Translating gut microbiome research into therapies for type 1 diabetes.

Type 1 diabetes (T1D) is characterised by the loss of functional pancreatic β-cells, for which lifelong insulin therapy remains the standard of care. Given that the gut microbiome can influence host health and that shifts in gut microbial profiles have been observed in T1D, growing interest has emerged in the role of the gut microbiome in T1D, particularly for its therapeutic potential. The current review aims to provide an overview of existing knowledge on the gut microbial metabolic pathways and microbiota-derived metabolites that are dysregulated or altered in T1D. Subsequently, we address recent advances in gut microbiome-based therapies, ranging from prebiotics to faecal microbiota transplantation (FMT) in both preclinical and clinical studies. Observational studies in T1D have demonstrated alterations in short-chain fatty acid, secondary bile acid and tryptophan metabolism, as well as changes in the abundance of certain gut microbes and the expression of microbial genes involved in these metabolic pathways. Moreover, gut microbiome-targeting strategies have been shown to improve certain glycaemic and immunological parameters in T1D as well as the gut microbial community composition. Nonetheless, findings are highly heterogeneous among studies, also depending on the characteristics of the population studied. While microbiome-based interventions hold promise as a novel therapeutic approach for T1D, expanding the repertoire of gut microbiome-based therapies and conducting more robust clinical trials are crucial steps to substantiate current findings and establish their efficacy before these interventions can be applied as adjunctive therapies in T1D.