Why Mucus-Eating Bacteria Stimulate a Healthy Gut
Finally understanding the Akkermansia muciniphila paradox
A thick mucus layer covering the intestinal lining is critical for health, and mucus-degrading bacteria appear as markers of good intestinal health. How can that be?
The mucus layer is vital to maintaining intestinal health
The double mucus layer in humans is critical to a good intestinal health. This gel-like structure protects the fine intestinal lining against mechanical, chemical and biological attacks, and contributes to the maintenance of homeostasis.
The outer mucus layer is home to many microorganisms that thrive on the sugars that compose mucins. Closer to the intestinal cells, the inner mucus layer is thought to be impenetrable to bacteria, in a healthy state. This function is key to protecting the gut lining and whole body from gut permeability, or leaky gut, and the associated endotoxemia and chronic low-grade inflammation.
The mucus layer also has a housekeeping role : it cleans the gut from debris and bacteria, by collecting such debris and flushing them away with the bowel movements.
Mucus production and mucus cycle
Goblet cells, the cells producing mucins, represent growing proportions from the duodenum to the colon, from 4% in the beginning of the gastrointestinal tract to 16% near the end. These cells produce and assemble monomers into dimers, trimers, hexamers, and thanks to the geometrical structure taking place, mucins swell and multiply in volume by 100 to 1000 times, covering the surface of the epithelium by a 200 micrometers thick coating. This translates to a production of about 10 L per day of mucus in a human gut!
We don’t excrete 10 L a day, so where do the mucins end?
In a system in balance, the mucus produced each day is degraded by mucin-eating bacteria, such as Akkermansia muciniphila, B. bifidum, B. thetaiotaomicron, B. fragilis, etc. Degraded into what? Into short chain fatty acids (SCFA), leading to the production, directly or indirectly, of butyrate, which serves a fuel for the goblet cells to produce new mucins.
With this simple cycle in mind, it’s easy to understand why mucus-degrading bacteria stimulate the de novo production of mucus: they feed the goblet cells with the much-needed butyrate enabling the virtuous cycle to go on.
When there are not enough mucin-degraders, there is not enough butyrate, thus not enough mucin produced, thus bad conditions for mucin degraders, and this is the beginning of a vicious cycle that can lead to dysbiosis and leaky gut.
What is the role of fiber in this?
Diets rich in protein and low in fiber stimulate the growth of Proteobacteria to the detriment of Firmicutes and of mucus thickness (Li et al., 2015). The lack of fiber in the diet leads to an aggressive mucobiota: there is an overgrowth of mucus-degrading bacteria because the fiber-degrading bacteria can’t compete. The excess mucolysis destablizes the capacity of goblet cells to regenerate mucus, thus the inner mucus layer becomes smaller and smaller, increasing the contact of pathogens with enterocytes.
So, in a fiber depleted colon, mucin degraders proliferate. As long as they produce SCFA, you should be fine, right? Not really. First, they may produce SCFA but not butyrate, and if there are not enough cross-feeders ending the work, that won’t do the trick to feed the goblet cells and regenerate mucus. Second, fiber-eating bacteria also produce short-chain fatty acids including butyrate, so altogether less fiber tends to mean less butyrate, translating into a high risk of erosion and barrier dysfunction.
Crucially, this analysis from the point of view of mucus balance reminds us that we need mucus-degrading bacteria to prevent mucus overgrowth given the huge amounts of mucus produced every day, and we very much need fiber and fiber-degrading bacteria to prevent mucus thinning and leaky gut. It’s all a matter of balance and biodiversity.
Can a microbiota analysis reveal the state of your intestinal mucus?
Bacteria typical of the outer mucus layer include:
- B. longum subsp. infantis, B. bifidum, B. breve
- R. gnavus, R. torques
- Ruminococcae, Eubacterium subspecies
- Bacteroides thetaiotaomicron, B. vulgatus, B. fragilis
- Akkermansia muciniphila
Although we desire a thick outer mucus, and bacteria associated to mucus are thought to promote mucus secretion, not all these species are markers of a healthy mucobiota. R. torques and gnavus are associated with inflammatory bowel diseases (IBD) and auto-immune diseases and are considered as pathobionts when superating concentrations of 0,1–1%.
Akkermansia muciniphila degrades mucin into mainly propionic and acetic acid so its capacity to stimulate butyrate production depends on cross-feeding with other species to convert these short-chain fatty acids into the precious butyrate. Akkermansia is considered as a marker and actor of good metabolic health, a gatekeeper of the mucosa and could be protective against IBD.
However, its presence is also typical of a diet lacking fiber (anorexia, low food intake, Western diet poor in fiber, diarrhea, with a transit too fast for fiber to stay long enough in the colon, and even constipation, with a transit so slow that fiber is exhausted by bacterial degradation before arriving in the colon) according to Dr. Francesco Di Pierro. In mice for example, increasing fat in the diet reduces fiber intake and stimulates Akkermansia’s growth.
B. thetaiotaomicron, considered a commensal eubiotic species, develops well when the pH is neutral, and incurs stability to the system because it has the ability to shift metabolism from polysaccharide to glucose (including the olisaccharides in mucins). B. thetaiotaomicron can be considered as the mucus keeper, and antibiotic treatments affecting it, like Metronidazole, can compromise the capacity to regenerate the mucus layer.
Bacteria of the inner mucus layer (meant to be almost impenetrable) include:
- Escherichia subspecies
High levels of these families could be markers of a thin mucous layer, a high risk of leaky gut and chronic low-grade inflammation, and a lack of fiber in the diet.
A healthy mucus layer requires a good balance between mucus production and mucus degradation, which relies on sufficient intakes of dietary fibers to ensure the right balance of bacterial fiber degradation and bacterial mucus degradation and the bacterial diversity that enables the smooth conversion of propionate and acetate into butyrate.
The conclusion is always the same: eat real food, not too much, mostly plants.
“Eat food. Not too much. Mostly plants.” — Michael Pollan.
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