The Mystery of Mucus and the Microbiome - September 2023

The Mystery of Mucus and the Microbiome - September 2023

By Andrea McBeth 

When we think about the components of our body that keep us healthy, we often overlook one unsung hero: mucus. This sticky substance, which can be found lining various surfaces of our body including our nose, lungs, and digestive tract, plays a crucial role in protecting our health. It is so much more than just our childhood boogers. Its function goes beyond a tool to torment our siblings. Erica Sonnenburg a prominent microbiologist at Stanford refers to the mucus layer in the gut as part of a system where “good fences make good neighbors” alluding to the important role the mucus layer plays in helping us coexist with the living organ system that is our microbiome. 

The mucus layer in our gut provides a unique environment where an intricate dance between human cells, a variety of microorganisms, and food breakdown particles takes place. This dynamic interaction influences not only our digestive health but also impacts various other aspects of our wellbeing, from our immune response to our mental health. 

What is mucus?

When we think about mucus, it's easy to forget that this complex substance has a long evolutionary history. In fact, the mucus layer is a marvel of biological engineering that has been fine-tuned over hundreds of millions of years, tracing its origins back to organisms as ancient as coral. Just as coral reefs provide a protective and nourishing environment for diverse marine life, our mucus layer does the same for the trillions of microbes that inhabit our gut.

The mucus layer is a complex composition of myriad elements, each playing a unique role in maintaining the health and balance of our bodies. This layer is primarily composed of water, which makes up about 95% of its composition, and mucins, high molecular weight glycoproteins called mucins produced by goblet cells. Together, these components give mucus its distinctive gel-like consistency, allowing it to serve as a protective barrier and lubricant.

However, the mucus layer is far more than just a physical barrier. It's a dynamic environment teeming with life and activity. Electrolytes present in the mucus layer play a crucial role in maintaining the pH balance and ion concentration, supporting the optimal functioning of enzymes and cells within the layer. Lipids, such as phospholipids, enhance the barrier function of mucus by increasing its hydrophobicity, thereby repelling potentially harmful water-soluble substances. In addition, mucus contains a variety of other proteins, including enzymes that aid in digestion, antibodies that provide immune defense, and antimicrobial peptides that ward off pathogenic microorganisms. Shed epithelial cells and immune cells within the mucus layer further contribute to its protective role. Amidst these components, a diverse array of microorganisms thrive, forming the gut microbiota that plays a fundamental role in our health and disease. This complex composition is critical for the various functions that mucus performs, from acting as a physical barrier against pathogens to facilitating the transport of nutrients and waste products.

Mucins, the primary structural components of mucus, are unique due to their specific chemical properties. They are large, heavily glycosylated proteins, meaning they're studded with carbohydrate chains which love water. This allows mucins to retain water, making mucus hydrated and gel-like. Mucins are also flexible and can form a network with viscoelastic properties, meaning mucus behaves both as a liquid and a solid, giving it a slippery yet sturdy nature. Furthermore, mucins carry an overall negative charge, aiding in the spreadability of mucus, and they can self-assemble into larger structures, enhancing the protective barrier properties of mucus. All these features contribute to mucus being an effective protective and lubricating layer in our bodies. Moreover, these mucin sugar chains serve as a food source for some of our gut bacteria, particularly when dietary fiber is scarce. In this way, the mucus layer not only provides a uniquely flowing physical barrier but also contributes to maintaining a healthy and balanced gut microbiome.

Interestingly, different types of mucins are produced in different areas of the body, each tailored to the specific needs of that area. For example, the mucus in our lungs contains a different type of mucin than the mucus in our gut, reflecting the different roles and challenges in these environments.

Maintaining the health and integrity of this complex layer requires adequate hydration and a diet rich in fiber. Without sufficient water, the mucus layer can become thick and less effective, while a diet lacking in fiber can disrupt the balance of our gut microbiota and potentially put our mucus layer at risk.

Our Diet and Mucus

We know that fiber and a variety of fruits and vegetables are important to a healthy diet for many reasons. The foods we eat not only nourish us, but also provide critical sustenance for the trillions of microorganisms that inhabit our gut microbiome. Dietary fiber, in particular, plays a pivotal role in maintaining a healthy gut ecosystem. However, when dietary fiber is scarce, some gut bacteria switch to another source of nutrition: the glycans in our mucus layer. Although this is a normal part of the gut ecosystem's balance, problems can arise if the mucus layer is overly exploited due to a chronic lack of dietary fiber.

A persistent fiber-deficient diet can lead to a situation where gut bacteria over consume the mucus. This can thin out the mucus layer, bringing the bacteria into closer contact with the gut lining, or epithelium. This scenario is one of the underpinnings of gut dysbiosis, an imbalance in the gut microbiota, resulting in inflammation of the gut lining, a common characteristic of many gut disorders. Conditions such as colitis and 'leaky gut syndrome' have been linked to such an inflammatory state and are often associated with diets low in fiber, like the Standard American Diet. Therefore, a fiber-rich diet is not only crucial for our overall gut health, but it's also key to maintaining a healthy mucus layer and a balanced gut microbiota. 

Goblet Cells

Just as skilled craftsmen painstakingly shape beautiful pieces of pottery, certain cells in our body meticulously produce the mucus that lines our gut. These cells, known as goblet cells due to their goblet or wineglass shape, are scattered throughout our gut lining, or epithelium. Their primary job is to produce mucins, the major building blocks of mucus. 

However, the function of goblet cells extends beyond just mucus production. These cells are critical players in our immune response, producing and secreting a variety of substances that help maintain gut health. One of these substances is a small protein called trefoil factor 3 (TFF3), which helps maintain the integrity of the mucus layer and promotes the repair of the gut epithelium after injury.

Goblet cells also secrete chemokines like CCL20, signaling proteins that attract immune cells to sites of potential harm. Moreover, they contribute to the immune response by producing antimicrobial peptides, small proteins that can directly kill harmful bacteria.

In addition to these roles, goblet cells have the ability to present antigens, pieces of pathogens, to immune cells. This helps stimulate an active immune response, making goblet cells not just the craftsmen of the mucus layer, but also active participants in the defense of our gut.

What's fascinating is that the work of goblet cells is influenced by a variety of factors, including signals from other cells, the presence of food and bacteria, and even our own nervous system. For instance, our vagus nerve, part of our parasympathetic nervous system, can stimulate goblet cells to produce more mucus, highlighting the intricate connections between different systems in our body.

Gut-Brain-Mucus Axis

Our mucus layer plays an essential role in the intricate interplay between our gut and brain, acting as the physical barrier and nutrient source in this crucial dialogue. At the center of this conversation is the vagus nerve, the longest cranial nerve that serves as the information highway between the brain and gut.

The vagus nerve, part of our "rest and digest" parasympathetic nervous system, influences mucus production. It can stimulate goblet cells to produce more mucus, reinforcing the gut's protective barrier. Modern tools like sleep trackers, which monitor heart rate variability (HRV), can provide insights into our vagus nerve function and, by extension, potentially our mucus production. 

However, this dialogue isn't a one-way street. It's bi-directional, with signals also flowing from the gut back to the brain. This feedback is facilitated by neuropod cells, specialized gut cells that extend long 'pods' into the gut lumen to sample its contents, including the mucus layer and its resident microbes.

When the mucus layer is compromised, such as when dietary fiber is scarce and gut bacteria resort to consuming the glycans in our mucus layer, these neuropod cells can sense the ensuing imbalance or dysbiosis. This can result in stress signals being sent to the brain, which can influence our mood, stress levels, and even our behavior.

This bi-directional communication can turn into a vicious cycle. Stress signals from the brain can exacerbate gut dysbiosis, leading to a thinner mucus layer and more stress. This cycle underscores the critical importance of maintaining a healthy mucus layer and gut microbiota for both our gut health and mental wellbeing. Breaking this cycle requires supporting our gut microbes to maintain a healthy mucus layer.

Postbiotics and Mucus

In our exploration of the mucus layer and its pivotal role in the gut-brain dialogue, one emerging field of research offers promising avenues for supporting this critical ecosystem: postbiotics.

Postbiotics are beneficial compounds produced by live bacteria during the fermentation process. These include metabolic byproducts such as short-chain fatty acids (SCFAs), vitamins, amino acids, and other bioactive compounds. They are the end result of the fermentation process and, unlike probiotics and prebiotics, are not dependent on the survival of the producing bacteria.

Among postbiotics, SCFAs, particularly butyrate, propionate, and acetate, have been recognized for their potential health benefits. Butyrate, for instance, not only fuels our gut cells but also stimulates goblet cells to produce more mucus, reinforcing our gut's protective barrier. Moreover, butyrate and propionate have been shown to have anti-inflammatory effects and can regulate gene expression through their action as histone deacetylase inhibitors, potentially influencing our health at a cellular and molecular level.

Interestingly, the mucus layer plays a key role in facilitating the interaction between these postbiotics and our gut lining. It acts as a selective barrier, designed to keep whole microbes away from our gut epithelial cells while allowing smaller molecules, like postbiotics, to pass through. This allows the bioactive compounds to interact with our epithelium, immune cells, and neuropod cells, influencing our gut health and beyond.

Concluding this exploration of mucus and the microbiome, we find that our understanding of health is ever evolving. Much like the coral reefs, our mucus layer serves as a complex ecosystem, providing a protective yet nurturing environment for our body's functions. This intricate network, which includes our diet, gut microbiota, and even the bi-directional communication with our brain, underscores the complexity and beauty of our body's inner workings. As we continue to unravel the mysteries of the mucus layer, we are reminded of how interconnected all aspects of our health truly are, leading us to new pathways for maintaining and enhancing our wellbeing. Through supporting our body's natural defenses, like the mucus layer, and nurturing our gut microbiota with a fiber-rich diet and beneficial postbiotics, we can strengthen our body's resilience and promote health from within.



Birchenough, G. M. H., Johansson, M. E. V., Gustafsson, J. K., Bergström, J. H., & Hansson, G. C. (2015). New developments in goblet cell mucus secretion and function. Mucosal Immunology, 8(4), 712–719.

Cook, L., Stahl, M., Han, X., Nazli, A., MacDonald, K. N., Wong, M. Q., Tsai, K., Dizzell, S., Jacobson, K., Bressler, B., Kaushic, C., Vallance, B. A., Steiner, T. S., & Levings, M. K. (2019). Suppressive and Gut-Reparative Functions of Human Type 1 T Regulatory Cells. Gastroenterology, 157(6), 1584–1598

Desai, M. S., Seekatz, A. M., Koropatkin, N. M., Kamada, N., Hickey, C. A., Wolter, M., Pudlo, N. A., Kitamoto, S., Terrapon, N., Muller, A., Young, V. B., Henrissat, B., Wilmes, P., Stappenbeck, T. S., Núñez, G., & Martens, E. C. (2016). A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility. Cell, 167(5), 1339–1353.e21.

Herath, M., Hosie, S., Bornstein, J. C., Franks, A. E., & Hill-Yardin, E. L. (2020). The Role of the Gastrointestinal Mucus System in Intestinal Homeostasis: Implications for Neurological Disorders. Frontiers in Cellular and Infection Microbiology, 10, 248.

Luis, A. S., & Hansson, G. C. (2023). Intestinal mucus and their glycans: A habitat for thriving microbiota. Cell Host & Microbe, 31(7), 1087–1100.

Song, C., Chai, Z., Chen, S., Zhang, H., Zhang, X., & Zhou, Y. (2023). Intestinal mucus components and secretion mechanisms: what we do and do not know. Experimental & Molecular Medicine, 55(4), 681–691.

Taherali, F., Varum, F., & Basit, A. W. (2018). A slippery slope: On the origin, role and physiology of mucus. Advanced Drug Delivery Reviews, 124, 16–33.