Humans are getting fatter! Globally, obesity rates have tripled over the past four decades to 13%, and more than 2 billion people are now overweight (BMI ≥ 25) and obese (BMI ≥ 30) [1]. Obesity negatively affects overall health and greatly increases the risk of developing metabolic-related diseases such as diabetes.
Losing weight is a common topic, fasting, exercise and drugs, all kinds of weight loss methods emerge in an endless stream, but many men and women who lose weight are still losing battles. If you can’t do it, you should ask yourself. We might as well lower our heads and focus our attention on the deep part of our body—the gut through the “swimming ring” on our stomach.
There are about 1,000 kinds of microorganisms in the human intestine, and the intestinal flora composed of these microorganisms is closely related to the nutrition, metabolism and immunity of the human body. Intestinal dysbiosis is thought to be a key factor in obesity and type 2 diabetes. Studies have found that the composition of the gut microbiota in obese individuals is altered compared to normal-weight individuals, suggesting that some The relationship between gut bacteria and obesity is unusual [2].
Recently, a team led by Professor Jun Kunisawa from the National Institute of Biomedical Innovation, Health and Nutrition in Japan found that the intestinal bacterium Bw (Blautia wexlerae) was associated with obesity and type 2 in a population cohort. Diabetes is negatively correlated. In vitro and in vivo experiments confirmed that Bw bacteria can reduce weight, anti-inflammatory and reduce insulin resistance. Mechanism research found that Bw bacteria remodeled the intestinal environment through metabolites. Relevant research was published in “Nature” sub-journal Nature communications[3].
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The researchers first assessed the relationship between gut microbiota and obesity in a population-based cohort study of 217 adult subjects, combining BMI and diabetes prevalence. or type 2 diabetes. Multiple regression analysis showed a high correlation between gut microbiota and BMI and type 2 diabetes.
Further analysis found that four genera of enterobacteria were altered in the guts of obese people and those with type 2 diabetes compared to healthy people of normal weight. The abundance of Megasphaera was increased, while the abundance of Blautia, Butyricoccus and Faecalibacterium decreased.
Among them, Blautia is a genus of intestinal core bacteria, including Bw bacteria, Bs bacteria and Bg bacteria and other abundant bacteria in the intestinal tract. Previous studies have found that the richer the gut Blautia, the smaller the visceral fat area, which is an obesity marker for metabolic disease risk [4]. Therefore, Blautia has become the focus of research on body weight and diabetes-related gut bacteria.
The researchers recruited an additional 195 participants from different regions as a validation cohort to examine the relationship between Blautia and obesity, confirming the decreased abundance of Blautia in the gut of obese individuals.
The researchers then analyzed the abundance of Enterobacteriaceae of the genus Blautia in the gut and found that Bw bacteria predominated in Blautia, with a relative abundance almost equal to the overall abundance of Blautia. These results suggest that Bw bacteria are weight-related enterobacteria that may be effective in improving obesity and type 2 diabetes.
obesity and type 2 diabetes mellitus (T2DM)-related enterobacteria were screened in a population cohort to obtain Bw bacteria
After screening the Bw bacteria in the human cohort, the researchers then explored in animal models, dividing the mice into a normal diet group, a high-fat diet group, and a high-fat diet simultaneously orally Bw bacteria group.
Compared with the normal group, the high-fat diet mice had increased body weight, visceral fat accumulation, elevated fasting blood glucose and insulin levels, abnormal glucose tolerance test, insulin resistance and visceral fat inflammation, suggesting that High-fat diet induces obesity and type 2 diabetes.
While high-fat feeding and oral administration of Bw bacteria resulted in slower weight gain, lower fat accumulation, normal fasting blood glucose and insulin levels, insulin sensitivity, and decreased intra-adipose inflammatory cells and pro-inflammatory factors in mice . These results suggest that Bw bacteria can ameliorate high-fat diet-induced obesity and diabetes.
The researchers then dissected the mice to explore the metabolic changes after oral administration of Bw bacteria, and found that succinate levels were significantly increased in fat, muscle and liver tissue. Succinate can control body weight by regulating appetite, energy intake and consumption, and lipid oxidation, which is a metabolic marker of energy consumption [5], suggesting that Bw bacteria can reduce body weight by promoting energy consumption in the body.
Obesity can induce adipocytes to produce pro-inflammatory factor S100A8, activate macrophages, and then induce fat inflammation and lead to diabetes [6]. The expression of inflammatory factors in adipocytes decreased after oral administration of Bw bacteria in mice, prompting researchers to study its mechanism. In vitro experiments found that the supernatant of Bw bacteria treated adipocytes, which reduced the expression of S100A8 in adipocytes, suggesting that Bw bacteria reduced the expression of S100A8 in adipocytes through the metabolites produced, thereby inhibiting adipose inflammation and reducing diabetes.
In vivo experiments found that Bw bacteria can reduce obesity and diabetes caused by high-fat diet
In order to determine the effective metabolites of Bw bacteria to control obesity and diabetes, the researchers conducted a pathway analysis of the metabolism of Bw bacteria and found that compared with other core intestinal bacteria, The amino acid metabolism and carbohydrate metabolism of Bw bacteria are unique.
In terms of amino acid metabolism, Bw bacteria produce large amounts of S-adenosylmethionine, acetylcholine and L-ornithine. The researchers treated adipocytes with these three substances separately and found that they reduced the accumulation of triglycerides in a dose-dependent manner. Among them, S-adenosylmethionine also inhibited the expression of S100A8, indicating that these compounds have the ability to modulate lipids. Metabolic and anti-inflammatory effects are effector metabolites of Bw bacteria in controlling obesity and diabetes.
In terms of carbohydrate metabolism, Bw bacteria are rich in amylose and directly produce three short-chain fatty acids, succinic acid, lactic acid and acetic acid, from starch. Short-chain fatty acids can reduce fat accumulation and inflammation through the gut-liver axis, reduce insulin resistance and improve diabetes [7].
However, the researchers noticed that the concentration of two short-chain fatty acids, propionate and butyrate, in the intestines of mice also increased after oral administration of Bw bacteria, while Bw bacteria did not directly produce propionate. acid and butyric acid, suggesting that Bw bacteria promoted the proliferation of propionic and butyric acid-producing Enterobacteriaceae. Intestinal flora analysis showed that probiotics such as Akkermansia, Rikenellaceae RC9 and Butyricoccus increased in abundance after the addition of Bw bacteria, which can use succinic acid, lactic acid or acetic acid as substrates , producing propionic acid and butyric acid. These results suggest that Bw bacteria can improve the intestinal environment and inhibit obesity and diabetes by increasing the short-chain fatty acids and probiotics in the intestine.
Mechanism exploration found that Bw bacteria remodel the intestinal environment through metabolites
In conclusion, this study combined human cohort, animal experiments and cell experiments to screen and identify a novel gut probiotic negatively associated with obesity and type 2 diabetes- ─Bw bacteria. With its unique amino acid and carbohydrate metabolites, Bw bacteria reshape the gut environment for weight loss, anti-inflammatory and insulin resistance, and suppress obesity and type 2 diabetes. These findings reveal unique regulatory pathways of microbial metabolism to the host, which are expected to provide new strategies for the prevention and treatment of metabolic disorders.
Treading through the iron shoes is nowhere to be found, and it takes no effort to get it. With the continuous deepening of human’s understanding of intestinal flora, maybe one day, the important task of losing weight and preventing diabetes will no longer only rely on human beings to “keep their mouths and open their legs”, but will fall on those living in the intestines and The little cuties we accompany day and night.
References:
[1] The Lancet Gastroenterology Hepatology. Obesity: another ongoing pandemic. Lancet Gastroenterol Hepatol. 2021;6(6):411. doi:10.1016/S2468-1253(21)00143-6
[2] Gurung M, Li Z, You H, et al. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine. 2020;51:102590. doi:10.1016/j.ebiom .2019.11.051
[6] Sekimoto R, Fukuda S, Maeda N, et al. Visualized macrophage dynamics and significance of S100A8 in obese fat. Proc Natl Acad Sci U S A. 2015;112(16): E2058-E2066. doi:10.1073/pnas.1409480112
[7] Zhang S, Zhao J, Xie F, et al. Dietary fiber-derived short-chain fatty acids: A potential therapeutic target to alleviate obesity-related nonalcoholic fatty liver disease. Obes Rev. 2021;22(11):e13316. doi:10.1111/obr.13316
Writing | Chen Nencao
Edit | Swagpp