Your Gut?No, Not That One, This One
Andrew W. Campbell, MD, is the Editor in Chief of Alternative Therapies in Health and Medicine.
Corresponding author: Andrew W. Campbell, MD
What we eat in general, our diet, and how we prepare food have changed significantly in the last 60 or so years. This is most notable in industrialized countries as well as in cities all over the world. Since time immemorial, we ate food when it was available and when it was in season. After a harvest of grains, vegetables, or fruits, we ate what was gathered. As an example, we did not eat strawberries in winter. Meat consumption was rare for most people and usually it was caught or trapped in the wild. All of this has very much changed and been transformed. We now consume new strains of wheat, rice, soy, and corn, which were not available before; we have genetically modified (GM) crops and, in the United States, we use and eat more GM crops than all the other countries in the world combined. We use chemicals on and in our foods, such as insecticides, pesticides, and fungicides on vegetables and fruits. Concentrated animal feeding operations (CAFOs), which include cattle, hogs, chicken, and turkey, use antibiotics, hormones, and heavy metals, such as arsenic, in feeding these animals. For example, CAFOs use ractopamine to increase the meat content in cattle: It is a ?-agonist drug that is known to augment protein synthesis. It is also banned in 160 countries, including China, Europe, and Russia. There is widespread use of other chemicals, such as food coloring, artificial flavorings, and artificial preservatives in our foods. We use artificial sweeteners liberally and not only in soft drinks, adding to the pandemic of obesity. Salt adversely affects our cardiovascular and immune systems yet we consume, on average, more than twice the amount that we should. Salt is often added into foods we eat, especially canned goods, but also into bread and other staple foods. Bisphenol A, a plasticizer, is used in food containers, such as plastic bottles for soft drinks, other liquids, and cooking oil, and is used to line the inside of canned goods. It leaches into the contents of the container. Glass containers have mostly been replaced by plastic ones and are now much more common than ever before in all areas of our supermarkets and grocery stores. There are other chemicals we use or, we should say, overuse, such as antacids, antihistamines, histamine-2 blockers, and antibiotics. This last prescription drug has been shown to be highly overprescribed in the United States. The others are available to the general public over-the-counter. All these xenobiotics were not part of what we consumed, nor were most available and used until after World War II. As for food preparation, microwaving food and using coated pots and pans for food preparation is new as well. For generations since the beginning of humankind, we were neither exposed to these nor did they form part of our diet. And there is much more that cannot fit into this editorial.
Concurrently with all these changes in our diet, there has been a disturbing increase in autoimmune diseases, mostly in the developed countries since World War II, which suggests a possible cause and effect. This increase is both in the incidence and prevalence of autoimmune disorders, including multiple sclerosis, rheumatoid arthritis, Crohn?s disease, and type 1 diabetes mellitus.1,2 There are more than 80 autoimmune disorders where the immune system targets cells, organs, or tissues of its own body. More than 50 million Americans are affected, women much more so than men: It is one of the 10 leading causes of death in female children and women of all ages. In contrast, cancer affects 13 million Americans.3 Autoimmune disorders can be triggered by infections, environmental factors, genetic predisposition, and gut dysbiosis. They can take a long time to develop and initial symptoms are vague and nonspecific. It has been become more and more apparent recently via a number of studies that the gut plays a greater role in autoimmunity than previously thought.
The surface of the gut is approximately 200 to 300 square meters, about the size of a tennis court, and this is where we come into greatest contact with the outside world. The single cell layer of interconnected epithelial cells that line the gut have secretory, digestive, and absorptive functions. These epithelial cells are reinforced by tight junctions in the paracellular spaces between them. The tight junctions act as highly regulated gates that open and close depending on the signals from bacterial components from the lumen and cytokines, and they are essential for intestinal diffusion mechanisms. The epithelial cells are covered by mucin; this forms the initial barrier between the contents of the gut, including commensal bacteria, and the epithelial cells.4 Neuropeptides can increase the permeability of tight junctions and change the function of the mucosal barrier. Secretory IgA is one of the major components of the humoral immune system and prevents bacteria from adhering to the mucosa and prevents the penetration of antigens into the internal environment.
The intestinal epithelium is exposed on an ongoing basis to massive amounts of foreign materials that can be either beneficial or harmful. The intestinal immune system balances the protective mechanisms against intestinal pathogens with the tolerance of commensal bacteria and food antigens. This is known as oral tolerance and begins at birth.
The colonization of the gut occurs during birth and plays an essential role in the formation of the gut microbiota. Premature birth, Caesarean section versus vaginal birth, breast-feeding versus commercial formula, and other factors affect the formation of the microbiota. The importance of the microbiota affecting the patient years later has been demonstrated in studies showing the predisposition of infants delivered via Caesarean section to asthma, allergies, and autoimmune diseases later in childhood.5,6
The oral cavity, including the tongue, teeth, and periodontal tissues, carries 1012 bacteria. This is less in the stomach, about 103, and approximately double that in the terminal ileum. However, the large intestine is where we have the greatest number of bacteria?1013?of which 70% cannot be cultivated in the microbiology laboratory.7 This is more than 10 times the total amount of cells in our body. It is interesting to note that the number of genes in our intestinal microbiota is 150 greater than the number of genes in the human genome.8
Studies have shown that when the gut microbiota is changed by pharmaceutical medications, smoking, gastrointestinal transit time, and mucosal blood among others, this change can lead to responses by the immune system, thereby triggering an autoimmune disorder. Using rheumatoid arthritis as an example of an autoimmune disease triggered by changes in the gut microbiota, 75% of patients suffering from new onset rheumatoid arthritis carried Prevotella copri in their microbiota. Another interesting factor was that 37.5% of patients with psoriatic arthritis also had P copri in their gut.9
The gut and the brain communicate bidirectionally via neural, immunological, and endocrine mechanisms. The enteric nervous system, the ?second brain,? controls the gastrointestinal system. It contains more neurons than the spinal cord in the myenteric and submucosal plexuses.10 Multiple sclerosis (MS) is an autoimmune disorder that has a devastating effect on young people and leads to disability. MS has been linked in studies to elevated intestinal permeability and to infections with bacteria and viruses.11
Autoimmunity takes time to develop, and clinical disease is preceded by many years by circulating autoantibodies in the peripheral blood.12 The symptoms of autoimmune diseases are often unclear and vague, and patients are usually seen by physicians once the symptoms are more prominent and debilitating. By becoming aware of the importance of the gut microbiota and the effects on the immune system, the physician can investigate the patient?s status by selecting the right combination of laboratory immune and autoimmune markers and initiate preventive therapy with the possibility of eliminating the cause of the immune and autoimmune reaction.
- Bach JF. The effect of infections on microbiome is seen more and more as playing a large role in our immune system and in autoimmunity. N Engl J Med. 2002;347(12):911-920.
- Rook GA, Brunet LR. Microbes, immunoregulation, and the gut. Gut. 2005;54(3):317-320.
- American Autoimmune Related Diseases Association. Autoimmune disease fact sheet. AARDA Web site. http://www.aarda.org/autoimmune-information/autoimmune-statistics/. Published August 29, 2013. Accessed October 16, 2013.
- Fasano A. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living life on the edge of the wall. Am J Pathol. 2008;173(5):1243-1252.
- Renz-Polster H, David MR, Buist AS, et al. Caesarean section delivery and the risk of allergic disorders in childhood. Clin Exp Allergy. 2005;35(11):1466-1472.
- Salam MT, Margolis HG, McConnell R, McGregor JA, Avol EL, Gilliland FD. Mode of delivery is associated with asthma and allergy occurrences in children. Ann Epidemiol. 2006;16(5):341-346.
- Gill SR, Pop M, Deboy RT, et al. Metagenomic analysis of the human distal gut microbiome. Science. 2006:312(5778):1355-1359.
- Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59-65.
- Hill DA, Hoffmann C, Abt MC, et al. Metagenomic analyses reveal antibiotic-induced temporal and spatial changes in intestinal microbiota with associated alterations in immune cell homeostasis. Mucosal Immunol. 2010;3(2):148-158.
- Bienenstock J, Collins S. 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: psycho-neuroimmunology and the intestinal microbiota: clinical observations and basic mechanisms. Clin Exp Immunol. 2010;160(1):85-91.
- Yacyshyn B, Meddings J, Sadowski D, Bowen-Yacyshyn MB. Multiple sclerosis patients have peripheral blood CD45RO+ B cells and increased intestinal permeability. Dig Dis Sci. 1996;41(12):2493-2498.
- Vojdani A. Antibodies as predictors of complex autoimmune diseases and cancer. Int J Immunophatol Pharmacol. 2008:21(3):553-566.