Sodium Fusidate Ameliorates the Course of Diabetes Induced in Mice by Multiple Low Doses of Streptozotocin

Lack of effect of intermittently administered sodium fusidate in patients with newly diagnosed type 1 diabetes mellitus: the FUSIDM trial

“…Our demonstration in the present study of the inability of fusidin to exert a favourable effect on the course of newly diagnosed type 1 diabetes is in striking contrast to preclinical studies carried out by ourselves and others using animal models of the disease, such as the NOD mouse [4], the diabetes-prone BB rat [5,6] and the mouse made diabetic with MLDSZ [7], which all benefited from fusidin prophylaxis. The effect of fusidin in these three models of human type 1 diabetes was particularly encouraging for possible translation to the clinical setting, as inhibition of diabetes development in all these models is not achieved by the T-cell immunosuppressant CyA, which has shown a moderate effect in patients with type 1 diabetes [1].…”

“…The drug downregulates IL-2, IFN-γ and IL-1 secretion and also inhibits the lymphocyte costimulatory activity of IL-6 and IL-1 [2,3]. The interference of fusidin with the cytokine network has been ascribed to its capacity to protect beta cells from destruction and to its observed beneficial effects in the three most commonly used preclinical models of human type 1 diabetes: the NOD mouse [4], the DP-BB rat [2,5,6] and the mouse made diabetic with multiple low doses of streptozotocin (MLDSZ) [7]. These preclinical studies were corroborated by the beneficial effects of fusidin treatment in an open study conducted in newly diagnosed type 1 diabetes patients [8].…”

Diabetes preventive gluten‐free diet decreases the number of caecal bacteria in non‐obese diabetic mice

“…Thus, high diabetes incidence in NOD colonies depends on the quality of the microbiology protecting barrier in animal facilities, [7,8] and several infections have been reported to prevent diabetes in NOD mice [6,9,28]. Supporting evidence may also be found in the fact that fusidic acid, an antibiotic that targets Gram-positive bacteria, reduces incidence of diabetes in both in BB rats and in the streptozotocin mouse model [13][14][15]. The indigenous gut microflora has several functions, but two aspects of the presence of the microflora at the gut mucosa may be relevant to the disease protective effect.…”

“…In both spontaneously diabetic BB rats [13,14] and streptozotocin diabetic mice [15], a reduced incidence has been described after treatment with the immunomodulator fusidic acid, the sodium salt of which, fusidin, is used as an anti-Gram-positive antibiotic. Although the impact of fusidic acid on diabetes has mainly been explained as a direct effect on the immune system, the anti-diabetogenic effect may also be thought to be exhibited by the antibiotic effect.…”

Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice

“…The marked decrease in blood insulin levels and in the proportion of insulin-expressing pancreatic cells indicates that diabetes results from a deficit in insulin production. The lack of pancreatic inflammatory infiltrates in hyperglycemic animals ( Figure 2, E-G) and the inability of the immunosuppressant sodium fusidate to lower the glycemia of hyperglycemic DKO mice at a dose known to reduce murine inflammatory diabetes (25) argue against an autoimmune nature of the diabetes (data not shown). The presence of steatorrhea, the decrease in serum amylase activity, as well as the histological findings, indicate a concomitant exocrine insufficiency.…”