I feel like today’s article could be renamed as “a few of my favorite things”! We are jamming on the thyroid, inflammation, detox pathways, gut health, estrogen and how all of these factors interact. Throughout my years of learning about the thyroid I was never quite satisfied with the understanding that it was mainly stress and undernutrition that affected the thyroid. Everyone focused on how the thyroid gland worked, which is critical, don’t get me wrong. But if we do not convert our hormone properly, or allow it to interact with the receptors properly, then your thyroid can work as hard as it wants to but you may still not feel at your best. This is where it becomes critical to understand how your gut affects your thyroid.
Thyroid Hormone Conversion
It is often quoted in the blogosphere that upwards of 20% of your thyroid hormone is converted, or activated in your gut. Although I have not been able to find that specific resource, we do know that the gut plays an important role in thyroid hormone conversion.
Without getting too too technical here, I think it is incredibly important to remember that our body is smart! For every hormone that is made there are multiple buffering systems in place to try to ensure that we have the right amount. There are multiple breakdown pathways and rescue pathways to get more out of our bodies, or to increase our absorption, respectively. Thyroid hormone is no exception to this rule!
After we make T4 we have multiple conversion options, we can take off the outside iodine, making T3, or take off the inside iodine, making rT3. Additionally, we have liver detoxification pathways that help to break down and eliminate thyroid hormone, these are known as sulfation and glucaronidation. Sulfation and glucaronidation essentially allow hormones, and other compounds, to be more water soluble so that they can be eliminated in the urine and the bile (or poop)1.
“….a cycle of having no energy, weight gain, brain fog and digestive issues that can be stubborn to break, even with thyroid hormone.”
Why is this important?
When our body has an increased need for thyroid hormone our gut bugs come to the rescue! As T3 sulfate strolls by, tagged for elimination, certain gut bugs can step in and break off the sulfate component, allowing the thyroid hormone to re-enter circulation. The same is true for glucaronidation. Our bacteria have enzymes, known as B-Glucaronidase, this enzyme will free up thyroid hormone once again so that it can re-enter our body and exert the needed actions on our cells1.
Even with all of these systems in place we still excrete thyroid hormone every day! That number of course will depend on how much you are making, and how much more your body needs that day!
LPS and Thyroid Receptor Sites
Inflammation sits at the base of the pyramid of almost every case of thyroid disease that I have seen. Interestingly, I have also seen that many patients seem to be caught in a loop when it comes to hypothyroidism and inflammation. A cycle of having no energy, weight gain, brain fog and digestive issues that can be stubborn to break, even with thyroid hormone. Naturally this pattern led me to look further into the research, for a piece of the puzzle that could fit these symptoms together. The research that I found was interesting! (Keep in mind that much of the mechanistic research here was done in animals, but given some human research, and my clinical observations, it is enough to talk about!)
“Essentially, inflammation and the thyroid are NOT friends, and almost every aspect of thyroid functioning and signaling can be affected by LPS and inflammation.”
LPS, or lipopolysaccarhide, is an inflammatory component that exists on certain types of bacteria (gram negative bacteria). This is to protect them, but when it gets into our blood stream it can cause significant systemic inflammation. We now know that LPS also has a direct effect on the thyroid as well. The studies on this show a variety of different mechanisms, although the one that seemed to have a common thread throughout was regarding its effects on TSH and the TSH receptor.
In states of significant stress, or inflammation, we can see euthyroid sick syndrome, which is a condition where you have low levels of T3, T4 and normal or low levels of TSH2,3. Put simply, this is because the body down regulates its metabolism to protect us from the stress of illness. Not all LPS and thyroid interactions are this easy to pick up in the lab work though3. Some studies also suggest that our bodies ability to respond to TSH is decreased by LPS production, and therefore we have to scream at the receptor with TSH.
Inflammation can also cause a decrease in our ability to convert T4 into T3 in the periphery, decreasing the amount of active hormone circulating. This combined with the fact that it has been suggested to increase thyroid –binding-globin, which acts as a bus, carrying thyroid hormone around inactive, further closes the loop on the potential to feel thyroid healthy with LPS/ inflammation present2.
On another note, research has also suggested that LPS can increase the risk of thyroid autoimmunity, specifically anti-TPO (see Thyroid 101 for more information on this). This has a whole host of other downstream effects, outside of the scope of this article, but something to be noted none the less4.
Essentially, inflammation and the thyroid are NOT friends, and almost every aspect of thyroid functioning and signaling can be affected by LPS and inflammation. The gut MUST be addressed when dealing with the thyroid.
T4 and Inflammation
In the previous paragraph we spoke about the thyroid- inflammation loop. In addition to coming to understand how LPS and inflammation can affect the communication with your thyroid hormone receptors, thyroid hormone itself has an impact on inflammation. Preliminary research suggests that T4, the ‘storage form’ of your thyroid hormone, can decrease inflammation in the gastrointestinal tract. In the presence of T4, intraepithelial lymphocytes (IEL =white blood cells in the intestinal lining) were decreased in animal models5. Although this hasn’t been repeated in humans, we do know that IELs are increased in Hashimoto’s disease6, and also have a significant role to play in Graves disease7. More research is needed in this area, but it is enough to allow me to believe that we cannot focus on just the thyroid hormone OR gut inflammation. Both aspects are critical and should be addressed. And one major way to do that is listed below!
Summary thus Far
Some gut bacteria contain LPS which is an inflammatory component. When in the body LPS can decrease the conversion of T4 to T3, increase TBG and decrease how well your TSH receptor listens to the signal of TSH. Additionally, LPS and gut inflammation can increase your risk of autoimmunity!
We cannot forget the importance of having hormones present though, as T4 may help to stabilize gut inflammation.
We need a good gut bacterial balance AND sufficient levels of thyroid hormones to have a healthy thyroid hormone balance.
An anti-inflammatory diet can also be helpful!
Gluten, Leaky Gut and the Thyroid
Although this could be dedicated to an article topic all its own, we must also consider that gluten has been shown to affect the gut thyroid axis via increasing intestinal hyperpermeability. Gluten individually has the capacity to increase a protein known as zonulin. Zonulin acts in the intestines like the buttons on a shirt. It keeps the intestinal lining intact. When zonulin increases in the blood stream it is a sign that the buttons are popping off, and the intestinal barrier is becoming, “leaky” or permeable. This can predispose individuals to autoimmune disease, which is one of the main causes of thyroid disease (both hyper and hypothyroidism).
Although there are many factors that increase intestinal hyperpermeability, gluten is an every day example of how what we eat affects gut-thyroid axis.
Intestinal hyperpermeability is also responsible for a significant amount of LPS being permitted to enter into circulation, and causing the issues discussed earlier in the article.
Thyroid Binding Globulin and Estrogen Levels
Finally, yet another mechanism through which the gut affects the thyroid, and thyroid hormone activity in our bodies, is through the guts role in other hormone disposal.
Estrogen is a reproductive hormone that is made in both men and women, although the ladies make much larger amounts! When circulating in elevated levels estrogen has been shown to increase thyroid binding globulin, or TBG8. We discussed TBG above, referring to it as a bus that carries around and inactivates thyroid hormones. So when TBG is circulating in larger amounts, there are more busses to pick up and hold your thyroid hormones hostage, definitely not ideal! This is why some people can have high-normal total T3 but low levels of Free T3, the hormone that acts on the cells.
So how is the gut involved in this action?
Similar to thyroid hormones estrogen goes through the detoxification pathways, glucaronidation and sulfation, to be made more water soluble. These then go into the bowel, and in theory should be eliminated in your poop BUT how many of you are actually pooping properly? Constipation is a massive issue, not only in people with hypothyroidism, but also in the general population. We should be having at least one, if not two to three, bowel movements per day to eliminate all of the hormones and other junk from our bodies. When this doesn’t happen, and in the face of increased levels of B-Glucaronidase containing bacteria, we will increase the recirculation of estrogen, therefore potentially increasing TBG levels in the body. Double negative!
Pooping properly, regularly and balancing out your gut flora is critical for estrogen levels, healthy detoxification of the body, your mental health and also proper thyroid function!
Just Start
Now you have an overview as to why we MUST consider the gut when treating thyroid conditions. When we are inflamed, our detox capacity overwhelmed, when we are not properly pooping, not balancing our gut bugs and not being conscious of our diet, we will not feel at our best. Period. I know this sounds like a lot to consider, but it is crucial to better understanding why your body is not working properly.
I do not want to overwhelm you today by getting into the nitty gritty of gut treatments, because that is an article, or four, all its own! If you are feeling motivated by this information then I urge you to do two things.
1) Let me know on Facebook, what are your biggest thyroid concerns? What are your biggest obstacles?
2) Get tested! I am a huge advocate of what you don’t know, you can’t address. Whether this is stool testing, basic inflammatory testing, or even just a thorough thyroid panel, take one step today to start figuring out why you are feeling so crappy and start to address it!
References
- Peeters, R. P. & Visser, T. J. Metabolism of Thyroid Hormone. (2012).
- Kunc, M., Gabrych, A. & Witkowski, J. M. Microbiome impact on metabolism and function of sex, thyroid, growth and parathyroid hormones. Acta Biochim. Pol. 63, 189–201 (2016).
- Boelen, A. et al. Simultaneous changes in central and peripheral components of the hypothalamus-pituitary-thyroid axis in lipopolysaccharide-induced acute illness in mice. J. Endocrinol. 182, 315–23 (2004).
- Nazar, M., Nicola, J. P., Vélez, M. L., Pellizas, C. G. & Masini-Repiso, A. M. Thyroid peroxidase gene expression is induced by lipopolysaccharide involving nuclear factor (NF)-κB p65 subunit phosphorylation. Endocrinology 153, 6114–25 (2012).
- Wang, J., Klein, J. R. & Hardy, R. R. Hormone regulation of murine T cells: potent tissue-specific immunosuppressive effects of thyroxine targeted to gut T cells. Int. Immunol. 8, 231–235 (1996).
- Cindoruk, M. et al. Increased colonic intraepithelial lymphocytes in patients with Hashimoto’s thyroiditis. J. Clin. Gastroenterol. 34, 237–9 (2002).
- Paschke, R. et al. Regional stimulation of thyroid epithelial cells in Graves’ disease by lymphocytic aggregates and plasma cells. Acta Endocrinol. (Copenh). 125, 459–65 (1991).
- Pedersen, C. et al. Late pregnancy thyroid-binding globulin predicts perinatal depression. Psychoneuroendocrinology 65, 84–93 (2016).
