Mice with Streptozotocin-Induced Hyperglycemia are Susceptible to Invasive Enteric Bacterial Infection

Abstract

SUMMARY: Diabetes mellitus and diarrhea are becoming increasingly burdensome worldwide, particularly in developing countries such as India. Diabetic patients are susceptible to infection with pathogenic bacteria, particularly those causing invasive enteric infections. In this study, we observed changes in the pathophysiological features of mice with streptozotocin-induced hyperglycemia. In our experiments, both hyperglycemic and control mice were infected with pathogenic enteric bacteria-nontyphoidal Salmonella, Shigella flexneri, or Vibrio parahaemolyticus. Morbidity, mortality, and bacterial load were all higher in the diabetic mice than in the control mice, and the phagocytic and bactericidal activities of peritoneal macrophages isolated from hyperglycemic mice were lower than they were in the controls. We hypothesize that hyperglycemia leads to a downregulation of the innate immune response, which in turn increases vulnerability to enteric bacterial infection.

Insulin Modulates Inflammatory Cytokine Release in Acute Stages and Augments Expression of Adhesion Molecules and Leukocytes in Lungs on Chronic Stages of Paracoccidioidomycosis

“…These results could help to explain the high susceptibility presented by T1D mice to Pb18 observed in previous studies (16). These data also corroborate previous findings in animal models as macrophages from hyperglycemic mice presented reduced phagocytic activity against Salmonella typhimurium (34), and diabetic rat neutrophils were also less efficient against Candida albicans yeasts (35). These phagocytic dysfunctions in T1D were associated with changes in cell metabolism and in insulin levels.…”

A murine model of diarrhea, growth impairment and metabolic disturbances withShigella flexneriinfection and the role of zinc deficiency

“…Several efforts have been made to model shigellosis in vivo. 8,12,[17][18][19][20] However, unnatural inoculum administration routes and the absence of common disease outcomes are limitations of current models. In contrast, by using prior antibiotic treatment, we have been able to reproduce common human clinical effects through oral administration of S. flexneri inoculum, that are also affected by dietary zinc deficiency.…”

“…10 In addition, many efforts have been made for developing a robust mouse model that could allow oral administration of the inoculum, but only few studies have been published and have not yet fully characterized host responses and common clinical outcomes. 11,12 A clearer understanding of the virulence mechanisms among the different Shigella species is warranted to design better interventions, such as vaccines. 13,14 Moreover, the poor understanding of the influence of environmental factors on the virulence of Shigella infection is well documented.…”

Glucose alters the symbiotic relationships between gut microbiota and host physiology

“…People with diabetes are more likely to develop an infection when exposed to Salmonella enteritidis during a nosocomial outbreak (41). In mice, streptozotocin-induced hyperglycemia increased susceptibility to numerous invasive enteric infections, including Salmonella, Shigella flexneri, and Vibrio parahemolyticus compared with nondiabetic mice (24). Similarly, limiting glucose availability to bacteria may mitigate systemic infection and reduce virulence as shown in a model of Salmonella typhimurium infection (35).…”