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What Are Lipopolysaccharides, And How Can They Affect Thyroid Health?

Lipopolysaccharides (LPS) are referred to as endotoxins, and they are large molecules found in gram-negative bacteria.  Although most people with thyroid and autoimmune thyroid conditions have never heard of lipopolysaccharides, these can have a profound effect on one’s health.  This is especially true for those people with Graves’ Disease and Hashimoto’s Thyroiditis, although they can also affect those with non-autoimmune thyroid conditions.

LPS are the major components of the cell wall of gram-negative bacteria (1) [1].  Under normal circumstances they protect the cell membrane.  However, when a gram-negative bacteria dies, the LPS of this bacteria is released.  LPS can cause numerous biological effects, such as fever, leukocytosis (high number of white blood cells), iron deficiency, platelet aggregation, thrombocytopenia, and blood clotting disorders (2) [2].  LPS from gram-negative bacteria is one of the most potent innate immune-activating stimuli known.  An alteration in the LPS response may play a role in the pathogenesis of a number of inflammatory diseases (3) [3].

The Role of LPS In Autoimmunity and Leaky Gut Syndrome

Lipopolysaccharides can lead to an increase in intestinal permeability, also known as a leaky gut (4) [4] (5) [5].  I’ve spoken about the relationship between leaky gut syndrome and thyroid autoimmunity in other articles and blog posts.  There are numerous factors which can cause a leaky gut, and lipopolysaccharides are one of these factors.  So having high levels of LPS can increase one’s chances of developing a leaky gut, and this in turn can increase one’s chances of developing Graves’ Disease or Hashimoto’s Thyroiditis.

The company Cyrex Labs has an intestinal permeability test that measures the antibodies against LPS.  When this shows positive findings for LPS it usually means that there has been infiltration through the intestinal barrier into the systemic circulation.  In other words, there will be the presence of lipopolysaccharides in the bloodstream, and the person will usually have an increase in intestinal permeability (a leaky gut).  However, I’ve had some patients test positive for LPS antibodies on a Cyrex Labs test, but not show any signs of hyperpermeability.

For those who aren’t familiar with Cyrex Labs, their Intestinal Antigenic Permeability Screen tests for the presence of three types of antibodies that are associated with an increase in intestinal permeability.  These include the Actomyosin antibodies, the Occludin/Zonulin antibodies, and the Lipopolysaccharides (LPS).  Both the Actomyosin and Occludin/Zonulin antibodies directly relate to the presence of a leaky gut.  So in other words, if either of these two antibodies are outside of the normal range then this indicates that someone has a leaky gut.

However, the presence of LPS alone doesn’t necessarily indicate that someone has a leaky gut.  The presence of LPS does indicate intestinal dysbiosis (an imbalance of the gut flora), and dysbiosis is commonly associated with a leaky gut.  As a result, if someone does the Cyrex Labs test and has a positive test for LPS, but both the Actomyosin and Occludin/Zonulin antibodies are negative, then this means the person has intestinal dysbiosis in the absence of a leaky gut.  Of course this is assuming the person doesn’t have suppressed immunoglobulins, which can result in a false negative on the Cyrex Labs test and is something to be aware of.

What Are The Causes Of Elevated LPS?

Remember that lipopolysaccharides are endotoxins which are found in gram-negative bacteria, and that LPS is released when a gram-negative bacteria dies.  When someone has high levels of LPS this is associated with intestinal dysbiosis.  And there are numerous causes of intestinal dysbiosis, and some of the more common causes include antibiotics, chronic stress, and food allergens (6) [6].

LPS and Thyroid Health

LPS can affect thyroid health in numerous ways.  As I have already mentioned, LPS can lead to the development of a leaky gut, which can in turn trigger an autoimmune thyroid condition.  However, there is also evidence that LPS can suppress the hypothalamic-pituitary-thyroid axis (7) [7].  Remember that the hypothalamus produces thyrotropin-releasing hormone (TRH), which stimulates the pituitary gland to secrete TSH, which in turn signals the thyroid gland to secrete thyroid hormone.  A more recent study shows that LPS can downregulate pituitary and thyroid function (8) [8].  In addition to decreasing TSH secretion, it also affects secretion in follicular cells directly (8) [8].  In other words, LPS can decrease thyroid function not only by affecting the pituitary gland, but also by directly affecting the cells of the thyroid gland.  However, while it seems to result in a decrease in thyroxine (T4), it doesn’t seem to decrease the conversion of T4 to T3.

In summary, lipopolysaccharides are large molecules found in gram-negative bacteria, and they are elevated in intestinal dysbiosis.  LPS activate the innate immune system, and can lead to the development of inflammatory conditions, as well as a leaky gut.  This can in turn trigger an autoimmune response, leading to a condition such as Graves’ Disease or Hashimoto’s Thyroiditis.  There is also evidence that LPS can suppress the hypothalamic-pituitary-thyroid axis.