This post is an article I wrote titled The Perfect Storm that was published in the January 2020 issue of the medical journal the Townsend Letter.

The Perfect Storm: Explaining the Loss of Microbiome Diversity and the Epidemic of Chronic Degenerative Diseases

The Perfect Storm, which was originally a book, and eventually a movie, was based on a true story. However, the Perfect Storm has now become a metaphor that refers to a rare combination of events or converging forces that result in a devastating outcome.

I propose that there is a ‘perfect storm’ of conditions that is responsible for the current and growing epidemic of dysbiosis. These Conditions are is directly related to the global epidemic of chronic degenerative diseases.

For centuries, plagues and infectious diseases were the primary causes of death. However, medical records show that over the past 100 years, improved living conditions, vaccines and other medical advances have resulted in the near elimination of infectious disease epidemics in most parts of the world.

Although infectious diseases have largely been eliminated, mankind is now experiencing an epidemic of chronic degenerative diseases.[1] Mankind is now experiencing epidemics of cancer[2], cardiovascular disease[3], inflammatory bowel diseases[4], metabolic syndrome[5], obesity[6], arthritis[7], Alzheimer’s disease[8], autism[9], ADHD[10], nonalcoholic fatty liver disease (NAFLD)[11], depression, anxiety and other forms of mental illness.[12] It is unprecedented to have so many types of chronic degenerative diseases escalating to epidemic proportions all at the same time.

An Epidemic of Epidemics: In this article, I will review some critical changes that have taken place since the end of World War II, which are responsible for our current epidemic of chronic degenerative diseases. The key factor I will emphasize is how these changes all contribute to disrupting the microbiome and that the resulting dysbiosis causes intestinal permeability, which promotes the development of chronic degenerative diseases.

Nutrient Decline in Food: Over the past 50-70 years, there has been a substantial and continual decline in the nutritional content of the commercially available food supply in the US.

Donald Davis and his team of researchers from the University of Texas at Austin’s Department of Chemistry and Biochemistry published a landmark study in the Journal of the American College of Nutrition (Dec. 2004) titled: Changes in USDA food composition data for 43 garden crops, 1950 to 1999.[13] They reported finding significant declines in the amount of protein and essential vitamins and minerals over the past half century. According to Dr. Davis, the primary cause of the declining nutritional in our U.S. food supply is due to changes in agricultural practices such as the use of mono-cropping, artificial fertilizers and antibiotics, which are designed to improve traits such as the size, growth rate, pest resistance in plants rather than focusing on maintaining healthy soil and growing healthy plants with nutrition.

Industrial Farming: Before World War II, the family farm population in the U.S. exceeded 30 million people, which accounted for 23 percent of the total population.[14] In the decades after World War II, a “system” of industrial agriculture evolved which relies on chemically intensive food production that features massive single-crop farms and animal production facilities. Today, the majority of American farmland is dominated by large agribusiness farms. Many agribusiness farming practices have negative consequences for the quality of food and the health of humans, animals and the environment. “Industrial” agribusiness farms produce approximately 98% of America’s food supply.[15]

Artificial Chemical Fertilizers: Farming income is not based on micronutrient density, but rather on the size of the crops they grow. Rather than focusing on the quality of the food, farmers have become increasingly concerned with the volume of food they can produce.

Plants need at least 16 nutrients to be healthy. However, after World War II, farmers learned that the addition of only three nutrients, namely nitrogen, phosphorus and potassium could significantly increase crop yields. Within a relatively short period of time, most farmers abandoned the centuries-old tradition of fertilizing their crops with organic manure and switched to the widespread use of artificial chemical fertilizers.

Studies now show that long-term application of chemical fertilizers leads to serious acidification of the soil, nutritional imbalance, deterioration of the microbiome in the root system of plants and an increase in the level of toxic metal ions in soil.[16]

Monocropping: Another big change resulting from industrialized farming was a switch from regular annual crop rotation to mono-cropping. Monoculture farming utilizes large areas of available land to grow a single crop. This method of farming became increasingly popular with large agribusiness farming companies. Large tractors, weighing as much as 15 tons, can easily work thousands of acres. However, these large tractors cause severe compaction of the soil. Subsequent plowing breaks down the surface characteristics of the soil, which leaves the soil susceptible to wind and water erosion.

Monocropping with huge expensive equipment became increasingly popular with large agribusiness farmers because it significantly reduces costs. However, when large areas of farmland are used to grow a single crop, it leads to a loss of environmental biodiversity. Connecting the dots, we see that monocrop farming leads to loss of biodiversity, which weakens the plant’s immune system and makes the crop more susceptible to pests and diseases. Enter the era of pesticides, insecticides and herbicides.[17]

Pesticides & Herbicides: Monocrop farming damages the farmland, by reducing the amount of water and nutrients the soil can retain and accelerating the loss of topsoil.[18] Monocropping also dramatically reduces biodiversity. Plants grown in a monoculture environment have weakened immune systems and do not possess the necessary defense mechanisms to withstand the impact of pests and other predators such as fungus and blight.[19] To combat these problems, farmers began steadily increasing their use of pesticides, insecticides and herbicides. In addition to being used in agriculture, these toxic chemicals are also widely used in non-agricultural areas such as pubic parks, golf courses, and urban lawns and gardens.

Although use of these chemicals increased yields, there is growing global alarm about the damage they cause to the health of animals, humans and the environment. There is a concern that when humans are exposure to trace amounts of agricultural pesticides and herbicides, can damage our human microbiome, which increases the risk of developing numerous other chronic degenerative diseases.[20]^,[21]

Glyphosate/Roundup: In my opinion, glyphosate poses a serious health risk to mankind because its widespread use throughout the world is killing the microbiome on Earth. A recent study reported that levels of glyphosate found in humans have increased by more than 1,000% in just the last 20 years.[22] A study just published in March 2019 reported that glyphosate in rats, at levels of glyphosate determined safe by the US EPA, had negative effects on sexual development and disruption of the microbiome.[23]

100,000 Times Faster: The results of the following study are incredibly frightening. Scientists conducted a study which showed that when bacteria are simultaneously exposed to herbicides like glyphosate and antibiotics, mutants with higher levels of resistance to antibiotics can evolve. The scientists conducting this study stated, “In some cases, resistance evolved 100,000 times faster.”[24] This discovery may explain why the emergence of antibiotic resistant superbug infections have developed so rapidly. International health experts are calling this a global threat to mankind.[25]

Metaorganism (plant + soil microbes): In The Human Superorganism[26], author Rodney Dietert stresses the relatively new concept that humans are a symbiotic superorganism consisting of the individual AND the approximately 100 trillion bacteria that make up his/her microbiome. Similarly, an increasing number of scientists are utilizing the term metaorganism to express the importance of plant-microbiome interrelationships.[27]

It takes more than a bunch of chemicals in the soil (artificial chemical fertilizers) for plants to be healthy. Plant health depends on soil fertility and soil fertility depends on the health of soil microorganisms as much as the chemical makeup of the soil itself. The degradation of organic matter in soil (humus) is the source of nutrients for plants. But this process cannot happen without the action of “microbial middlemen.” Soil microorganisms (bacteria and fungi) play a critical role in the health of plants. We must stop the application of artificial fertilizers and toxic pesticides such as organophosphates and herbicides such as glyphosate on plants and to the soil on planet earth. They KILL soil bacteria. Maintaining soil fertility with healthy microbes is the key to plant health and their resistance to bugs and diseases.

The destruction of life in the soil is the primary cause of plant diseases, and it is also contributing to the epidemic of chronic degenerative diseases in humans. The poisoning of life in the soil by applying artificial fertilizers and toxic agricultural chemicals is one of the most serious risks to the health of humans and nature in the history of mankind. It is imperative for the health of humans and all of nature, that we develop methods of sustainable agriculture.

One of the best sources of information on organic gardening and sustainable agriculture is Howard Garrett, who is known as The Dirt Doctor. Information about Howard’s radio show, thousands of topics, podcasts, his FREE weekly newsletter, online courses and books are available at: https://www.dirtdoctor.com.

Antibiotics: The modern-day discovery of antibiotics (sulfa drugs in the 1940s and penicillin, erythromycin, tetracycline and others in the 1950s) ranks as one of the most important discoveries of all time. However, what was initially a life-saving miracle has now developed into a critical global health crisis. In addition to disrupting the microbiome in animals, humans and the soil (pesticides are actually antibiotics) the overuse of antibiotics is resulting in the rapid development of antibiotic-resistant superbug infections.

The Centers for Disease Control and Prevention (CDC) has reported that nearly 99,000 people die each year in the United States from antibiotic-resistant bacterial infections.[28] That is more deaths than breast and prostate cancer combined.

The over prescribing of antibiotics by physicians and dentists is one part of the problem. In 2016, over 270 million outpatient antibiotic prescriptions were prescribed in the United States.[29] A 2016 Centers for Disease Control and Prevention (CDC) report estimated that at least 30% of antibiotics prescribed in US outpatient settings are unnecessary.[30] Another study published in JAMA reported that 81% of antibiotic prescriptions prescribed by dentists are not needed.[31]

Antibiotics in Animals: Antibiotic use plays a major role in the emerging global health crisis of antibiotic resistance ‘superbug’ infections. Approximately 80% of the antibiotics sold in the United States are used in animals, primarily to promote growth and prevent infections.[32] Although the majority of antibiotic use occurs in agricultural settings, very little attention is being paid to how antibiotic use in farm animals contributes to the emerging problem of antibiotic resistance infections.

Ingestion of antibiotics is the most serious cause of microbiome disruption and dysbiosis. However, as I reported in last month’s issue of the Townsend Letter (Microbiome-Disrupting Drugs[33]), there are many other classes of drugs that disrupt the human microbiome.

Antibiotic Resistant ‘Superbug’ Infections: in 2014, England’s Prime Minister David Cameron commissioned a Review on Antimicrobial Resistance (AMR). Based on the results of the commission’s report, Cameron stated, “If we fail to act, we are looking at an almost unthinkable scenario where antibiotics no longer work, and we are cast back into the dark ages of medicine.”[34] If serious action is not taken, experts predict that by 2050, antibiotic resistant infections may overtake cancer and kill over 10 million people per year.

The FIBER GAP: An article titled The Fiber Gap and the Disappearing Gut Microbiome: Implications for Human Nutrition discusses how low fiber diets are affecting people’s microbiome and ultimately, their health. The authors of this study report that 90% of children and adults in America DO NOT consume the recommended amount of daily dietary fiber.[35]

One of the most important reasons the Standard American Diet (SAD) causes human health problems is due to its low fiber content. Highly processed foods lack fiber. Fiber is the required food for your probiotic bacteria. There is increasing evidence that a lack of dietary fiber, referred to as the Fiber Gap, is one of the most critical factors contributing to the epidemic of gut dysbiosis in humans.[36]

It takes more than probiotic supplements to create and maintain a healthy microbiome. People must learn how to feed their probiotic bacteria well. If probiotic bacteria are not supplied with a diverse, fiber-rich diet, they will not thrive and survive. Thus, millions of people probably do not get much benefit from the probiotics they take because they are not consuming a wide range of fiber-rich foods.

It is essential to realize that the quantity of fiber in the daily diet is not the only fiber issue. A diversity of different kinds of fiber-rich foods is required to promote the growth of a diverse microbiome. How many different kinds of colored, fiber-rich fruits and vegetables are you feeding your probiotic bacteria today?

For an easy way to increase the diversity of fiber-rich foods in your daily diet, I suggest you Google my 8-minute YouTube video which teaches people how to save of time making salads. Just Google: Ross Salad Buzz.

This concludes my summary of the major issues that are altering human microbiomes which results in dysbiosis, intestinal permeability and ultimately, chronic degenerative diseases. The factors I’ve discuss are changes in farming practices such as mono-cropping, the use of artificial fertilizers, pesticides, insecticides and herbicides, antibiotics used in animals and humans, other microbiome-disrupting drugs discussed in Nov. 2019 issue of the Townsend Letter, and the lack of adequate fiber in American diets. Now I will continue with an explanation of how and why disruption of the microbiome and the resulting dysbiosis are largely responsible for our epidemic of chronic degenerative diseases.

Dr. Alessio Fasano & Zonulin: Dr. Fasano discovered a molecule named zonulin, which is expressed during inflammation and regulates the permeability of the tight junctions in the intestinal tract. I would not be surprised if Dr. Fasano wins the Nobel prize for discovering zonulin because I think it is one of the most important health discoveries in our lifetime. I highly recommend reading Dr. Fasano’s book Gluten Freedom[37], which provides a good summary of his discovery of zonulin and all of its implications for health.

GI Inflammation: Dr. Fasano states that the two prominent factors that cause GI inflammation and cause zonulin to be expressed are bad bacteria and gluten.[38] One of the most important aspects of Fasano’s discovery is the fact that GI inflammation and zonulin-induced intestinal permeability allows antigenic food particles, toxic agents, microorganisms, and bacterial byproducts such as highly pro-inflammatory lipopolysaccharides (LPS) to cross the gut barrier. When any of these agents enter into systemic circulation, they can induce immune responses that causes the development of diseases.

We now know that gut dysbiosis and intestinal permeability are associated with an alarmingly wide range of systemic diseases, including autoimmune diseases such as celiac disease, type-1 diabetes, IBD, colitis, multiple sclerosis, metabolic disorders including obesity, insulin resistance, Type-2 diabetes and polycystic ovary syndrome and other conditions such as asthma, coronary artery disease and cancer.[39]

Zonulin is the only human protein discovered to date that has been shown to reversibly regulate intestinal permeability by modulating intercellular tight junctions in the intestinal tract.[40] Dr. Fasano believes that that reducing inflammation and down regulating zonulin can reestablish healthy gut tight junctions.

Dr. Fasano’s new theory suggests that when these pathological disease processes are activated, they are NOT necessarily auto-perpetuating. He believes these disease processes can be arrested and, in some cases, even reversed by reducing inflammation and healing the gut.[41]

Healing the gut requires reducing inflammation. While there are many triggers that can cause inflammation, Dr. Fasano’s research suggests that the two most important factors to address are avoiding gluten and correcting bacterial imbalances or dysbiosis.

Since much of my work is focused on how to create and maintain a healthy microbiome, that is the topic I will address in regard to healing the gut. The Townsend Letter archives contain excellent articles on gluten related issues.

Postbiotic Metabolites Accelerate Gut Healing: In my article titled Postbiotic Metabolites: The New Frontier in Microbiome Science (Townsend Letter, June 2019) I introduced the topic of postbiotic metabolites and the important roles they play in regulating both GI and systemic health.

Hallmarks of dysbiosis include harmful bacteria, inflammation, an alkaline pH, poor digestion and absorption of nutrients, poor detoxification, dysregulated gut-brain communication and compromised immune function. Various types of postbiotic metabolites help to address and improve all of these issues in the microbiome ecosystem. For example, some postbiotic metabolites are classified as antimicrobial peptides (AMPs) which directly kill pathogens. Others like short-chain fatty acids (SCFAs), organic acids, amino acids and fulvic help to establish the optimal GI pH which is slightly acidic. Butyric acid is a SCFA metabolite that accelerates the growth of healthy new epithelial cells to replace cells damaged by inflammation.

The examples above are just the proverbial tip of the iceberg. In the book The Mind-Gut Connection, author Emeran Mayer, MD states that your bacteria use the information in their millions of genes to produce hundreds of thousands of metabolites. That’s why I call this the New Frontier in Microbiome Science.

Conclusion: In all ecosystems, greater species diversity creates a more stable, healthier environment. The same holds true for the human microbiome. It is critical to understand that dietary fiber is the required food for your probiotic bacteria. Ingesting a wide range of different kinds of dietary fiber is absolutely essential for a healthy, diverse microbiome. Diverse dietary fibers support the growth of a diverse range of probiotic bacteria which will in turn produce a wide range of health-regulating postbiotic metabolites. Direct ingestion of postbiotic metabolites is the fastest way to initiate healthy improvements in people suffering from dysbiosis-related GI problems.

The Future of Postbiotic Metabolites: Some commercial probiotic products are produced utilizing a multi-year fermentation process. In these fermentation production processes, organically grown fiber-rich foods are shredded and added to large fermentation vats along with starter strains of probiotic bacteria. The bacteria spend several years fermenting the food fibers to produce postbiotic metabolites. Products produced utilizing these fermentation production processes contain probiotic bacteria, prebiotic foods and hundreds of postbiotic metabolites. Directly delivering postbiotic metabolites elicits positive changes in the microbiome ecosystem much faster than just delivering probiotic bacteria.

Free Offer: Healthcare professionals, I urge you to educate yourself and your patients about the importance of postbiotic metabolites. If you would like a copy of my article Postbiotic Metabolites: The New Frontier in Microbiome Science, email a request to me at: ross@naturalpharmacist.net

Speak Up: In 2015, the International Agency for Research on Cancer (IARC), which is the specialized cancer agency of the World Health Organization (WHO) announced that glyphosate is a probable carcinogen.[42] To see a state-by-state listing of more than 100 cities in the U.S. that have banned glyphosate, go to: https://www.dirtdoctor.com/garden/Glyphosate-Where-is-Glyphosate-Banned_vq13726.htm

If your city is not on this list, I urge you to speak up and make your voice heard. Do what you can to get your community to ban glyphosate. Contact your political representatives and urge them to ban glyphosate and support sustainable agriculture. One of the best websites for information about the health risks of both GMO foods and glyphosate is Moms Across America: https://www.momsacrossamerica.com/

Urban Farming & Victory Gardens: During World War II, many people planted small gardens and grew food to help prevent food shortages because many farmers had left their farms to fight the war. These small garden plots were called Victory Gardens.

We no longer have an agricultural food supply. We have a nutrient-deficient industrial food supply dependent on artificial fertilizers and toxic chemicals. As people become increasingly concerned about the quality of food in America, there is a reemergence of Victory Gardens. It is called the Urban Farming movement. People are growing food in backyards, rooftops, balconies and in community garden plots. If you don’t have the space or time to grow a garden, consider joining a Community Supported Agriculture group (CSA), which is a popular way for consumers to buy local, seasonal food directly from local farmers. https://www.localharvest.org/csa/.

The goal of healthy aging is to reduce and postpone age-related diseases. Centenarians are frequently used as a model for healthy aging studies because of their ability to delay, or even avoid, chronic diseases. Studies of centenarians have consistently shown that the microbiome of these long-living people is more diverse compared to the microbiome of younger groups of people.[43]^,[44]

The bottom line: do everything you can to purchase and consume nutrient dense fiber-rich food that is grown on healthy soil and….do everything you can to create and maintain a healthy microbiome.

FREE COPY: If you would like a free copy of my Quick Reference Guide to Drug-Induced Nutrient Depletions, send an email request to: ross@naturalpharmacist.net.

REFERENCES:

[1] Perk J. Non-communicable diseases, a growing threat to global health. European Society of Cardiology. 2017 Aug 30;15(14).

[2] Shih YC and Hurria A. Preparing for an epidemic: cancer care in an aging population. Am Soc Clin Oncol Edu Book. 2014:133-7.

[3] Ounpuu S, et al. The impending global epidemic of cardiovascular diseases. Eur Heart J. 2000 Jun;21(11):880-803.

[4] Malmborg P and Hildebrand H. The emerging global epidemic of paediatric inflammatory bowel disease-causes and consequences. J Intern Med. 2016 Mar;279(3):241-58.

[5] Saklayen MG. The Global Epidemic of the Metabolic Syndrome. Curr Hypertens Rep. 2018 Feb 26;20(2):12.

[6] Kim R. et al. Understanding the obesity epidemic. BMJ. 2019 Jul 3;366:14409.

[7] New M./ Arthritis: an impending public health epidemic. J Okla State Med Assoc. 2001 Feb;94(2):63-64.

[8] Lee TS and Krishnan KR. Alzheimer’s disease-the inexorable epidemic. Ann Acad Med Singapore. 2019 Jul;39(7):505-2.

[9] Graf WE. Et al. The autism “epidemic”: Ethical, legal, and social issues in a developmental spectrum disorder. Neurology. 2017 Apr 4;88(14):1371-1380.

[10] Lardizabal A. Is financial gain to blame for the growing ADHD epidemic? J Child Adolesc Psychiatr Nurs. 2012 Aug;25(3):164.

[11] NAFLD-NASH:An Under-Recognized Epidemic. Curr Vasc Pharmacol. 2018;16(3):209-213.

[12] Tucci V and Moukaddam N. We are the hollow men: The worldwide epidemic of mental illness, psychiatric and behavioral emergencies, and its impact on patients and providers. J Emerg Trauma Shock. 2017 Jan-Mar;10(1):4-6.

[13] Davis DR. Changes in USDA food composition data for 43 garden crops, 1950 to 1999. J Am Coll Nutr. 2004 Dec;23(6):669-82.

[14] R. Douglas Hurt, Problems of Plenty: The American Farmer in the Twentieth Century. (Chicago: Ivan R. Dee, 2002), 120.

[15] Windham JS. Putting Your Money Where Your Mouth Is: Perverse Food Subsidies, Social Responsibility & America's 2007 Farm Bill, 31 ENVIRONS ENVTL. L. & POL'YJ. 1, 3 (2007).

[16] Weiwei L, et al. The effects of chemical and organic fertilizer usage on rhizosphere soil in tea orchards. PLoS One. 2019;14(5):e0217018.

[17] Power AF and Flecker AS. Agroecosystems and Biodiversity. Smithsonian National Zoological Park Conservation Biology Institute. https://nationalzoo.si.edu/scbi/migratorybirds/research/cacao/power.cfm

[18] Shannon, Kerry L., et al. Food System Policy, Public Health, and Human Rights in the United States. Annual review of public health 36 (2015): 151-173.

[19] Altieri MA and Nicholls CI. Ecological Impacts of Modern Agriculture in the United States and Latin America. Globalization and the Rural Environment.

[20] Nicolopoulou-Stamati P, et al. Chemical Pesticides and Human Health: The Urgent Need for a New Concept in Agriculture. Front Public Health. 2016;4:148.

[21] European Commission Press Release 2017: Glyphosate.
Available from: http://europa.eu/rapid/press-release_IP-17-5191_en.htm

[22] Mills PJ, et al. Excretion of the Herbicide Glyphosate in Older Adults Between 1993 and 2016. JAMA. 2017318(16):1610-1611.

[23] Manservisi F, et al. The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system. Environ Health. 20

[24] Kurenbach B, et al. Agrichemicals and antibiotics in combination increase antibiotic resistance evolution. PeerJ. 2018;6:5801.

[25] Roca I. et al. The global threat of antimicrobial resistance: science for intervention. New Microbes and New Infections. July 2015;6:22-29.

[26] Dietert R. The Human Superorganism. (New York, NY: Dutton, 2016)

[27] Thijs S, et al. Towards an Enhanced Understanding of Plant–Microbiome Interactions to Improve Phytoremediation: Engineering the Metaorganism. Front Microbiol. 2016;7:341.

[28] Klevens RM, Edwards JR, Richards CL Jr., et al. Estimating Healthcare-Associated Infections and Deaths in US Hospitals. Public Health Rep. 122:160–166;2007.

[29] Outpatient antibiotic prescriptions – United States, 2016. https://www.cdc.gov/antibiotic-use/community/pdfs/Annual-Report-2016-H.pdf

[30] Fleming-Dutra K, et al. Prevalence of Inappropriate Antibiotic Prescriptions Among US Ambulatory Care Visits, 2010-2011. JAMA. May 3, 2016;315(17):1864-1873.

[31] Suda KJ, et al. Assessment of the Appropriateness of Antibiotic Prescriptions for Infection Prophylaxis Before Dental Procedures, 2011 to 2015. JAMA Network Open. 2019;2(5):e193909.

[32] Ventola CL. The Antibiotic Resistance Crisis. Part 1: Causes and Threats. Pharmacy & Therapeutics. 2015 Apr;40(4):277-283.

[33] Pelton R. Microbiome-Disrupting Drugs. Townsend Letter. Nov 2019; 437.

[34] Review on Antimicrobial Resistance: Tackling drug-resistant infections globally. https://amr-review.org/

[35] Clemens R. et al. Filling America’s Fiber Intake Gap: Summary of a Roundtable to Probe Realistic Solutions with a Focus on Grain-Based Foods. Journal of Nutrition. 2012 July; 142(7): 1390S-1401S.

[36] Deehan EC and Walter J. The Fiber Gap and the Disappearing Gut Microbiome: Implications for Human Nutrition. Science & Society. May 1, 2016;27(6):239-242.

[37] Fasano A. Gluten Freedom. New York, NE, Turner Publishing Company, 2014.

[38] Fasano A. Zonulin, regulation of tight junctions, and autoimmune diseases. Ann N Y Acad Sci. 2012 Jul;1258(1):25-33.

[39] Sturgeon C and Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016;4(4):e1251384.

[40] Fasano A, et al. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet. 2000;355:1518–1519.

[41] Fasano A. Zonulin, regulation of tight junctions, and autoimmune diseases. Ann N Y Acad Sci. 2012 Jul;1258(1):25-33.

[42] IARC Monograph on Glyphosate. https://www.iarc.fr/featured-news/media-centre-iarc-news-glyphosate/

[43] Kong F, et al. Identification of gut microbiome signatures associated with longevity provides a promising modulation target for healthy aging. Gut Microbes. 2019;10(2):210-215.

[44] Biagi E, et al. Gut Microbiota and Extreme Longevity. Curr biol. 2016.26;1480-1485.

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