Probiotic Bw suppresses obesity and diabetes by improving the intestinal environment

Recently, a team led by Professor Jun Kunisawa at the National Institute for Biomedical Innovation, Health and Nutrition in Japan found that the intestinal bacterium Bw (Blautia wexlerae) was negatively associated with obesity and type 2 diabetes in a population-based cohort. In vitro and in vivo experiments confirmed that Bw bacteria can reduce weight, anti-inflammation and insulin resistance, and the mechanism was explored to find that Bw bacteria reshape the intestinal environment through metabolites. The study was published in Nature communications.

Data show that globally, obesity rates have tripled over the past 40 years, with more than 2 billion people now overweight (BMI ≥ 25) and obese (BMI ≥ 30). Obesity has a negative impact on systemic health and greatly increases the risk of developing metabolic-related diseases such as diabetes. While dysbiosis of the gut flora is thought to be a key contributor to obesity and type 2 diabetes, one study found changes in the composition of the gut flora in obese individuals compared to normal weight individuals, suggesting an unusual relationship between certain gut bacteria and obesity.

Researchers first assessed the relationship between gut flora and obesity or type 2 diabetes in a population-based cohort study of 217 adult subjects with a combination of BMI and diabetes prevalence. Multiple regression analysis showed a high correlation between gut flora and BMI and type 2 diabetes. Further analysis revealed that four genera of enteric bacteria were altered in the intestine of obese individuals and type 2 diabetic patients compared to healthy individuals with normal weight. Megasphaera increased in abundance and Blautia, Butyricoccus and Faecalibacterium decreased in abundance. Among them, Blautia is the core genus of intestinal bacteria, including several bacteria abundant in the intestine such as Bw bacteria, Bs bacteria and Bg bacteria. Previous studies have found that the more abundant intestinal Blautia, the smaller the visceral fat area, which is an obesity marker for metabolic disease risk. Therefore, Blautia became the focus of research on weight- and diabetes-related intestinal bacteria.

The researchers recruited an additional 195 participants from different regions as a validation cohort to examine the relationship between Blautia and obesity, and confirmed the decreased abundance of Blautia in the intestine of obese individuals. The researchers then analyzed the abundance of enterobacteria of the genus Blautia in the gut and found that Bw bacteria dominated Blautia with a relative abundance almost equal to the overall abundance of Blautia. These results suggest that Bw bacteria are weight-associated enterobacteria that may be effective in ameliorating obesity and type 2 diabetes. The researchers then explored in a mouse animal model and found that Bw bacteria improved high-fat diet-induced obesity and diabetes.

To determine the effective metabolites of Bw bacteria in controlling obesity and diabetes, the researchers performed pathway analysis of Bw bacteria metabolism and found that Bw bacteria had unique amino acid metabolism and carbohydrate metabolism compared to other core intestinal enterobacteria. In terms of amino acid metabolism, Bw bacteria produce large amounts of S-adenosylmethionine, acetylcholine and L-ornithine. The researchers treated adipocytes with these two substances separately and found that they reduced triglyceride accumulation in a dose-dependent manner, with S-adenosylmethionine also inhibiting the expression of S100A8, suggesting that these compounds have regulatory and anti-inflammatory effects on lipid metabolism. In terms of carbohydrate metabolism, Bw bacteria are intracellularly rich in straight-chain starch and use starch to directly produce three short-chain fatty acids, succinate, lactate and acetate. Short-chain fatty acids reduce fat accumulation and inflammatory responses via the enterohepatic axis, reducing insulin resistance and thus improving diabetes.

However, the researchers noted that the concentration of two short-chain fatty acids, propionic acid and butyric acid, also increased in the intestine of mice after oral administration of Bw bacteria, which did not directly produce propionic acid and butyric acid, suggesting that Bw bacteria promoted the proliferation of propionic acid- and butyric acid-producing enteric bacteria. Analysis of the intestinal flora showed an increase in the abundance of probiotic bacteria such as Akk, Rik and But bacteria, which were able to produce propionic and butyric acids using succinic, lactic or acetic acid as substrates, after the addition of Bw bacteria. These results suggest that Bw bacteria improve the intestinal environment and suppress obesity and diabetes by increasing short-chain fatty acids and probiotics in the intestine.

In summary, this study combined population-based cohorts, animal studies and cellular experiments to screen and identify a new probiotic bacterium negatively associated with obesity and type 2 diabetes, Bw. Bw, with its unique amino acid and carbohydrate metabolites, reshapes the intestinal environment to reduce weight, anti-inflammatory and insulin resistance, and suppress obesity and type 2 diabetes. These findings reveal unique regulatory pathways of microbial metabolism on the host and are expected to provide new strategies for the prevention and treatment of metabolic disorders.