Scientists uncover how gut bacteria’s sugar-derived compounds influence metabolism, helping control blood sugar, reduce fat accumulation, and pave the way for new probiotic therapies.
Study: Sucrose-preferring gut microbes prevent host obesity by producing exopolysaccharides. Image Credit: Kateryna Kon / Shutterstock
In a recent study published in the journal Nature Communications, researchers investigated the role of gut microbiota-derived exopolysaccharides (EPS) in metabolic regulation and host physiology.
Background
Could the bacteria in your gut influence your blood sugar levels alongside your diet? With metabolic disorders like obesity and diabetes reaching epidemic proportions, scientists are exploring new biological mechanisms that regulate metabolism beyond just diet and exercise.
The human gut microbiota is a vital regulator of health, influencing metabolism, immunity, and disease prevention. It houses trillions of bacteria that process dietary components and generate bioactive molecules. Among these, EPS produced by specific gut bacteria, including Streptococcus salivarius, are emerging as key players in metabolic health.
These polysaccharides modulate immune responses, enhance gut barrier function, and interact with host metabolic pathways. With obesity and diabetes on the rise, understanding the gut microbiome’s role is crucial. Although studies suggest microbial EPS impact metabolism, their precise mechanisms remain unclear. Further research is needed to establish how bacterial EPS, particularly from S. salivarius, influences host metabolic regulation.
About the study
Fecal samples from 472 human donors were collected following ethical guidelines. The study did not specify an age range, and individuals with recent antibiotic use, probiotic intake, or metabolic disorders were excluded. Samples were stored at -80°C before processing. Bacteria capable of producing EPS were isolated using anaerobic culture techniques and identified using shotgun metagenomic sequencing and 16S ribosomal ribonucleic acid (rRNA) sequencing.
Mouse experiments were conducted using C57BL/6J and germ-free mice housed under controlled conditions. Mice were assigned to standard or high-fat diets, with or without EPS supplementation. Glucose tolerance tests and insulin sensitivity assays were conducted to assess metabolic effects. Blood samples were collected to measure glucose, insulin, and gut hormone levels.
To investigate microbiome alterations, both metagenomic sequencing and 16S rRNA sequencing were performed to analyze gut microbiota composition. Short-chain fatty acid (SCFA) concentrations were measured using gas chromatography. Cytokine assays were conducted to determine systemic inflammation levels. Metabolic cage studies were performed to assess energy expenditure, food intake, and physical activity.
Statistical analyses included the Student’s t-test for parametric data and the Mann-Whitney U test for non-parametric data. Correlation analyses were performed between bacterial abundance, SCFA levels, and metabolic markers. A p-value < 0.05 was considered statistically significant.
Study results
A strain of Streptococcus salivarius (S. salivarius) was identified as the dominant EPS producer in human gut microbiota. This strain influenced host metabolism by modulating gut hormone levels and SCFAs. In human subjects, individuals with a higher abundance of S. salivarius had lower blood glucose levels and improved insulin sensitivity. However, these findings were correlational, meaning they do not prove that S. salivarius directly causes metabolic improvements in humans.
In mouse models, EPS administration significantly enhanced glucose tolerance and insulin sensitivity. Germ-free mice colonized with S. salivarius exhibited higher glucagon-like peptide-1 (GLP-1) levels, promoting glucose homeostasis. Mice supplemented with EPS also showed reduced body weight and fat mass compared to controls. Long-term monitoring of EPS-fed mice demonstrated sustained improvements in metabolic markers. Insulin sensitivity remained higher, and body weight gain was controlled over 16 weeks.
Metagenomic sequencing revealed that EPS altered gut microbiota composition, increasing the abundance of SCFA-producing bacteria such as Bacteroides and members of the Bacteroidales S24-7 group. SCFA analysis confirmed an increase in acetate and propionate levels, supporting enhanced microbial fermentation activity. Additionally, inflammatory markers were significantly reduced in EPS-treated mice, indicating a protective effect against metabolic inflammation.
Further analysis revealed that mice treated with EPS exhibited reduced markers of inflammation, as measured by lower circulating levels of pro-inflammatory cytokines. This suggests that gut-derived EPS may play a protective role against metabolic inflammation, a key factor in obesity and insulin resistance.
Correlation analysis between human gut microbiota composition and metabolic markers further confirmed that individuals with a higher relative abundance of S. salivarius had improved glucose regulation and lower body mass index (BMI). The presence of these bacteria was significantly associated with increased levels of SCFAs, further supporting the role of EPS in metabolic modulation. However, variations in S. salivarius strains and dietary influences may affect EPS production, meaning the metabolic benefits observed in mice may not fully translate to humans.
To further validate these findings, metabolomic profiling was conducted to assess changes in host metabolic pathways. EPS-treated mice exhibited significant increases in metabolites associated with improved energy metabolism, including enhanced mitochondrial function and fatty acid oxidation.
These findings suggest that EPS not only modulates the gut microbiota but also has a direct impact on host energy metabolism. Notably, the observed effects were dependent on SCFA production by gut microbes rather than EPS acting alone. The observed effects persisted even after dietary intervention ceased, indicating the potential long-term benefits of EPS supplementation.
Additionally, food intake and energy expenditure were evaluated. Mice receiving EPS exhibited lower food intake despite having similar energy expenditure compared to controls. This suggests that EPS may influence satiety signals, potentially through gut hormone modulation. GLP-1 and peptide YY levels were significantly elevated in EPS-treated mice, further supporting this hypothesis.
Conclusions
To summarize, this study highlights the role of gut microbiota-derived EPS in regulating metabolism. S. salivarius, a dominant EPS-producing bacterium in the gut, was associated with improved metabolic markers in humans and enhanced glucose metabolism in mice.
EPS supplementation led to lower blood glucose levels, enhanced insulin sensitivity, and reduced inflammation in both human and mouse models. However, while these findings suggest potential metabolic benefits, further studies are needed to determine the specific mechanisms, strain variations, and long-term effects of S. salivarius in humans.
These findings suggest that microbiota-targeted interventions, such as probiotics or prebiotics, may provide therapeutic benefits for metabolic disorders. Given the global rise in obesity and diabetes, these results raise important questions: Could future probiotic therapies help prevent metabolic disorders? Might gut-derived EPS hold the key to long-term metabolic health?
