Succinate Explains Why Prebiotic Fiber Improves Blood Sugar Levels

Eating plenty of fiber is associated with multiple health benefits.

This is largely because fiber is resistant to human digestive enzymes and passes undigested down into the colon.

In the colon, gut bacteria ferment the fibers, producing beneficial byproducts such as short-chain fatty acids (SCFAs). Another less-known byproduct is succinate.

A recent study examined the health benefits of succinate in mice fed a high-fiber diet. Below is a summary of its findings, as well as some background information.

Background

This article uses several terms that some readers may be unfamiliar with. Here are simple explanations.

Blood sugar control: Refers to the body’s ability to keep blood sugar levels stable and within healthy limits.

Intestinal gluconeogenesis (IGG): The formation of new glucose (sugar) by intestinal cells. IGG may improve blood sugar control by suppressing glucose production in the liver (1).

G6pc: A gene that is necessary for the production of new glucose in the body. Intestinal gluconeogensis cannot take place without it.

Prebiotic fiber: A type of fiber that promotes the growth of beneficial gut bacteria.

Fructo-oligosaccharides (FOS): A type of prebiotic fiber found in various fruits and vegetables. FOS are also sold as a dietary supplement.

Succinate: An organic acid (dicarboxylic acid) produced by certain gut bacteria when they are exposed to prebiotic fiber.

Prevotella copri: A type of gut bacteria that produces succinate from fiber.

Cecum: The mouse/rat equivalent of the human colon.

Article Reviewed

European researchers investigated the metabolic effects of succinate formation in the intestinal tracts of mice. This is the first study to focus on its health effects.

Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis.

Study Design

This series of interventional studies in mice tested the effects of a high-fiber or succinate-rich diet on blood sugar control.

To examine whether succinate leads to improved blood sugar control by initiating intestinal gluconeogensis (IGG), the researchers included two groups of mice:

  • Normal mice: This group included normal mice with all genes necessary for IGG.
  • G6pc-knockout mice: This group included intestinal-specific G6pc-knockout mice. Since they were lacking the G6pc gene, IGG did not take place.

In both groups, the mice were on a high-fat, high-sucrose diet. The experiment was further divided into two parts, depending on supplementation.

  • Prebiotic fiber: The diet was supplemented with fructo-oligosaccharides, a soluble, prebiotic fiber.
  • Succinate: The diet was supplemented with succinate.

Additionally, the study had two extensions. First, a separate part of the study examined the effects of a high-succinate diet on glucose formation in rat intestines.

Second, the researchers investigated the effects of supplementing with a type of bacteria known as Prevotella copri, which produces succinate.

Bottom Line: This series of interventional studies in mice and rats investigated the effects of succinate on blood sugar control.

Finding 1: A High-Fiber Diet Changed Gut Microbiota

Many previous studies clearly show that a diet high in prebiotic fiber affects gut microbiota — the types and relative abundance of bacteria living in the colon.

Additionally, studies show that a diet high in prebiotic fiber changes the gut microbiota in mice, irrespective of whether they are G6pc-knockout or not (2).

The current study supports earlier studies, showing that eating prebiotic fiber (fructo-oligosaccharides) significantly changed the gut microbiota in mice, regardless of whether they had the G6pc gene or not.

Specifically, prebiotic fiber increased the abundance of bacteria in the Bacteroidetesgroup, which includes Prevotella, relative to the Firmicutes group.

The Bacteroidetes group includes species of bacteria that are the major producers of succinate in the digestive tract (34).

Bottom Line: A diet high in prebiotic fiber significantly increased the abundance of bacteria that produce succinate.

Finding 2: Succinate Levels Increased on a High-Fiber Diet

Recent studies show that the levels of succinate in mouse cecum are elevated after eating fiber, and this increase is even more significant on a high-fat diet (567).

This is consistent with the present study’s findings. The researchers detected a significant increase in cecum succinate after a high-fat, high-sugar diet enriched with prebiotic fiber (fructo-oligosaccharides). This happened in both groups of mice.

Additionally, succinate levels rose higher than those of short-chain fatty acids, such as propionate and butyrate.

However, succinate levels were unchanged in the blood circulation, suggesting that most of it is metabolized in the intestines.

Bottom Line: A diet high in prebiotic fiber significantly increased the levels of succinate in mouse cecum (colon).

Finding 3: Succinate Improved Blood Sugar Control

The researchers discovered that when rats were fed succinate, it was converted into glucose by intestinal cells.

This process is known as intestinal gluconeogenesis (IGG). Some scientists consider IGG to be a key regulator of the body’s energy balance (28).

Contrary to what you might think, studies show that IGG actually improves blood sugar control (19).

The present results are in agreement with previous findings. The study showed that succinate reduced blood sugar and insulin levels by suppressing glucose production in the liver.

However, succinate only improved blood sugar control in the normal mice, whereas the G6pc-knockout mice experienced no benefits.

These findings are consistent with studies showing that mice lacking the G6pc gene, which is necessary for IGG, did not benefit from a diet high in prebiotic fiber (fructo-oligosaccharides) (2).

Taken together, the results suggest that prebiotic fiber and succinate improve blood sugar control through their effects on IGG.

Bottom Line: Supplementing with succinate significantly improved blood sugar control by stimulating intestinal gluconeogenesis.

Finding 4: Prevotella copri Increased Succinate Levels and Improved Blood Sugar Control

Several types of bacteria produce succinate when exposed to dietary fiber.

These include bacteria of the Prevotella group, most notably Prevotella copri, which is found in the human digestive tract (10).

The present study tested the effects of supplementing the diet of mice with a live culture of P. copri.

The researchers found that supplementing with P. copri significantly increased blood sugar control (glucose tolerance), an effect that was linked with a reduction in liver glucose production.

These findings are in agreement with a previous study showing that a high abundance of P. copri was associated with improved blood sugar control in healthy people (11).

Interestingly, P. copri benefited both the normal mice and the G6pc-knockout mice, indicating that P. copri has additional, succinate-independent benefits on blood sugar control.

Bottom Line: Supplementing with Prevotella copri, a type of succinate-producing bacteria, improved blood sugar control, irrespective of intestinal gluconeogenesis.

Limitations

Since this was a series of studies in mice and rats, the findings do not necessarily apply to humans.

Although basic metabolism is similar in rodents and humans, randomized controlled trials are needed to confirm the health effects of succinate in people.

Summary and Real-Life Application

In short, this series of studies in rats and mice suggests the following:

  • Prebiotic fiber (fructo-oligosaccharides) increases the abundance of gut bacteria that produce succinate.
  • A diet high in prebiotic fiber increases succinate levels in the digestive tract.
  • Supplementing with succinate improves blood sugar control.
  • Succinate is converted to glucose by intestinal cells, a process known as intestinal gluconeogenesis (IGG).
  • IGG improves blood sugar control by inhibiting liver gluconeogenesis.
  • Mice that do not have the gene (G6pc) necessary for IGG do not benefit from supplementing with fructo-oligosaccharides or succinate.
  • Supplementing with Prevotella copri, a succinate-producing bacteria, improves blood-sugar control in normal and G6pc-knockout mice, suggesting that it may have succinate-independent benefits.

Succinate may have similar benefits in humans. However, randomized controlled trials in people are needed before any strong conclusions can be reached.

Leave a Reply

Your email address will not be published. Required fields are marked *