Intestinal Mucus: The Ultimate Bodyguard for Digestive Immunity
by Tara Zedayko
A summary of Pelaseyed et al, Immunol Rev. 2014 July; 260 (1): 8–20
At DIG Labs, our mission is to help expand access to insights and data. As pet parents ourselves, one of the most frustrating aspects of caring for the health of our pets is the lack of availability of scientifically sound research when it comes to canine health. That’s why, from time to time, we’ll be writing review blogs, where we take a peer-reviewed scientific journal article, and break it down into more manageable bits of information. While you should definitely consult with your veterinarian with any questions or concerns you might have regarding your pet’s health condition, we hope that these tools will help support those conversations.
When thinking of the digestive system, urine and feces are typically the only excrements that come to mind. However, the unsung hero of digestive excrements, mucus, plays a pivotal role by:
· protecting host animals from infection,
· regulating immunity,
· protecting the delicate epithelium from the harsh acids required to break down our nutrients, and more.
In this article, we will deconstruct a pivotal peer-reviewed paper authored by Pelaseyed et al, to shed some light on mucus — how it works, why it’s important, and more.
Mucus — What is it?
Digestive mucus, a secretion comprising > 98% water, can be found in the stomach, small intestine, and colon. In the intestine, mucin type MUC2 is a major component of the mucus, and in the stomach, it’s MUC5AC.
· In the intestine, mucus serves as a coating that limits access to the small intestinal lining.
· In the stomach and large intestine, there are two mucus layers — for the large intestine, the inner layer separates bacteria from the large intestinal lining, and the outer layer is home to the microbiota that reside there.
· The mucus of both the small intestine and the outer layer of the large intestine can both be easily detached.
Mucin is produced by special cells called goblet cells, as well as other special compounds. Mucin is what gives the mucus its gel-like consistency. The mucins have the capability of binding together to form extremely long polymers, comprised of complex carbohydrates. The hydrophilic nature of the mucus provides a physical barrier, a literal diffusion barrier, by binding water among itself.
Mucus — Characteristics
Because of the fleeting properties of mucus, it is really difficult to study in real life. In mice, mucus thickness can approach approximately 0.5mm[i]. Its own dynamic ecosystem, mucus takes time to regenerate when assaulted. Replenishment of new goblet cells and MUC2 biosynthesis, assembly, and accumulation may take more than 4–5 hours. For inner mucus, the renewal can occur every 1–2 hours.
Interestingly, mucus from the small intestine is quite mobile, and tends to follow the peristaltic rhythm as it progresses. This mobility provides an additional deterrent against bacterial invasion, as the bacteria would need to migrate “up and through” the mucus to penetrate it and reach the epithelium.
Furthermore, the properties of the inner mucus layer are not static. Ingested compounds can render the inner mucus penetrable to bacteria virtually immediately. Diseases such as ulcerative colitis demonstrate penetrable mucus as well — allowing proximity of the epithelial lining to an onslaught of bacteria, triggering inflammatory response. Other acute or chronic inflammatory colonic conditions are correlated to a penetrable inner mucus layer.
Mucus — Composition
Upstream from mucins, a main constituent of intestinal mucus is the goblet cell. These cells produce and secrete a variety of proteins that constitute intestinal mucus, including MUC2 which is the structural backbone of mucus. Interestingly, goblet cells also have an important function as “gatekeeper” for helping to determine whether a larger scale immune response should occur. Goblet cells were originally thought to just be a secretory cell. It’s been shown that goblet cells can actually uptake material from the intestinal lumen and deliver it to dendritic cells, which are a major player in eliciting an immune response such as inflammation. Goblet cells work with our immune system to uptake antigen, stimulate secretion, and undergo autophagy, or the cleaning out of dead cells in order to make room for new ones.
Another main component of the intestinal mucosa are enterocytes. These cells are responsible for mediating absorption of ions and nutrients in the small intestine. To do so, enterocytes have an expanded surface made up of villi and glycocalyx that is rich with carbohydrates. The glycocalyx is made up of transmembrane mucins that aid in maintaining the integrity of the intestinal mucus so that pathogens cannot penetrate and invade. Enterocytes also contain a variety of immune signaling molecules that are responsible for recognizing microbial structures to elicit an immune response against invaders. The mucosal system utilizes goblet cells and enterocytes in defense against bacterial, viral, and fungal pathogens.
While goblet cells and enterocytes seem to be the main players in gastrointestinal immunity, there are also subepithelial immune cells hard at work, including B- and T-cells, macrophages, and dendritic cells. B-cells secrete immunoglobulins such as IgA, that help to control bacterial infections. T-cells secrete interleukins, such as IL-10, which has anti-inflammatory properties. IL-10 has been shown to affect mucus secretions of goblet cells and enterocytes. Macrophages are responsible for removing microbes that have penetrated the intestinal wall without causing any major inflammation or a cytokine storm. Dendritic cells are a major contributor to immune function. Goblet cells deliver antigens to dendritic cells, which elicits an immune response. The properties of mucus can be influenced by not only goblet cells and enterocytes, but also the subepithelial immune cells.
Mucus — the Ultimate Bodyguard
Mucus is essentially the intestine’s ultimate bodyguard — it allows enough exposure of intestinal contents to the epithelial cells for the body to be triggered into the appropriate immune response, and also allows for the immune system to communicate with the goblet cells regarding the quantity and type of mucus to produce. Ideally, mucus is providing a happy home to the flora that aid digestion by creating short-chain fatty acids from ingested macronutrients, and also encouraging the absorption of nutrients from our food.
Unfortunately, several savvy pathogens have figured out a way to use mucus as their weapon — for example, E.coli can reside beneath the inner mucus layer, protecting it from clearance and excretion. These pathogens invade by secreting a protease that can cleave MUC2, effectively breaking through the mucus barrier by cutting its way through the amino acid.
Because of the fleeting properties of this super-substance, our understanding of mucus still leaves much to be desired. At DIG Labs, we are developing proprietary methods to characterize mucus visually, and deploy AI-based tools to define associations between mucus and nutrition. Learn more about this and other discovery projects here.
[i] Paone P, Cani PD, Gut 2020; 69: 2232–2243