COULD THE GUT MICROBIOTA BE THE MISSING LINK TO AUTOIMMUNITY?
Autoimmune diseases are drastically on the rise, impacting women more than men, and scientists argue the drastic increase is too significant to be attributed to genetic predisposition alone . If you or someone you know has ever been diagnosed with an autoimmune condition, you may have received this standard explanation: for whatever reason your body is attacking itself and we aren’t really sure why. This is not the whole truth of it. Yes, in simple terms your body is attacking itself and yes, we cannot be positive of the exact cause as autoimmune diseases develop as a result of genetics and environmental triggers. However, we do have significant evidence to show a strong correlation between the gut microbiota and autoimmune conditions. Before we proceed, there are a few definitions to break down so you can better understand the context of this discussion.
Antigens. Foreign particles or cells that have entered the body that appear physically different than your cells. This can be viruses, pathogens, allergens, bacteria or toxins .
Antibodies. Created by your body in response to exposure to antigens to bind specifically to the antigen and destroy or eliminate. An immune system memory in the incidence of re-exposure .
T Cells. An important cell of the adaptive immune system. Recognize and respond immediately to foreign antigens entering the body. First line response. Multiple types: helper, effector, regulatory .
B Cells. Regulated by T cells after exposure to antigens. Create antibodies. A long-term memory of the immune system so if the body is re-exposed to an antigen it is ready to attack .
Gut Microbiota/Microflora. Term used to describe the bacteria present in your gut, ‘good’ or ‘bad’ which makes up your intestinal environment.
When autoimmune conditions are present, it is important to clarify the issue does not lie in the area being attacked but rather the issue has developed in the immune system, the part of your body mounting the response. For example, Hashimoto’s Hypothyroidism is not a problem of the thyroid gland, Multiple Sclerosis (MS) is not a problem of the central nervous system, Systemic Lupus Erythematosus (SLE) is not a problem of the bone marrow; they are all a problem of a dysfunctioning, uncoordinated immune system having difficulty differentiating between foreign and self [1,4]. T Cells, which are present to recognize and attack foreign antigens, have been a primary determinant in autoimmune conditions due to the imbalance in the types and functioning [1,4,5]. The confusion between self and foreign stimulates them to create antibodies against self and also causes them to be ineffective at attacking and preventing foreign invaders from entering your system. These T Cells are only the first line of defense, by further regulating B Cells they create a memory of this immune response to repeatedly attack when re-exposed to the antigen (which, as autoimmune is part of your body, will be virtually all the time) [2,6]. While these cells circulate throughout the entire body when needed, can you guess where the majority of T Cells reside and initially encounter antigens?
Everything you consume has to pass through your gut therefore it is exposed to thousands of outside pathogens, allergens, bacteria, or foreign particles every day. It should not come as a surprise then that 70-80% of the cells that make up your immune system, including your T Cells, reside in the lining of your gut . T Cells line the inner wall of the mucosal lining of your intestine to prevent invasion and spreading of foreign objects from escaping through your intestinal lining into your system and, consequently, work in close relation to the bacteria present in your gut [3,7]. The bacteria present in your gut strongly influence how the T Cells function and consequently how your immune system responds. But these bacteria are not always the best co-workers. Dysbiosis of the gut microbiota, or alterations in ‘good’ and ‘bad’ bacteria, has been identified in almost every autoimmune condition: Hashimoto’s Hypothyroidism, MS, SLE, IBD, Type I Diabetes, Psoriasis, and so on [3,4,5,8,9]. There are multiple theories on how your gut bacteria can impact the function of T Cells but one thoroughly researched theory is that bacteria can actually mimic antigens. Bacteria can communicate and influence various, and specific, areas of the body. When bacteria ‘mimics’ antigens, it stimulates your T Cells to bind to them and develop antibodies . This creates confusion and imbalance for the immune system as it develops antibodies against its host, known as autoantibodies. Essentially, the ‘bad’ bacteria present in your gut has the ability to trick your immune system and cause dysregulation, confusion and destruction of vital cells in your organs.
Dysbiosis of the gut microbiome can also lead to the commonly discussed ‘leaky gut’ syndrome [3,5,9]. In short, this means the intestinal wall has become weakened and allows more foreign objects to pass through into the system (pathogens, viruses, and toxins) that your body views as foreign invaders. This mounts an immune response creating chronic inflammation throughout the body requiring multiple immune cells (T and B cells) to respond. We will avoid the in depth discussion on the cellular reactions that proceed this inflammatory response but as a result further disruption to T Cell balance and regulation develops increasing susceptibility to autoimmunity [3,5,9].
Without question, the gut microbiome is a strong determinant in the presence and development of autoimmunity but how does the gut microbiome become so disturbed?
This, of course, is a loaded question as the gut microbiome has been developing since before you were even born; however your environment continues to shape and develop the microbiome throughout your lifespan. The gut microbiome can be disturbed by infections and viruses (frequently, autoimmune conditions begin or flare after exposure to viruses such as Epstein Barr Virus/Mononucleosis), extended antibiotic usage, frequent NSAID usage, oral contraceptives, stress, smoking, dietary choices and gastrointestinal diseases such as SIBO .
SIBO (Small Intestinal Bacterial Overgrowth) is prominently discussed in the functional medicine world and has been crossing over to gain more widespread attention in Western medicine as well. Please note you can have dysbiosis of your gut microbiome and not have SIBO but the presence of SIBO has been found to have a strong connection to the trigger of autoimmune conditions.
SIBO occurs when there is more bacteria present in your small intestine than there should be influencing the immune system, the absorption of nutrients, digestion and creating undesirable bowel symptoms such as flatulence, bloating and diarrhea [9,10,11]. The small intestine is the first portion of your gastrointestinal tract connecting your stomach to your large intestine. In this portion of the tract, the main breakdown of food and absorption of vitamins and nutrients occurs . As compared to further down your GI tract, the beginning portion has relatively few bacteria present and as you travel further along the number of bacteria increases in your large intestine where stool is formed and excreted. In SIBO, abnormal growth of bacteria extends from what may normally be found in your large intestine into your small intestine [9,10,11]. When this occurs, dysbiosis of the small intestine is present as there is an increased number and abnormal types of bacteria present which, as mentioned previously, interferes with the response of your immune system via your T Cells [9,11]. While SIBO has been found to be initiated by viruses or pathogens such as food poisonings, it also has been found to develop due to abnormal functioning of your digestive system: slow motility, low stomach acid and abnormal anatomy .
Roughly two to three hours after you eat your digestive system has a ‘housekeeping’ service that maneuvers through your digestive tract cleaning out any leftover particles and bacteria. This is known as your Migrating Motor Complex (MMC), often that embarrassing grumble you hear between meals when you know you aren’t actually hungry . When the motility and emptying of your digestive tract is slowed, it interferes with the cleaning process as the food you previously ate takes longer to pass through before your next meal leaving no real ‘rest’ time for your MMC to kick in. Interference with this complex results in leftover, unwanted particles, pathogens, and viruses which contribute to the overgrowth of unwanted bacteria [8,9]. Additionally, sitting food from slow motility can create a feeding frenzy for the bacteria already present and waiting leading to further overgrowth and expansion of these ‘bad’ bacterias . The anatomy of the digestive tract is mostly due to genetics but can also be influenced by ulcers, diverticulitis or other structural interferences which contributes to the difficulty of food being absorbed, excreted and essentially further slowed .
One of the most commonly prescribed medications in the primary care setting are Proton Pump Inhibitors (PPIs) or antacids for the reduction of symptoms related to reflux . The function of this medication is to suppress the production of stomach acid so as to not experience associated symptoms with reflux such as heartburn and nausea (it does not heal whatever is causing the reflux in the first place, it is only symptom management). However, stomach acid is crucial to the digestive process and contributes to breaking down and processing key nutrients. Chronic usage of PPIs have been shown to alter the intestinal microflora and increase susceptibility to developing SIBO [10,11]. Some studies have shown this to occur in as little as 8 weeks while others have proven 1 year of usage of PPIs corresponds with a 50% chance of developing SIBO . PPIs are not the only medication to lead to SIBO, it is only the most evidence-based; birth control, steroids, narcotics and other medications can also contribute to slowed motility and the flourishing of unwanted bacteria in the intestines .
Nevertheless the development of SIBO, which alters the gut microbiota, is strongly associated with ‘leaky gut’, inflammation and autoimmune conditions. In fact, over half of individuals with hypothyroidism have been shown to also potentially have SIBO . Consideration could also be given to the fact that hypothyroidism slows down the motility of the GI tract and could potentiate this growth of unwanted bacteria which in turn could come full circle to interfere with the T Cells present resulting in an autoimmune condition like Hashimoto’s Hypothyroidism .
Autoimmunity is a long battle of flare-ups and periods of remission as your body is constantly attempting to rebalance the dysregulated T Cells. Often, environmental triggers are difficult to identify because the initiation phase of an autoimmune condition could be boiling for years before symptoms actually develop so it would be difficult to place blame on one circumstance that may have caused your gut dysbiosis and autoimmune condition. Most importantly, it’s imperative to leave room for grace rather than placing blame on yourself for the development of your autoimmune condition as the progression of autoimmunity goes much deeper. Even still, recognizing there are ways to alleviate symptoms, reach remission and reduce medication usage by first and foremost addressing your gut health.
Theofilopoulos AN, Kono DH, Baccala R. The multiple pathways to autoimmunity. Nat Immunol. 2017;18(7):716-724. https://go.openathens.net/redirector/liberty.edu?url=https://www.proquest.com/scholarly-journals/multiple-pathways-autoimmunity/docview/1917964860/se-2. doi: https://doi.org/10.1038/ni.3731.
Sprouse ML, Bates NA, Felix KM, Wu HJ. Impact of gut microbiota on gut-distal autoimmunity: a focus on T cells. Immunology. 2019 Apr;156(4):305-318. doi: 10.1111/imm.13037. Epub 2019 Jan 21. PMID: 30560993; PMCID: PMC6418419.
Rosenblum MD, Remedios KA, Abbas AK. Mechanisms of human autoimmunity. J Clin Invest. 2015 Jun;125(6):2228-33. doi: 10.1172/JCI78088. Epub 2015 Jun 1. PMID: 25893595; PMCID: PMC4518692.
Paray BA, Albeshr MF, Jan AT, Rather IA. Leaky Gut and Autoimmunity: An Intricate Balance in Individuals Health and the Diseased State. Int J Mol Sci. 2020 Dec 21;21(24):9770. doi: 10.3390/ijms21249770. PMID: 33371435; PMCID: PMC7767453.
Wiertsema SP, van Bergenhenegouwen J, Garssen J, Knippels LMJ. The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies. Nutrients. 2021; 13(3):886. https://doi.org/10.3390/nu13030886
van Wijk F, Cheroutre H. Mucosal T cells in gut homeostasis and inflammation. Expert Rev Clin Immunol. 2010 Jul;6(4):559-66. doi: 10.1586/eci.10.34. PMID: 20594129; PMCID: PMC2976609.
Quigley, E.M.M. The Spectrum of Small Intestinal Bacterial Overgrowth (SIBO). Curr Gastroenterol Rep 21, 3 (2019). https://doi-org.ezproxy.liberty.edu/10.1007/s11894-019-0671-z
Patil AD. Link between hypothyroidism and small intestinal bacterial overgrowth. Indian J Endocrinol Metab. 2014 May;18(3):307-9. doi: 10.4103/2230-8210.131155. PMID: 24944923; PMCID: PMC4056127.
Compare D, Pica L, Rocco A, et al. Effects of long-term PPI treatment on producing bowel symptoms and SIBO. European journal of clinical investigation. 2011;41(4):380-386. doi:10.1111/j.1365-2362.2010.02419.x
Sachdev AH, Pimentel M. Gastrointestinal bacterial overgrowth: pathogenesis and clinical significance. Ther Adv Chronic Dis. 2013 Sep;4(5):223-31. doi: 10.1177/2040622313496126. PMID: 23997926; PMCID: PMC3752184.
Collins JT, Nguyen A, Badireddy M. Anatomy, Abdomen and Pelvis, Small Intestine. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459366/