Pharmacologic inhibition of glycolysis prevents the development of lupus by altering the gut microbiome in mice

Ahmed S. Elshikha, Yong Ge, Josephine Brown, Nathalie Kanda, Mojgan Zadeh, Georges Abboud, Seung Chul Choi, Gregg Silverman, Timothy J. Garrett, William L. Clapp, Mansour Mohamadzadeh, Laurence Morel

Producción científica: Articlerevisión exhaustiva

1 Cita (Scopus)

Resumen

Gut dysbiosis has been associated with lupus pathogenesis, and fecal microbiota transfers (FMT) from lupus-prone mice shown to induce autoimmune activation into healthy mice. The immune cells of lupus patients exhibit an increased glucose metabolism and treatments with 2-deoxy-D-glucose (2DG), a glycolysis inhibitor, are therapeutic in lupus-prone mice. Here, we showed in two models of lupus with different etiologies that 2DG altered the composition of the fecal microbiome and associated metabolites. In both models, FMT from 2DG-treated mice protected lupus-prone mice of the same strain from the development of glomerulonephritis, reduced autoantibody production as well as the activation of CD4+ T cells and myeloid cells as compared to FMT from control mice. Thus, we demonstrated that the protective effect of glucose inhibition in lupus is transferable through the gut microbiota, directly linking alterations in immunometabolism to gut dysbiosis in the hosts.

Idioma originalEnglish (US)
Número de artículo107122
PublicacióniScience
Volumen26
N.º7
DOI
EstadoPublished - jul 21 2023

ASJC Scopus subject areas

  • General

Huella

Profundice en los temas de investigación de 'Pharmacologic inhibition of glycolysis prevents the development of lupus by altering the gut microbiome in mice'. En conjunto forman una huella única.

Citar esto