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While many factors can influence thyroid health, emerging evidence indicates that there&rsffquo;s also a correlation between gut health and thyroid function. In fact, conditions related to the gut, such as celiac disease and non-celiac wheat sensitivity (NCGS), often co-occur with autoimmune thyroid diseases. (Knezevic 2020) A contributing factor that may be underlying the gut-thyroid relationship is dysbiosis. 

The gut-thyroid axis 

Dysbiosis is characterized by shifts in microbial composition, with an increase and decrease in particular strains that compromises flora balance and gut mucosa integrity. Mounting evidence suggests that these changes are associated with both hypothyroidism and hyperthyroidism. (Zhao 2018)(Ishaq 2017)(Jiang 2022) While more studies are necessary to determine which specific strains are implicated in the development of thyroid dysfunction, research has broadly demonstrated that reduced bacterial diversity has been found in cases of both hypothyroidism and Hashimoto's thyroiditis. (Cayres 2021)(Jiang 2022)

Numerous studies have indicated that individuals with autoimmune thyroid diseases such as Hashimoto's thyroiditis often exhibit gut dysbiosis prior to the appearance of clinical symptoms. (Lin 2022)(Cayres 2021) This implies that changes in the composition of gut microbiota could serve as a predisposing factor for the development of autoimmune thyroid disorders. (Adapa 2023) 

Emerging studies have provided a preliminary understanding of the gut-thyroid axis, indicating that intestinal microbiota and its metabolites may act directly or indirectly on the thyroid by influencing intestinal nutrient availability, immune regulation, and thyroid hormone regulation. This provides new insights into the pathogenesis of thyroid disorders and sheds light on potential clinical management strategies. (Jiang 2022)

Emerging evidence shows that there's a relationship between the gut microbiome and thyroid health. Understanding this dynamic may be key to optimizing thyroid health. 

Effects of the microbiota on thyroid function

 Intestinal microbiota and their metabolites are diverse and perform various essential regulating functions that can have an impact on thyroid hormone production and metabolism. This relationship manifests through pathways such as host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and thyroid hormone regulation, which are discussed further below. (Dodd 2017)(Round 2009) 

Availability of nutrients

The composition of the gut microbiota influences the availability of essential micronutrients for the thyroid gland. Microbiota influence the uptake of nutrients relevant to the thyroid including iodine, iron, selenium, and zinc. (Knezevic 2020) 

Iodine 

Animal studies suggest that reduced intestinal microbiota may affect radioiodine uptake and thyroid function. (Adapa 2023) Iodine uptake is mainly achieved by the sodium/iodine symporter (NIS) located in the thyroid cells. It's speculated that metabolites of the gut flora, including lipopolysaccharides (LPS) and short-chain fatty acids (SCFAs) released by the gut microbiota, alter the thyroid iodine metabolism by increasing NIS expression and activity. (Nicola 2010)(Velez 2006)(Sponziello 2010) 

Iron 

Microbiota can influence the availability of iron in several ways. Heme iron is an important nutrient for both humans and the intestinal microbiota. It’s directly absorbed by heme/folate transporter 1 in humans and by siderophores like enterobactin in bacteria. (Knezevic 2020) Some pathogenic strains grow well in heme-rich conditions, as they require iron for their virulence and colonization. (Chieppa 2018)(Kortman 2014)(Bullen 2000) These include enteric gram-negative bacteria like Salmonella, Shigella, and pathogenic E. coli. (Kortman 2014)(Bullen 2000) Overgrowths of such strains can therefore hinder iron availability for the host. In contrast, beneficial commensal gut bacteria from the genera Lactobacillus and Bifidobacterium require minimal to no iron. (Weinberg 1997) 

Furthermore, microbiota can enhance iron bioavailability in the colon by lowering the pH through the production of SCFAs. (Knezevic 2020) 

Selenium 

Microbiota have been shown to influence the metabolism of selenium, thereby playing a role in the regulation of thyroid functions. (Jiang 2022) It has been found that Lactobacillus converts intracellular sodium selenite into selenocysteine and selenomethionine, which facilitates the absorption of selenium into the human. (Calomme 1995)(Pessione 2012) Furthermore, there seems to be a positive correlation between several species of Lactobacillaceae and Bifidobacterium with selenium. (Knezevic 2020) This implies that having adequate amounts of these microbiota may help improve the absorption of selenium. 

Zinc 

Microbiota may influence the absorption and utilization of zinc. (Jiang 2022) Research demonstrates that SCFAs produced by microbiota may increase zinc absorption by decreasing luminal pH in the intestines. (Topping 2001) Strains of Lactobacillaceae and Bifidobacterium also demonstrate a positive correlation with zinc. (Knezevic 2020)

Microbiome testing, which involves analyzing the microorganisms present in a stool sample, may help providers gain insight into a patient’s microbiome.

Impact on the immune system

One way the gut microbiota impacts the immune system is that it plays a significant role in maintaining homeostasis and influencing the development of immune cells. There's a direct relationship between the concentration of the SCFA butyrate and the population of regulatory T-cells, which is crucial for immune tolerance. (Kohling 2017)(Asarat 2016)(Knezevic 2020) 

Immune tolerance refers to the ability of the immune system to recognize and tolerate the body's own cells and tissues as "self," distinguishing them from foreign invaders or harmful substances. It's a fundamental aspect of immune function that prevents the immune system from attacking healthy tissues and causing autoimmune diseases. 

Another way that gut flora can impact the immune system is through antigenic cross-reactivity between gut microbiota and the thyroid. Normally, SCFAs can strengthen intercellular tight junctions together with thyroid hormones, which helps maintain the integrity of the intestinal wall. (Frohlich 2019)(Knezevic 2020) Once the intestinal barrier is compromised (e.g., due to dysbiosis), the increase in intestinal permeability allows antigens to pass more easily and activate the immune system or cross-react with extraintestinal tissues. (Knezevic 2020) Cross-immune reactivity has been induced by several strains with substances structurally similar to thyroid peroxidase (TPO). (Wang 2010)(Kiseleva 2011)(Bassi 2010) Cross-immune responses such as these can trigger potentially increased autoimmunity.

Impact on thyroid hormones

Gut microbiota play a role in thyroid hormone production and metabolism in several areas. Potential key pathways are outlined below.

Binding of thyroid hormone and peripheral conversion

Gut microbiota play an important role in thyroid hormone metabolism as they produce enzymes such as iodothyronine-deiodinases, which are involved in the peripheral conversion of thyroxine (T4) to its active form triiodothyronine (T3) or reverse T3 (rT3), its inactive form. (Adapa 2023)(Frohlich 2019) Animal research has shown that gut bacteria are indeed involved in the binding of thyroid hormones and even compete with albumin. (Virili 2018)(Nguyen 1993)(Knezevic 2020) There’s evidence that reduced microbiota affect thyroid hormone binding ability in the gut. (DiStefano 1993) One study found that there was a significant decrease in the binding ability of T3 and T4 in antibiotic-treated rats compared to normal rats. (DiStefano 1993)

Reabsorption of thyroid hormone

Gut microbiota also play an important role in the reabsorption of thyroid hormone as they produce and secrete enzymes with deconjugation activity, such as β-glucuronidase and sulfatase, which allows thyroid hormone to re-enter the enterohepatic circulation. (Fenneman 2023) Studies demonstrate that the microbiota can improve the reabsorption of thyroid hormones in the enterohepatic circulation. (Virili 2017)(Rutgers 1989)

Modulation of thyroid-stimulating hormone

Emerging evidence suggests that signals from gut microbiota through the gut-brain axis could influence the release of thyroid-stimulating hormone (TSH) from the pituitary gland. Higher TSH levels are typically observed in people with gut dysbiosis and lower bacterial diversity. It's theorized that bacterial metabolites and modulation of the vagus nerve might affect TSH secretion. (Knezevic 2020) However, the precise mechanisms through which gut bacteria modulate TSH secretion remain unclear, necessitating further research. (Adapa 2023)

Symptoms and conditions associated with microbiome-related thyroid imbalances

Apart from thyroid autoimmune diseases, dysbiosis can be associated with other gut-related symptoms or conditions, which can point to an underlying microbial imbalance. These can involve inflammation, tight junction integrity, nutrient deficiencies, or gastrointestinal motility issues.

Inflammation

A dysbiosis involving an increase in pathogenic bacteria results in gut inflammation. (Paganini 2017) Additionally, chronic inflammation itself can induce shifts in the microbiota composition by altering the oxidative and metabolic conditions within the intestine. (Frohlich 2019)(Frank 2007) Inflammation may be evident through the clinical presentation of inflammatory conditions such as celiac disease or NCGS. (Biesiekierski 2017) Symptoms can vary and range from gastrointestinal discomfort (e.g., diarrhea, constipation, bloating) to extraintestinal manifestations such as fatigue, anemia, brain fog, and other nonspecific symptoms that may also resemble and overlap with those of hypothyroidism. (Valenti 2017)(Knezevic 2020) Lab markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), which are general markers of inflammation, can also help to identify inflammation.

Weakened tight-junction integrity

Microbial dysbiosis can adversely affect the integrity of tight junctions. (Ma 2022) Weakened tight junctions can lead to larger molecules, such as toxins, undigested food particles, and bacteria, passing through the intestinal lining into the bloodstream and triggering immune responses and inflammation. Food sensitivities can occur as a result of this and may be associated with lower gastrointestinal symptoms such as abdominal pain, bloating, flatulence, altered bowel habits, and other symptoms such as brain fog, fatigue, mood changes, and skin rashes or eczema. (Tuck 2019)(Ong 2010)

Nutrient deficiencies

Microbiota play a role in nutrient absorption and availability. As a result, identifying nutrient deficiencies such as iron, selenium, or zinc may indicate enhancement of the microbiome as a target of treatment.

Constipation/motility issues

Since intestinal bacteria play a role in the digestion of dietary fibers and production of SCFA that contribute to gut health, decreased transit time could point to potential dysbiosis as gut microbes impact gut transit time. (Knezevic 2020)(Shin 2019) This relationship is evident as supplementation with probiotics has been found to improve functional constipation. (Mitelmão 2022) In addition, an irregular gut transit could also promote dysbiosis by promoting the growth of specific bacterial taxa or affecting bacterial colonization. (Shin 2019)

Microbiome testing

Microbiome testing is a method for gaining more insight into a patient’s microbiome. It involves analyzing the microorganisms present in a stool sample. The human gut microbiome, in particular, is a diverse community of bacteria, viruses, fungi, and other microbes that play a crucial role in digestion, immune function, and overall health. Here’s how microbiome testing through stool typically works: 1. Sample collection: The individual collects a small stool sample using a collection kit provided by a healthcare provider or a testing company. The sample is usually collected at home and then sent to a laboratory for analysis. 2. DNA extraction: Although some samples might be cultured for analysis, many lab companies use DNA extracted from the stool sample. This DNA, which contains genetic material from the various microorganisms in the gut, is used to identify the species present. 3. Sequencing: Advanced sequencing techniques, such as quantitative polymerase chain reaction (qPCR) technology, are used to analyze the DNA extracted from the stool sample. This process allows scientists to identify and quantify the different types of microorganisms present, such as bacteria (e.g., Firmicutes, Bacteroidetes), viruses, fungi, and even parasites. 4. Analysis and interpretation: The sequencing data is then analyzed using bioinformatics tools and databases. This analysis provides insights into the composition of the gut microbiome, including the diversity of species present, their relative abundance, and potential functional characteristics. 5. Reporting: The results are compiled into a quantitative report for use by the healthcare provider. Reports meant for providers provide interpretive reference ranges to help clinicians use the data to inform their patient plan. Microbiome testing is a rapidly evolving field with applications in both research and clinical settings. It offers a deeper understanding of the complex interactions between human health and the microbiome.

Managing the gut-thyroid relationship

Improving the gut microbiome may help support thyroid function. Several factors can affect the gut microbiome and may be considered in the management of thyroid dysfunction.

Fiber

Increasing fiber intake can help improve gut bacterial diversity, promote the growth of beneficial bacteria, and restrict the growth of pathogenic species. (Knezevic 2020)(Du 2023) Consumption of fiber can improve thyroid hormone levels and reduce thyroid antibodies in patients with autoimmune thyroid disease. (Huo 2021)

Saturated fat

High saturated fat intake is associated with unhealthy changes in the gut microbiota. (Elbaz 2021) Limiting saturated fats, such as red meat, full-fat dairy, and processed foods, may help improve thyroid function.

Fermented foods

Consuming fermented foods such as yogurt, kimchi, sauerkraut, and miso can help improve the microbiome, as fermented foods contain live beneficial bacteria that can contribute to a healthy microbiome. (Huo 2021)(Elbaz 2021)(Khogali 2023)

Sugar

High-sugar diets can cause dysbiosis by promoting pathogenic bacteria. Additionally, insulin resistance and inflammation caused by high sugar intake are risk factors for thyroid disease. Limiting intake of sugar, such as sweets and soft drinks, may help to promote thyroid health. (Ramezani 2022)

Stress management

Stress has been associated with alterations in gut microbiota, which can contribute to impaired thyroid function. (Ramezani 2022) Reducing stress through activities like exercising, meditating, and seeking social support can help to improve thyroid function.

Supplementation

Supplementation of probiotics shows beneficial effects on thyroid hormones and thyroid function. (Knezevic 2020) In hypothyroidism and hyperthyroidism, Lactobacillaceae and Bifidobacteriaceae strains are often reduced, and these are generally considered beneficial bacteria. (Knezevic 2020)(Jiang 2022) Probiotics containing these species may increase thyroid hormone levels, decrease thyroid antibodies, and reduce inflammation in autoimmune thyroiditis. (Huo 2021) Synbiotic supplementation, a combination of probiotics and prebiotics, has shown beneficial effects on patients with hypothyroidism by significantly increasing free T3 and reducing TSH, levothyroxine dose, and fatigue. (Talebi 2020) However, the evidence supporting the thyroid-related advantages of prebiotics and probiotics is currently sparse and inconsistent. Larger-scale trials are necessary to validate their effectiveness and determine optimal strains and dosages. (Adapa 2023)

The bottom line

It’s evident that our gut microbiota play a role in our thyroid function through various pathways. From a nutritional perspective, they can influence the metabolism and absorption of certain nutrients that are necessary for thyroid health. They play a role in immune regulation, which can increase the risk of autoimmune thyroid disease. Gut microbiota also directly contribute to the regulation of thyroid hormones. These findings emphasize the significance of the gut microbiome as a potential therapeutic target for a comprehensive approach to managing thyroid disorders.