Researchers led by Hiroshi Ohno at the RIKEN Center for Integrative Medical Sciences (IMS) in Japan have discovered a type of gut bacteria that could help improve insulin resistance and therefore protect against the development of obesity and diabetes. type 2. The study, published August 30 in the scientific journal Nature, involved a genetic and metabolic analysis of human fecal microbiomes and then corroborated experiments in obese mice.
Summary Insulin resistance is the main pathophysiology underlying metabolic syndrome and type 2 diabetes. Previous metagenomic studies have described the characteristics of the intestinal microbiota and its role in the metabolization of the main nutrients in insulin resistance. In particular, it has been proposed that carbohydrate metabolism of commensals contributes up to 10% of the host’s total energy extraction thus playing a role in the pathogenesis of obesity and prediabetes. However, the underlying mechanism remains unclear. Here we investigate this relationship using a comprehensive multi-omics strategy in humans. We combined fecal metabolomics with metagenomics, host metabolomics, and transcriptomics data to profile the involvement of the microbiome in insulin resistance. These data reveal that fecal carbohydrates, particularly host-accessible monosaccharides, are increased in individuals with insulin resistance and are associated with microbial carbohydrate metabolism and host inflammatory cytokines. We identify gut bacteria associated with insulin resistance and insulin sensitivity that display a distinct pattern of carbohydrate metabolism and demonstrate that bacteria associated with insulin sensitivity enhance host insulin resistance phenotypes in a mouse model. Our study, which provides a comprehensive view of host-microorganism relationships in insulin resistance, reveals the impact of carbohydrate metabolism on the microbiota, suggesting a potential therapeutic target to improve insulin resistance. |
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Insulin is a hormone released by the pancreas in response to blood sugar. Normally, it helps glucose reach the muscles and liver so they can use energy. When someone develops insulin resistance , it means that insulin cannot do its job and as a result, more sugar remains in the blood and the pancreas continues to produce more insulin. Insulin resistance can lead to obesity, prediabetes, and full-blown type 2 diabetes.
Our intestines contain trillions of bacteria, many of which break down the carbohydrates we eat when they would otherwise not be digested. While many have proposed that this phenomenon is related to obesity and prediabetes, the facts are still unclear because there are many different bacteria and metabolic data are lacking. Ohno and his team at RIKEN IMS addressed this gap with their comprehensive study and, in the process, discovered a type of bacteria that could help reduce insulin resistance .
First, they examined as many metabolites as they could detect in the feces provided by more than 300 adults at their regular medical check-ups. They compared this metabolome with insulin resistance levels obtained from the same people. "We found that increased insulin resistance was associated with excess carbohydrates in fecal matter," says Ohno, "especially monosaccharides such as glucose, fructose, galactose and mannose."
Next, they characterized the gut microbiota of the study participants and its relationship to insulin resistance and fecal carbohydrates. The intestines of people with greater insulin resistance contained more bacteria from the taxonomic order Lachnospiraceae than from other orders. Furthermore, microbiomes that included Lachnospiraceae were associated with excess fecal carbohydrates. Thus, an intestinal microbiota dominated by Lachnospiraceae was related to both insulin resistance and stools with excess monosaccharides. At the same time, insulin resistance and monosaccharide levels were lower in participants whose intestines contained more Bacteroidales -type bacteria than other types.
The team then set out to observe the bacteria’s direct effect on metabolism in cultures and then in mice . In culture, Bacteroidales bacteria consumed the same types of monosaccharides found in the feces of people with high insulin resistance, with the species Alistipes indistinctus consuming the greatest variety. In obese mice, the team looked at how treatment with different bacteria affected blood sugar levels. They found that A. indistinctus lowered blood sugar and reduced insulin resistance and the amount of carbohydrates available to the mice.
These results were consistent with findings from human patients and have implications for diagnosis and treatment. As Ohno explains, “due to its association with insulin resistance, the presence of the intestinal bacteria Lachnospiraceae could be a good biomarker of prediabetes . ” Likewise, treatment with probiotics containing A. indistinctus could improve glucose intolerance in people with prediabetes.”
Although most over-the-counter probiotics currently do not contain the bacteria identified in this study, Ohno recommends caution if they are available. "These findings need to be verified in human clinical trials before we can recommend any probiotics as a treatment for insulin resistance."
