Gut bacterium Intestinimonas butyriciproducens improves host metabolic health: evidence from cohort and animal intervention studies

Background: The human gut microbiome strongly influences host metabolism via fermentation of dietary components to metabolites that allow communication with peripheral tissues. Short chain fatty acids are among the most known microbial metabolites that signal to the host. Intestinimonas butyriciproducens is a prevalent commensal bacterium that has a unique capability of converting dietary fructoselysine to butyrate and acetate and has a completed fructoselysine catabolic pathway. Dietary fructoselysine is an abundant Amadori product formed in foods during processing and is part of food products rich in dietary advanced glycation end products which can be potentially toxic. Therefore, understanding the role of this bacterium and fructoselysine metabolism in metabolic health is highly relevant. Results: We accessed associations of I. butyriciproducens with metabolic risk biomarkers via both strain and functional levels using a human cohort characterized by fecal metagenomic analysis. We observed that the level of the bacterial strain as well as fructoselysine fermentation genes were reversely associated with BMI, triglycerides, HbA1c and fasting insulin levels. We also investigated degradation capacity of fructoselysine within the Intestinimonas genus using a culture dependent approach and observed that I. butyriciproducens as a key player in the butyrogenic fructoselysine metabolism in the gut. To explore the function of I. butyriciproducens on host metabolism, we employed the diet-induced obesity mouse model to mimic the human metabolic syndrome. Oral supplementation of I. butyriciproducens counteracted body weight gain, hyperglycemia as well as adiposity. Moreover, within the inguinal white adipose tissue, bacterial administration reduced inflammation and promotes pathways involved in browning and insulin signaling. The observed effects are attributable to the formation of the short-chain fatty acids butyrate and acetate from dietary fructoselysine, as their plasma levels were significantly augmented by the bacterial strain, thereby contributing to systemic effects of the bacterial treatment. Conclusions: I. butyriciproducens ameliorates host metabolism in the context of obesity and may thus be a good candidate for new microbiota-therapeutic approaches to prevent or treat metabolic diseases.