Deciphering benefits of microbial fermentation via the gut brain axis

Filipe De Vadder is a molecular biologist in Gilles Mithieux group and published recently an important article in Cell journal which illustrate how gut microbiota fermentation product could impact neural communication. He accepted for GMFH to give us some highlights.

d888b79662ad606eb1a2440c8e5bd921-624x375

The enzyme responsible for the final reaction in intestinal glucose production is highlighted by immunofluorescence (red) using confocal microscopy. Image: © Inserm / MITHIEUX G. & BESNARD P

1) What is the context of this study?

Dietary fiber has long been known for its beneficial effects on health, including insulin sensitivity. However, no study had provided a clear mechanism explaining the beneficial metabolic effects of dietary fiber. Given the fact that the effects of dietary fiber are quite similar to those of intestinal gluconeogenesis (which we first described in our lab in the beginning of the 2000s decade), we hypothesized that this unique metabolic feature could be the key linking dietary fiber and beneficial metabolic effects. Furthermore, when dietary fiber is metabolized by the gut microbiota, it produces short-chain fatty acids such as propionate, which is classically described as a liver gluconeogenic precursor. This is in contradiction with the benefits of propionate on glucose homeostasis, so we thought that, before reaching the liver, propionate could act as a glucose precursor in the gut.

2) What was the most challenging part of this study?

The precise quantification of intestinal glucose fluxes is always quite challenging because it involves surgery, radioactive measurements and you have to be very careful to sample blood. I also think that sequencing and analyzing the gut microbiota was quite a long and difficult step.

3) What were the main findings?

In this study, we find that propionate initiates a portal-brain neural communication. Furthermore, butyrate and propionate both induce intestinal glucose production, but through different complementary mechanisms. Using mice that are unable to produce glucose specifically in the intestine, we showed that intestinal gluconeogenesis provides a causal link for benefits of dietary fiber.

4) What are limitations?

This is a study on rodents, so of course they are a model that has some limits.

Filipe De Vadder.

Filipe De Vadder.

5) How your study could help clinicians in the future?

Intestinal gluconeogenesis has actually been described in humans so the mechanisms that take place in rodents are very likely to take place in humans too. I think this study could help clinicians to treat obese and diabetic patients with a dietary supplement in fiber. But probably the most important message would be to say that we can prevent this diseases by increasing our intake of dietary fiber.

GMFH Editing Team
GMFH Editing Team