Gut bacterium associated with reduced dietary sugar intake

These findings could lead to the development of effective therapies for the treatment of obesity and metabolic diseases such as type 2 diabetes

In an article in Natural microbiologyresearchers investigated the mechanism behind sugar preference and its link to diabetes, focusing on the role of a free fatty acid receptor and the gut microbiota.

Their findings indicate that reduced expression of this receptor in mouse models and diabetes patients is associated with higher sugar intake.

Background

Animals are biologically programmed to crave sugar, but high sugar consumption can increase blood glucose and increase the risk of developing metabolic diseases. The exact causes of diabetes remain unclear, although factors such as obesity, diet, genetics and aging contribute to its onset. High sugar intake is a significant environmental risk linked to increased rates of cardiovascular disease, type 2 diabetes and obesity.

The rising consumption of sugary foods worldwide has led to a preference for sugary diets, which scientists believe is the cause of overconsumption and the growing diabetes epidemic. Sugar preference occurs when animals associate the taste of sugar with its internal effects. However, the mechanisms behind this behavior are not fully understood due to the complex interactions between the nervous system and the hormonal system.

The gut microbiota, which influences immunity, metabolism and brain function, may play a role in shaping dietary preferences. Studies show that gut bacteria influence food intake and appetite regulation through the gut-brain axis.

Changes in the gut microbiota have been associated with dietary behavior, suggesting potential targets for the treatment of diabetes. Specifically, free fatty acid receptors such as Ffar4, activated by long-chain fatty acids, can link genetic and environmental factors in regulating dietary preferences. Understanding this connection can help manage sugar preferences and diabetes.

About the study

Xinmiao Liang, Yong Chen, Shenglong Zhu and colleagues collected peripheral blood from 60 individuals with type 2 diabetes and 24 healthy controls, all of whom met the American Diabetes Association criteria. The expression of Ffar4 messenger ribonucleic acid (mRNA) was assessed. In addition, fecal samples from 45 diabetic patients and 15 healthy individuals were analyzed to quantify their contents Bacteroides vulgatusan intestinal bacteria. Participants gave informed consent and ethical approvals were secured.

For the animal study, 18 male mice were housed under pathogen-free conditions with environmental controls for humidity and temperature and given access to water and food. Ethical guidelines for animal care were followed.

Mice were anesthetized for surgical procedures including drug infusions and gene silencing in the brain. Microglia were isolated using density gradient centrifugation after digestion and filtration of brain tissue.

Dietary preferences were tested by offering mice diets with a high fat or sugar content in addition to normal diets. Liquid preference was assessed using tests with two bottles of different sugar solutions. Co-housing experiments were conducted to observe behavioral interactions between different mouse strains.

Mice underwent antibiotic treatment followed by fecal microbiota transplantation. Gene sequencing analyzed the composition and diversity of the microbial community. B. vulgatus was grown under anaerobic conditions and metabolomic analysis was performed by assessing bacterial metabolites.

Various cell lines were grown and mice were given treatments such as pantothenate and liraglutide to study their effects on glucose metabolism.

Findings

Researchers found that Ffar4 expression was significantly reduced in diabetic patients and mice. Lower Ffar4 levels were associated with a stronger preference for sugar. When Ffar4 was specifically deleted in the intestines of mice, their sugar preference increased. Conversely, overexpression of Ffar4 in the intestines reduced their sugar cravings.

The study identified a key mechanism involving the gut bacteria B. vulgatus. Ffar4 modulates the abundance of B. vulgatuswhich produces a metabolite called pantothenate. Pantothenate increases the secretion of the hormone glucagon-like peptide-1 (GLP-1), which in turn stimulates the liver to release a hormone that reduces sugar preference. Lower levels of B. vulgatus and pantothenate were observed in diabetic mice, which correlated with increased sugar consumption.

Further experiments confirmed that supplementation B. vulgatus or pantothenate reduced sugar preference in diabetic mice and lowered their fasting blood glucose levels. This suggests that targeting the Ffar4B. vulgatusThe pantothenate pathway could be a potential strategy for controlling sugar cravings and improving glucose control in diabetes.

Conclusions

This study specifically examines the link between the gut microbiota Bacteroides vulgatusand sugar preference, revealing a role for the Ffar4 receptor in this process. Ffar4, best known for its involvement in fatty acid metabolism, also affects sugar cravings.

The research highlights that Ffar4 deficiency reduces B. vulgatus levels, which affect pantothenic acid production. This metabolite increases the secretion of the GLP-1 hormone, which stimulates the liver to release a hormone that regulates sugar intake by sending signals to the brain.

The study confirms that this hormone, called FG21, directly influences sugar preference, independently of the GLP-1 receptors in the brain. The findings suggest that targeting Ffar4 or supplementing with specific probiotics may help prevent diabetes by modulating sugar preference.

Furthermore, the authors pointed out the importance of interactions between gut, liver and brain in feeding behavior. They called for further research into how the brain’s reward systems may be involved in Ffar4-mediated sugar cravings.