Project 05

Gut infection modulating glucose metabolism

• Principial Investigators:
  • TUD: Nikolaos Perakakis & Geltrude Mingrone
  • UZH: Claudia Cavelti-Weder
• Students:
  • TUD: Anushka Dayal (1st year-PhD student)

  • UZH: Seyed Esmaeil Ahmadi (1st year-PhD student), Elisa Braun (1st year-PhD student)

Background: We have recently demonstrated that the gut plays a crucial role in regulating insulin sensitivity by affecting hepatic gluconeogenesis and muscle insulin resistance (Mingrone group). Additionally, gut-secreted hormones such as incretins are involved in the regulation of insulin secretion, appetite, energy homeostasis and glucose metabolism (Perakakis group). Furthermore, we have shown that gut inflammation, characterized by the presence of pro-inflammatory intestinal macrophages, plays an important role in metabolic diseases such as obesity by affecting glucose metabolism (Cavelti-Weder group). We could show that this shift towards inflammatory intestinal macrophages is linked to glucose homeostasis as colon-specific macrophage depletion by intrarectal administrations of clodronate liposomes led to improved glucose tolerance.

Aims: We aim to test whether gut inflammatory responses elicited either by an infectious or non-infectious agent are able to regulate glucose and lipid homeostasis, thus contributing to the development or aggravation of metabolic diseases and specifically to progression of hyperglycaemia.

Added value through the collaboration between Dresden & Zurich: Dresden groups 
(Perakakis, Mingrone) have great experience with clinical studies involving patients with metabolic diseases and in the evaluation of glucometabolic status in different energy states. The two groups will join forces and will be responsible for the clinical studies of the project. The Zurich group has great experience on immunologic mouse studies, focusing on gut inflammation and will be responsible for performing the mouse studies.
Additionally the Zürich group will advise Dresden groups and contribute to the immunologic phenotyping of the clinical studies. Combining these areas of expertise will provide important knowledge on the possible involvement of the inflammatory state of the gut due to infectious diseases in the regulation of glucose homeostasis.

Synergies: We have already interacted with projects 7 and 8 and plan to use the same clinical study that will involve lean and obese individuals at different glycemic states (diabetes, prediabetes, normoglycemic) with or without NAFLD, to address several aims of the three projects. This will provide a deep phenotyping of the study population and allow to compare / combine findings from the three projects and especially in our case with project 7 that assesses gut-liver axis with focus on NAFLD. Additionally, we are looking forward to collaborate with projects 1, 2 and 3 as described in their respective synergies.