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"Nature" sub-issue: weight loss is expected to "eat" out

Posting time:2023-01-31 13:55:41

"Nature" sub-issue: weight loss is expected to "eat" out

Article source: Chen Nencao, Mays Medical

"Nature" sub-issue: weight loss is expected to "eat"! Japanese scientists found that oral Bw bacteria can improve obesity and type 2 diabetes through metabolic remodeling of intestinal flora

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. Weight loss is a common topic, fasting, exercise and drugs, various 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 considered a key factor contributing to obesity and type 2 diabetes. Studies have found that the composition of intestinal flora in obese people is changed compared with normal weight people, suggesting the relationship between certain intestinal bacteria and obesity. unusual [2]. Recently, a team led by Professor Jun Kunizawa of the National Institute of Biomedical Innovation, Health and Nutrition in Japan found that the intestinal bacteria Bw (Blautia wexlerae) was negatively correlated with obesity and type 2 diabetes in a population cohort. In vitro and in vivo experiments confirmed that Bw Bacteria can lose weight, anti-inflammatory and reduce insulin resistance, and the mechanism study found that Bw bacteria remodel the intestinal environment through metabolites. Relevant research was published in Nature communications, a sub-journal of Nature [3]. Screenshot of the paper The researchers first conducted a population cohort study on 217 adult subjects to detect gut microbiota, and combined BMI and diabetes prevalence to assess the relationship between gut microbiota and obesity or type 2 diabetes. Multiple regression analysis showed a high correlation between gut microbiota and BMI and type 2 diabetes. Further analysis found that compared with healthy people of normal weight, obese people and patients with type 2 diabetes had changes in four genera of enterobacteria in the gut. 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]. As a result, 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 that the abundance of Blautia in the intestines of obese individuals is reduced. The researchers then analyzed the abundance of Blautia enterobacteria 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-related enterobacteria that may be effective in improving obesity and type 2 diabetes. Screening of obesity and type 2 diabetes (T2DM)-related enterobacteria in the population cohort to obtain Bw bacteria After screening for Bw bacteria in the population cohort, the researchers then explored in animal models, dividing the mice into a normal diet group, a high-fat group The diet group and the high-fat diet group were given oral administration of Bw bacteria at the same time. Compared with the normal group, high-fat diet mice gained weight, accumulated visceral fat, increased 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. In contrast, high-fat-fed and oral administration of Bw bacteria resulted in slower weight gain, lower fat accumulation, normal fasting blood glucose and insulin levels, insulin sensitivity, and reduced intra-adipose inflammatory cells and pro-inflammatory factors. These results suggest that Bw bacteria can ameliorate high-fat diet-induced obesity and diabetes. Next, the researchers 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, and is a metabolic marker of energy consumption [5], which suggests 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 to reduce 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 pathway analysis on the metabolism of Bw bacteria and found that compared with other intestinal core intestinal The amino acid metabolism and carbohydrate metabolism of Bw bacteria are unique. In terms of amino acid metabolism, Bw bacteria produced 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 regulate lipid metabolism and resist. Inflammation is an effector metabolite 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 concentrations of two short-chain fatty acids, propionic acid and butyric acid, in the intestines of mice also increased after oral administration of Bw bacteria, while Bw bacteria could not directly produce propionic acid and butyric acid, suggesting that Bw bacteria promote 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. Mechanistic exploration found that Bw bacteria remodel the intestinal environment through metabolites. In conclusion, this study combined population cohort, animal experiments and cell experiments to screen and identify a new intestinal negatively related obesity and type 2 diabetes mellitus. Probiotics - 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. Stepping through the iron shoes, there is nowhere to find it, 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[3] Hosomi K, Saito M, Park J, et al. al. Oral administration of Blautia wexlerae ameliorates obesity and type 2 diabetes via metabolic remodeling of the gut microbiota. Nat Commun. 2022;13(1):4477. Published 2022 Aug 18. doi:10.1038/s41467-022-32015-7[ 4] Ozato N, Saito S, Yamaguchi T, et al. Blautia genus associated with visceral fat accumulation in adults 20-76 years of age. NPJ Biofilms Microbiomes. 2019;5(1):28. Published 2019 Oct 4. doi: 10.1038/s41522-019-0101-x[5] Canfora EE, Meex RCR, Venema K, Blaak EE. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol. 2019;15(5):261-273. doi :10.1038/s41574-019-0156-z[6] Sekimoto R, Fukuda S, Maeda N, et al. Visual ized 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

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