Gut microbes use common nutrient choline to fight type 2 diabetes

Good news! Is a choline dietary supplement a good idea?

"... Earlier this year, for example, it was found that an antibiotic primarily used in veterinary medicine was able to convince the microbes in mouse guts to produce colonic acid, a life-extending compound.

Now, a team led by a researcher ... has figured out another powerful way our gut microbes can help us out – this time by tamping down inflammation caused by a fatty diet, keeping our insulin response in check and, in turn, warding off diabetes. ...

The researchers found that one of the chemicals involved in this cascade of negative effects is the immune-system protein IRAK4, which triggers inflammation in the presence of a high-fat diet as a sort of alarm bell. When that protein is expressed for an extended period of time, it leads to insulin resistance and diabetes. ...

Using mice, human cell models, and molecular target-screening, the scientists found that when the nutrient choline hits the gut, microbes convert it into a metabolite called trimethylamine (TMA). TMA, in turn, binds to IRAK4, blocks its activity, reduces inflammation, and restores insulin sensitivity. ..."

"An international research team ... has uncovered a surprising ally in the fight against insulin resistance and type 2 diabetes: a microbial metabolite called trimethylamine (TMA). ... the study reveals that TMA, produced by gut bacteria from dietary choline can block a key immune pathway and improve blood sugar control. ..."

From the abstract:

"The global type 2 diabetes epidemic is a major health crisis. Although the microbiome has roles in the onset of insulin resistance (IR), low-grade inflammation and diabetes, the microbial compounds controlling these processes remain to be discovered.
Here, we show that the microbial metabolite trimethylamine (TMA) decouples inflammation and IR from diet-induced obesity by inhibiting interleukin-1 receptor-associated kinase 4 (IRAK4), a central kinase in the Toll-like receptor pathway sensing danger signals. TMA blunts TLR4 signalling in primary human hepatocytes and peripheral blood monocytic cells and rescues mouse survival after lipopolysaccharide-induced septic shock.
Genetic deletion and chemical inhibition of IRAK4 result in metabolic and immune improvements in high-fat diets.

Remarkably, our results suggest that TMA—unlike its liver co-metabolite trimethylamine N-oxide, which is associated with cardiovascular disease—improves immune tone and glycemic control in diet-induced obesity. Altogether, this study supports the emerging role of the kinome in the microbial–mammalian chemical crosstalk."

Gut microbes use common nutrient to fight type 2 diabetes

Microbial molecule offers new hope for diabetes (original news release)

Inhibition of IRAK4 by microbial trimethylamine blunts metabolic inflammation and ameliorates glycemic control (open access)

Fig. 1: Choline supplementation improves glucose homoeostasis and inflammation after 5 months of HFD [high fat diet].