The microbiome, our weight loss and healthy aging ally
The human body is composed of roughly 37 billion human cells and 48 trillion among bacteria, fungi and other microorganisms, collectively referred to as the microbiota or microbiome. Because of the microscopic size of these organisms, the microbiome collectively weighs in at a mere 1 to 3 percent of the human body mass, yet it astonishingly influences every single function in the body, While we host this population of bacteria across all outer and inner tissues of our body, the highest concentration dwells in our gut, mostly our large intestine, and it is therefore referred to as our gut flora. Our microbiome regulates food intake, balances blood glucose, recycles bile acids, normalizes bowel motility and boosts vitamin and mineral absorption throughout the GI tract. It is also dynamically involved in immune response, emotional health, hormone production and detoxification, inflammation and reproductive behaviors.
The power of the microbiome on how we manipulate genetics in terms of weight, body composition and aging should not be underestimated: while our human genome is composed of about 22.000 protein-coding genes, our microbiome exerts a massive epigenetic influence on our gene expression by contributing 360 times more encoding genes to our DNA sequence. We are in fact learning how our metabolic phenotype (the product of genetic and epigenetic contributions) reflects myriad functions encoded in our microbial genes. Some of these genes create essential metabolites such as B vitamins, carotenoids, vitamin K, enzymes, beneficial Omega-6 fats like CLA, and vitamin D. Studies on mice and humans have revealed that obese and overweight subjects present with more carbohydrate metabolism genes in their microbiome than non-obese subjects, while they also have scarcity of metabolically beneficial microbiome.
A well-balanced microbiome is composed of 85% beneficial bacteria and 15% pathogens, which, to the benefit of our well-being, co-exist peacefully, till they don’t: any alteration in their ratio, called dysbiosis, that gives power to the ‘bad guys’, is a precipitating factor in countless health issues. Dysbiosis, also called dysbacteriosis or microbiome dysregulation, typically due to poor diet (mainly a processed food based one), antibiotics, toxic overload and illness, causes our microbiome to lose its modulatory effects on inflammation pathways. In a normal inflammatory response, chemical mediators called cytokines are released at the site of harm, where they dilate blood vessels, draw pain producing chemicals (signaling to the immune system where to send help), and speed up healing. Fermentation products of beneficial microbes, called SCFAs, short chain fatty acids, call for a ceasefire, deterring pro-inflammatory cytokines from cascading and outspreading across all body systems. Over time, lack of SCFAs and an elevated production of pro-inflammatory LPS, lipopolysaccharides, toxic metabolites of dead or dying bacteria, crank up cytokine release and signaling; as a result, immune cells circulating in the blood stop responding and no longer rush to the site of injury. As I will detail ahead, the wildfire of unrestrained inflammation is associated with weight loss resistance, due to its impact on insulin regulation and glucose intolerance, not to mention all the inflammatory conditions such as arthritis and asthma, that make it challenging to lead an active life.
Low grade systemic inflammation is a central feature of weight loss resistance and diabetes. There are biological pathways to metabolic derangement that start as gut inflammation, while the opposite is also true. This vicious cycle correlates with conditions that speed up aging and ratchet down vitality.
Inflammation is associated in a chain reaction with a condition called LGS, leaky gut syndrome, or compromised intestinal permeability, a dysfunction of tissues lining the gut. The GI tract is lined with a single layer of cells held together by tight junction proteins, blood vessels, microorganisms and a protective mucus layer. In LGS, the tight protein junctions come unglued due an elevated production of a molecule called zonulin, whose function is to open the gaps between cells to allow exchange of solutes and nutrients. The intestinal barrier becomes too permeable to keep by-products of digestion, pathogens and undigested food particles, from infiltrating the bloodstream. Overproduction of zonulin may be triggered by consumption of gluten and gliadin, and by dysbiotic conditions such as fungal overgrowth (candida), SIBO (small intestinal bacteria overgrowth), and parasitic infections. Food intolerances determined by genetics, age-related food sensitivities due to a decline in enzymes, and a diet high in grains and lectin rich foods may ramp up zonulin production to excess. Metabolic research unambiguously points to the role of leaky gut in the pathogenesis of obesity, diabetes and related metabolic disorders: LPS endotoxins translocating into the bloodstream elicit a robust response by the immune system, impair insulin signaling by damaging pancreatic beta cells, and reduce glucose transport and metabolism. In a more direct mechanism of action, intestinal barrier damage can cause these toxic metabolites to flow into the liver, causing or aggravating a series of liver diseases like NAFLD, non-alcoholic fatty liver disease. Serum LPS activity and high triglyceride concentration, a consequence of fatty liver disease, have been shown to have a joint effect on visceral obesity, chronic metabolic issues, diabetes and cardiovascular disease.
A leaky gut causes protein malabsorption, which could lead to hypothyroidism and other hormonal dysfunctions associated with a subpar metabolic rate. This outcome of leaky gut is also of great relevance to the aging population: protein malabsorption accelerates age-related sarcopenia (the gradual loss of muscle mass), slows down RMR and worsens many age-related conditions, including fatigue, poor muscle tone, saggy skin and brittle hair.
A subset of our microbiome, called estrobolome, is indirectly but impactfully involved in metabolism and weight management, in that it plays a role in estrogen balance in the body. The estrobolome produces an enzyme called β-glucuronidase, needed for carbohydrate metabolism and for a detoxification pathway called glucuronidation, which expels disease-causing biological waste products and hormones. But beta-glucuronidase has a duplicitous mechanism of action: it can prevent used up estrogens from being excreted by the liver, by reconverting them to their active form so they can be reabsorbed by the body. If levels of the good estrogens run low, this may be a positive thing. However, in states of estrogen dominance, where less desirable estrogens abound, as is largely the case this day and age, excess beta-glucuronidase sabotages the detoxification of cancer-causing estrogen metabolites.
Keeping the microbiome in balance is a prerequisite for healthy weight management.
As mentioned earlier, a balanced microflora has an ideal 85/15 ratio, with the largest percentage being our beneficial bacteria. The trillions of bacteria we harbor belong to at least 1000 different species, consisting of over 3 million genes, and two thirds of the gut bacterial species are unique to each individual. Since different species have different genetic and epigenetic influences on the biosynthesis and metabolism of nutrients, diversity of bacterial species is key to keeping the microflora working for and not against us. An important discovery has been made, through numerous human studies, with respect to the role of the microbiome in weight management and metabolic health: two specific strains of commensal gut bacteria that affect body composition and weight, called Firmicutes and Bacteroidetes. An excess of firmicutes and/or a drop in bacteroidetes is seen in communities of obese individuals and is commonly associated with impaired metabolic homeostasis, hence conditions like Type 2 Diabetes, NAFLD and elevated markers of inflammation. Testing for microbiome functionality is done by stool sample analysis. However, in my opinion, testing needs to be targeted for specific conditions that are being investigated, since our overall gut flora landscape ratios fluctuate quickly. It is always a good idea to refer to a nutrition specialist or healthcare practitioner for guidance.
Sound nutrition habits foster efficient bacterial diversity. Prebiotic foods like soluble fiber and other compounds (inulin, fructo-oligosaccharides, galacto-oligosaccharides) feed beneficial gut bacteria, while insoluble fiber feeds the cells of the colon and moves waste through, priming the gut for good bacteria proliferation. A study by the American Gut Project showed that people who ate 30 or more different plants each week had a more diverse microbiome than those who consumed 10 or fewer plants per week. In conjunction, eliminating processed foods and all sources of added sugar, particularly fructose, protects the good bacteria, and keeps the bad bacteria from overthrowing them. Probiotic foods teem with healthy bacteria, hence they directly increase our population of benefic micro-organisms. Postbiotic compounds are the end product of fiber digestion by probiotic bacteria. Postbiotic substances include B vitamins, K vitamins, amino acids, enzymes and antimicrobial peptides. One class of postbiotics known as short chain fatty acids, mentioned earlier in this article, is particularly beneficial to our health. Butyric acid is one of the most potent types of SCFAs in feeding good bacteria and supporting a strong immune response in the colon lining, counteracting allergies, infections, viruses and inflammation. Postbiotics help in the management of IBD (inflammatory bowel disease) conditions such as Chron’s and Ulcerative Colitis. SCFAs help control hunger signals, one of their important roles in weight management. Postbiotic production is increased by consumption of prebiotic/probiotic foods.
Prebiotic foods include: green leafy vegetables, leeks, artichokes, sunchokes, tomatoes, mushrooms, legumes, garlic, blueberries, cocoa, oats, barley, potatoes, bananas. *Resistant starch foods such as green bananas, boiled and cooled off potatoes and even cold pasta support microbial life through their digestion by-products. If you are a diabetic or suffer from pre-diabetic conditions, please note the claim that resistant starches do not spike blood sugar is still the subject of debates in research settings.
Probiotic foods include: kefir, kimchi, sauerkraut, pickles, buttermilk, miso, tempeh, cottage cheese and all *fermented foods in general. Authentic imported Parmigiano Reggiano, fresh mozzarella and freshly made ricotta from a trusted producer are good probiotic foods. Commercial yogurt contains a very limited amount of probiotics; homemade yogurt has a much higher content.
*My caveats:
It is not advisable for people with a genetic histamine intolerance, mast cell activation syndrome or transient histamine sensitivity to consume fermented foods. Consumption of histamine-rich vegetables and aged foods may also pose a problem for sensitive subjects. Postbiotics may be a better choice in cases like these. Always consult your nutrition specialist before making changes to your diet.
If you are a diabetic or suffer from pre-diabetic conditions, please note that the claim that resistant starches do not spike blood sugar is still a bone of contention in research settings, and more research is needed to either corroborate or dispel the claim.
With regards to supplementation: though a probiotic supplement may be advisable in times of metabolic stress, after a course of antibiotics or for specific and targeted support, long-term (and not targeted) supplementation may actually be counterproductive. We create the ecosystem in our gut from and for the foods we eat, and in that respect we all get the microbiome we need. Hence, while we may need an abundance of different strains, we don’t need to add strains that are useless to our individual dietary regimen. When it does become necessary, restoring a healthy microbiome may take some time and may require a multi-pronged approach that involves overhauling our lifestyle.
We now know, thanks to biomedical research, that while the composition and activities of the microbiome are influenced by obesity, they are also a direct cause of it. This is beacuse the microbiome not only contributes important metabolites and energy substrates to the human host, it also governs the absorption of nutrients in the intestine, regulating energy expenditure, storage and turnover. Some strains of probiotic supplements have been proven helpful in managing weight by their ability to normalize the Firmicutes (obesogenic) to Bacteroidetes (anti-obesogenic) ratio: Lactobacillus gasseri; Lactobacillus plantarum; Lactobacillus curvatus; Lactobacillus rhamnosus; Lactobacillus sakei; Lactobacillus paracasei. The yeast Saccharomyces boulardii has demonstrated positive effects regarding obesity, insulin resistance, type II diabetes and the firmicutes-to-bacteroidetes ratio. By contrast, Lactobacillus Reuteri and some bifidobacteria are associated with weight gain.
Postbiotic supplements are slowly making their appearance on the health and wellness scene, mostly as acetate, butyrate and propionate SCFAs, but a lot more research is needed to evaluate their effectiveness, safety and side effects. A study published on PubMed Central very recently looked at the effects of SCFAs on non-alcoholic fatty liver disease and concluded that if not properly metabolized by colon cells, excess SCFAs enter the liver and peripheral circulation through the portal vein, enable the host to obtain excess energy from food more efficiently, and synthesize and store more fat to the liver.
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Sources:
https://pubmed.ncbi.nlm.nih.gov/30366757/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593644/
https://diabetes.diabetesjournals.org/content/56/7/1761
https://pubmed.ncbi.nlm.nih.gov/21248165/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660322/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376873/
https://anesthesiology.duke.edu/?p=846744
https://pubmed.ncbi.nlm.nih.gov/33139627/