversely, growth without microbiota has harmful effects on CKD progression." A lot of technical stuff here, the point being that metabolomics is being used for some very cool purposes. Oh, and it's one more example of why it's so important to take care of your GUT HEALTH and understand MICROBIOME.
The bottom line is that diseases leave distinct metablomic fingerprints. Once we figure out what this fingerprint looks like, the disease can be diagnosed. The problem is that most of this research has little to do with nutrition --- it's all about finding drugs to block specific metabolites or metabolic pathways. Case in point is a study from last month's issue of the Journal of Biological Chemistry --- the title of the study tells the story (Targeting of Microbe-Derived Metabolites to Improve Human Health: The Next Frontier for Drug Discovery). "Recent advances in metabolomic and genome mining approaches have uncovered a poorly understood metabolome that originates solely or in part from bacterial enzyme sources. Whether living on exposed surfaces or within our intestinal tract, our microbial inhabitants produce a remarkably diverse set of natural products and small molecule metabolites that can impact human health and disease. The gut microbe-derived metabolite trimethylamine N-oxide (TMAO) has been causally linked to the development of cardiovascular diseases. Recent studies reveal drugging this pathway can inhibit atherosclerosis development in mice." Sounds great on the surface but the problem with blocking metabolic pathways is that it always has side effects (the medical community refers to these as AR's or ADVERSE EVENTS).
The cool thing is that almost no matter what is wrong with you, whether you are dealing with CHRONIC ILLNESS or CHRONIC PAIN, you can start the ball rolling by taking matters into your own hands. Start by reading THIS POST. The second step is to sit down and formulate a WRITTEN PLAN. I get it; there might be other steps that need to be taken such as seeing a FUNCTIONAL MEDICINE SPECIALIST or a FUNCTIONAL NEUROLOGIST. The doubly cool thing is that most experts in the field agree that an ELIMINATION DIET followed by something along the line of PALEO, GAPS, or even KETOGENIC, is safe enough to start on your own (HERE).