NOvel MIcrobiome Therapeutics to limit autoimmunity and improve glycaemic control in type 1 diabetes mellitus ( NOMIT)

Despite continuous advancements in the management of type 1 diabetes (T1D) and development of glucose-monitoring and insulin-administering devices, T1D remains a high-burden disease with high-risk of comorbidities, a negative impact on patients’ quality of life and financial strain to the healthcare system.

Recent evidence indicates that aberrant gut microbiota composition underpins T1D and alters the pool of microbially-derived metabolites, which act as endocrine/signaling molecules in the host.

Recently, we identified  a novel microbial metabolite, 6-bromotryptophan (6-BT), and a commensal bacterium, Desulfovibrio piger, that associate with preserved beta-cell function in human T1D. Moreover, using pre-clinical models, we found that both 6-BT and D. piger protect pancreatic islets from the immune cell infiltration, which results in the autoimmune destruction of insulin-producing beta cells.

With this project we will investigate for the first time the effects of 6-BT and D. piger on beta-cell function and the systemic immune-landscape in human T1D. To this end, we will perform two placebo-controlled trials in which new-onset T1D patients will receive daily enteric capsules containing 6-BT, D. piger cells  or the respective placebo capsules for 4 weeks.

Overall, delaying or reversing T1D progression by simple dietary supplementation of natural metabolite or of probiotics, is expected to have a great impact on society, healthcare costs and patients’ life quality, being a relatively cheap and in-house intervention strategy.