The bacterium Akkermansia muciniphila is creating quite a stir in science news, with people calling it the “weight loss bacterium”. While it’s exciting to think about a bacterium that has the ability to reduce body weight with no change in food intake, there’s another reason to get excited: The potential to treat obesity-related metabolic disorders such as type-2 diabetes and perhaps even diseases related to intestinal inflammation.
There are hundreds of bacterial species that colonize the gut. Why has this bacterium been dubbed the “weight loss bacterium”, and why do researchers have such lofty goals for this simple unicellular organism?
The fervor stems from an article in the Proceedings of the National Academy of Sciences that shows A. muciniphila levels in the gut are inversely correlated with body weight in mice—higher levels of this bacterial species are associated with lower body weight—and that higher levels of A. muciniphila reversed fat mass gain, insulin resistance, adipose tissue inflammation and metabolic endotoxemia (i.e., increased plasma bacterial lipopolysaccharide) associated with a high-fat diet (1).
We already know that bacteria in the gastrointestinal tract provide their host with many advantages, including metabolism of carbohydrates that cannot be utilized by the host, increased absorption of nutrients and synthesis of vitamins B and K. The host regulates this symbiotic relationship by maintaining a mucus layer as a gut barrier and secreting antimicrobial peptides and immune system effectors such as IgA into the intestinal lumen. Another tactic is the endocannabinoid system, which deploys peptides such as glucagon-like peptide-1 to maintain glucose homeostasis and lipids such as 2-arachidonoylglycerol to reduce metabolic endotoxemia and inflammation. This relationship and the normal composition of gut microflora are disrupted in individuals fed a high-fat diet or suffering from obesity or type-2 diabetes.
In this study, researchers tested their hypothesis that A. muciniphila plays a critical role in maintaining the gut barrier between host and microbiota and that modulating A. muciniphila levels in the gut can affect physiological and homeostatic functions in the host. The authors first step was to show that A. muciniphila levels were 3300-fold lower in obese and type-2 diabetic mice and 100-fold lower in mice fed a high-fat diet. When a specific prebiotic was introduced in their diet, A. muciniphila levels were restored to normal and the thinning of the inner mucus layer of the gut barrier associated with a high-fat diet was reversed. In addition, body weight, fat mass and fat mass-to-lean mass ratio decreased without a change in food intake. Finally, the health of the mice improved: metabolic endotoxemia was eliminated, diet-induced fasting hyperglycemia was reversed, insulin resistance was reduced and levels of endocannabinoid effectors that reduce inflammation and improve glucose homeostasis were increased. In additional experiments, only mice that were fed viable A. muciniphila exhibited these positive effects; mice fed heat-killed A. muciniphila showed no improvements.
This new research gives scientists new ideas to treat obesity and obesity-related disorders, but the authors caution readers that this is preliminary work. If treatments based on these observations do come to fruition, they are likely to require years of additional research first. So much for my dream of a quick and easy way to shed that extra 20 pounds.
Now if you’ll excuse me, I’m going to go spend some time on the treadmill.
- Everard, A. et al. (2013) Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl. Acad. Sci. USA. PMID: 23671105
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