ESPE Yearbook of Paediatric Endocrinology

Brief summary: Using in-depth multi-omics analyses of human type 1 diabetes (T1D) samples, the authors profiled gut microbial functional and metabolic alterations. The T1D microbiota showed decreased butyrate production and bile acid metabolism and increased lipopolysaccharide (LPS) biosynthesis. Fecal microbiota transplantation in animal models proved that T1D gut microflora is a causative factor in the regulation of glucose metabolism.

The etiology of T1D is known to be multifactorial, consisting of genetic susceptibility and environmental factors (1). Among the environmental factors, there is an increasing interest in the role of gut microbiota alterations. Intestinal commensal bacteria play a crucial role in host physiology in health and disease by regulating endocrine and immune functions. An aberrant gut microbiome structure and function have been documented prior and during T1D onset (2), but an extensive profiling of functional and metabolic abnormalities of gut microbiota in T1D is lacking.

This study reveals a unique T1D-associated gut dysbiosis, characterized by increased LPS biosynthesis and decreased butyrate production and bile acid metabolism. It also identified a cluster of nine bacterial species and nine fecal metabolites yielding excellent discriminatory power for new-onset T1D. It also showed that human T1D gut microbiota induced elevated fasting glucose levels and reduced insulin sensitivity when transplanted to antibiotic-treated mice; and butyrate and LPS had protective and destructive effects, respectively, on glucose metabolism and islet structure and function in a mouse model of streptozotocin-induced diabetes.

Overall, these data combined with previous findings support a role for specific gut bacteria and metabolites as novel diagnostic and therapeutic targets for T1D (3). One potential therapeutic option could be blocking LPS production and entrance into the blood.

References: 1. Quattrin T, Mastrandrea LD, Wlaker LSK. Type 1 diabetes. Lancet. 2023;401(10394):2149–2162. 2. Rampanelli E, Nieuwdorp M. Gut microbiome in type 1 diabetes: the immunological perspective. Expert Rev Clin Immunol. 2023;19(1):93–109. 3. Del Chierico F, Rapini N, Deodati A, Matteoli MC, Cianfarani S, Putignani L. Pathophysiology of type 1 diabetes and gut microbiota role. Int J Mol Sci. 2022;23(23):14650.