Groundbreaking study uncovers sugar’s effects on the gut and weight gain

[June 5, 2023: Staff Writer, The Brighter Side of News]

A new study published in the journal Cell has revealed that dietary sugar can alter the gut microbiome, leading to a chain of events that results in metabolic disease, pre-diabetes, and weight gain. The findings suggest that while diet plays a significant role in our health, an optimal microbiome is equally important for the prevention of metabolic syndrome, diabetes, and obesity.

The Western-style high-fat, high-sugar diet has been linked to obesity, metabolic syndrome, and diabetes, but it remains unclear how this type of diet triggers unhealthy changes in the body. To investigate this further, researchers led by Ivaylo Ivanov, PhD, associate professor of microbiology & immunology at Columbia University Vagelos College of Physicians and Surgeons, looked into the initial effects of this diet on the gut microbiome of mice.

After four weeks on the diet, the mice exhibited characteristics of metabolic syndrome, including weight gain, insulin resistance, and glucose intolerance. Their microbiomes had also undergone significant changes, with the number of segmented filamentous bacteria – which are common in the gut microbiota of rodents, fish, and chickens – falling sharply and other bacteria increasing in abundance.

The researchers found that the reduction in filamentous bacteria was critical to the animals’ health through its effect on Th17 immune cells.

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The drop in filamentous bacteria led to a decrease in the number of Th17 cells in the gut, which further experiments revealed are necessary to prevent metabolic disease, diabetes, and weight gain. These immune cells produce molecules that slow down the absorption of "bad" lipids from the intestines and decrease intestinal inflammation, thereby keeping the gut healthy and protecting the body from absorbing pathogenic lipids.

The researchers discovered that sugar was responsible for these changes rather than fat. Sugar eliminates the filamentous bacteria, which in turn leads to the disappearance of the protective Th17 cells. When the researchers fed mice a sugar-free, high-fat diet, the mice retained the intestinal Th17 cells and were completely protected from developing obesity and pre-diabetes, even though they consumed the same number of calories.

However, eliminating sugar did not help all the mice. Among those lacking any filamentous bacteria to begin with, the elimination of sugar did not have a beneficial effect, and the animals became obese and developed diabetes. The researchers concluded that some popular dietary interventions, such as minimizing sugars, may only work in people who have certain bacterial populations within their microbiota.

In such cases, certain probiotics might be helpful. In the mice, supplements of filamentous bacteria led to the recovery of Th17 cells and protection against metabolic syndrome, despite the animals' consumption of a high-fat diet. Although humans do not have the same filamentous bacteria as mice, Ivanov believes that other bacteria in humans may have the same protective effects.

Providing Th17 cells to the mice also provided protection and may also be therapeutic for people. "Microbiota are important, but the real protection comes from the Th17 cells induced by the bacteria," Ivanov said.

"Our study emphasizes that a complex interaction between diet, microbiota, and the immune system plays a key role in the development of obesity, metabolic syndrome, type 2 diabetes, and other conditions," Ivanov said. "It suggests that for optimal health, it is important not only to modify your diet but also improve your microbiome or intestinal immune system, for example, by increasing Th17 cell-inducing bacteria."

This study highlights the importance of the gut microbiome and how it can affect our overall health. It also underscores the need for further research into the interactions between diet, microbiota, and the immune system, particularly in the prevention and treatment of metabolic diseases like obesity, pre-diabetes, and type 2 diabetes.

Metabolic diseases have become a global epidemic, affecting millions of people worldwide. According to the World Health Organization (WHO), the number of adults with diabetes has quadrupled since 1980, reaching 422 million in 2014. Moreover, the prevalence of obesity has nearly tripled since 1975, with more than 1.9 billion adults being overweight, of whom over 650 million are obese.

Despite the significant burden of these diseases, their causes remain poorly understood, and current treatments are often ineffective, highlighting the need for novel therapeutic approaches. One promising avenue is the modulation of the gut microbiome, which has been linked to a wide range of health outcomes, including obesity, diabetes, inflammatory bowel disease, and even mental health disorders.

The gut microbiome refers to the trillions of microorganisms that inhabit the human digestive tract, including bacteria, viruses, fungi, and other microbes. These organisms play a crucial role in digestion, nutrient absorption, and immune function, and their composition can vary widely between individuals, depending on factors such as diet, age, genetics, and environment.

Recent studies have suggested that changes in the gut microbiome may contribute to the development of metabolic diseases by altering the production and absorption of key hormones and metabolites, such as insulin, glucagon-like peptide 1 (GLP-1), and short-chain fatty acids (SCFAs).

For example, studies have shown that obese individuals have a less diverse gut microbiome than lean individuals, with a higher proportion of pro-inflammatory bacteria and a lower proportion of beneficial bacteria, such as Bifidobacterium and Lactobacillus.

Moreover, experimental studies in mice have demonstrated that transplanting fecal microbiota from obese animals to lean animals can induce weight gain and metabolic dysfunction, highlighting the potential role of the microbiome in disease development.

Given the growing evidence linking the gut microbiome to metabolic health, researchers are now exploring ways to manipulate the microbiome for therapeutic purposes. One approach is to use probiotics, which are live microorganisms that can confer health benefits when consumed in sufficient quantities.

Numerous probiotic strains have been shown to improve metabolic parameters in animal models, including reducing body weight, improving glucose tolerance, and enhancing insulin sensitivity. However, the effectiveness of probiotics in humans remains uncertain, as the results of clinical trials have been mixed.

Another approach is to use prebiotics, which are dietary fibers that selectively promote the growth of beneficial gut bacteria, such as Bifidobacterium and Lactobacillus. Prebiotics have been shown to improve metabolic health in both animal models and humans, with studies demonstrating reductions in body weight, waist circumference, and blood glucose levels.

Finally, fecal microbiota transplantation (FMT) is an emerging therapy that involves transplanting fecal matter from a healthy donor to a patient with a diseased microbiome. FMT has been used successfully to treat a range of gastrointestinal disorders, such as Clostridium difficile infection and inflammatory bowel disease, and is now being investigated as a potential therapy for metabolic diseases.

The findings suggest that diet matters, but an optimal microbiome is equally important for the prevention of metabolic syndrome, diabetes, and obesity. Further research is needed to understand the complex interactions between diet, microbiota, and the immune system and to develop effective therapies for metabolic diseases.

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