A multi-omics approach for revealing the crosstalk between the carbohydrate metabolism by gut microbiota and the insulin resistance

Takeuchi T, Kubota T, Nakanishi Y, et al. Gut microbial carbohydrate metabolism contributes to insulin resistance. Nature 2023;6217978:389–95. doi: 10.1038/s41586-023-06466-x.

Carbohydrate metabolism by the gut microbiota has been proposed to contribute to the pathogenesis of obesity and pre-diabetes, but the mechanistic linkage remains unexplained in humans. Takeuchi et al, employed a multi-omics approach, combined the faecal metabolome, the gut microbiome and the host pathology of insulin-resistant (IR) participants to identify the pathogenic gut microbial metabolites compared with individuals with normal insulin sensitivity (IS). The faecal carbohydrates, particularly monosaccharides, accounted for the most of IR-associated co-abundance groups. The analysis on the gut microbial composition at the genus level has clustered participants into four groups. A significantly lower proportion of IR individuals was identified in participants having a Bacteroidales-dominated gut microbiome. Further correlation analysis showed that both Bacteroidales, particularly Alistipes, and KEGG (Kyoto Encyclopaedia of Genes and Genomes) pathways in carbohydrate catabolism were negatively correlated with the IR-associated faecal carbohydrates. In silico analysis showed a mediator role of cytokines in the causal relationship between faecal carbohydrates and IR. The identified IR-associated and IS-associated bacteria were cultured for further investigation on their functional roles. While Bacteroidales distinctively produced metabolites that contribute to the separation of the IR and IS groups, they also preferentially consumed the IR-associated faecal carbohydrates. Alistipes indistinctus was among the most potent species in consuming the IR-associated faecal carbohydrates. The administration of A. indistinctus to mice fed with a high-fat diet most effectively reduced the postprandial blood glucose levels, the carbohydrate oxidation and the serum and faecal IR-associated carbohydrates, suggesting a therapeutic role of A. indistinctus on diet-induced obesity and IR by affecting the intestinal carbohydrate metabolites.

Kupffer cell-like syncytia prevent bacterial dissemination in chronic liver Disease

Peiseler M, Araujo David B, Zindel J, et al. Kupffer cell–like syncytia replenish resident macrophage function in the …