Gut & Diet

Hyaluronic Acid benefits in the gut.

The benefits of a healthy gastrointestinal system extend beyond the gut to our overall well-being and health (Jiang, et al., 2011). Gut homeostasis is central to hydration, gut microbiome, and innate immunity (Salem, et al., 2018; Colgan, 2013; de la Motte, 2011; de la Motte & Kessler, 2015; Galland, 2014; Kim & de la Motte, 2020). Hyaluronic Acid promotes gut health by improving hydration, maintaining a healthy gut microbiome, and leading to overall feelings of well-being by decreasing stiffness and pain (Bellar, et al., 2019; de la Motte & Kessler, 2015; Fallacara, et al., 2018; Gupta, et al., 2019). Oral Hyaluronan acts both in the gut as well as being absorbed into the blood to be distributed to the body (Fallacara, et al., 2018), where HA also has positive effects in addition to those in the gut.

There is evolving evidence that HA plays a role in the gut-skin-brain axis (Salem, et al., 2018; Galland, 2014). The gut-brain-skin axis occurs because all these organ systems work together. Therefore, poor health of one system reduces the health of the other two systems. For example, there is some evidence that chronic fatigue syndrome, which is characterized by extreme tiredness, mental “fogginess”, and a generally ill appearance, might be caused by gut microbiome bacteria that enter the blood stream when the gut wall becomes too leaky. HA might be beneficial to support and improve the gut-brain-skin axis because HA contributes to a non-leaky gut, which prevents cells and chemicals from escaping into the blood (de la Motte & Kessler, 2015; Galland, 2014; Kim et al., 2018)



In the immune system section, we described how COVID-19 ARDS (Acute Respiratory Distress Syndrome) resulted from excess Hyaluronic Acid in the lungs, and retaining excess water ultimately leading to the lungs being unable to transport oxygen across the tissue support layer to blood. This was an example of too much HA and too much water. However, the situation in the eye is exactly the opposite. Extra HA, in the form of sterile HA drops, added to eyes helps retain water in the eyes to relieve dry eye conditions. Later in the book, we will discuss HA in eyes in more detail.

In the gastrointestinal tract, the ability of HA to soak up water is required for health. In the gut, HA soaks up water and stores it until the body starts to run low on water. Then, HA starts to release its stored water. The support layer for gut cells, especially, requires the water-storing ability of HA to perform its role in gut and overall body health (de la Motte, 2011; de la Motte & Kessler, 2015; Kim & de la Motte, 2020). Most of the water absorbed into the body is absorbed from the gut. This water is then transferred to other parts of the body where it improves body function (Bellar, et al., 2019; de la Motte & Kessler, 2015; Fallacara, et al., 2018; Gupta, et al., 2019), including improving the look and feel of skin (Göllner, et al., 2017). The water absorbed into the gut support layer also assists in transporting ions and nutrients from the gut into the blood (de la Motte, 2011). Finally, a well-hydrated gut tissue support layer maintains the integrity of the gut so that pathogens can’t gain entrance to the body and ensures that the immune functions of the gut occur normally (de la Motte, 2011; de la Motte & Kessler, 2015; Kim & de la Motte, 2020).


There is preliminary evidence that HA can stabilize and modulate the gut microbiome. A human clinical trial found that topical HA gel helped to maintain healthy microbiome in the mouth after dental implant surgery (Soriano-Lerma, et al., 2019). A clinical study in healthy people found that low molecular weight HA did not change the composition of the gut microbiome; however, this study did not look at high molecular weight HA, unhealthy humans, or humans with disturbed microbiomes (Bellar, et al., 2019). In mice that had experimental intestinal inflammation, a conjugate HA drug, in which HA was linked to another molecule, reversed the effects of inflammation both on the structure of the gut and on the general well-being of the mice. Part of this effect was due to promoting a healthy microbiome in the mice (Lee, et al., 2020).


In an earlier section, we talked about the role played by HA in regulating innate and adaptive immunity. A main site where immune processes occur is in the intestinal lining (de la Motte, 2011; de la Motte & Kessler, 2015; Kim & de la Motte, 2020). HA is known to bind to the surfaces of gut immune cells to modulate their functions both in health and illness (de la Motte & Kessler, 2015). In mice, there are indications that HA’s actions in the gut might be linked to preventing inflammation (Lee, et al., 2020).

Crohn’s Disease is chronic inflammation of the gut. You might remember from our discussion of innate immunity earlier in the book, that one way the innate immune system sends out an alarm that there is an invader is by breaking down high molecular weight HA into HA fragments that act to attract innate immune cells. In Crohn’s Disease, it appears that the normally healthy balance between building and breaking down HA is subverted to cause illness. Intestinal cells isolated from people with Crohn’s Disease expressed excess amounts of a specific protein. One of the illness-causing actions of that protein is to break down high molecular
weight HA into fragments inappropriately (Sorosh, et al., 2016). Just like in the innate immune system, these HA fragments called cells that contribute to inflammation to the gut; except, in this case, there is no need for those cells to come to the gut because there is no invader to which to respond.

In the next section, we will discuss how HA might affect longevity. We will use the story of Yuzurihara in Japan to illustrate a possible mechanism by which HA primes our bodies to live long, cancer-free lives.