The Role of Gut Microbiota in Type 2 Diabetes Mellitus and Alzheimer's Disease: The cost of an over-exaggerated immune response?

Agnes Amanda Vesth Rasmussen & Mie Lykke Jeppesen

Studenteropgave: Kandidatprojekt

Abstrakt

The gut microbiota (GM) has in recent years become a large field of research revealing that the GM plays a role in both health and diseases, Alzheimer’s Disease (AD), and Type 2 Diabetes mellitus (T2DM) being two of them. Main hallmarks of the two diseases are amyloidβ (Aβ) depositions and insulin resistance (IR), respectively. Recent studies have shown that different factors like chronic inflammation and IR correlate in the pathogenesis of the two diseases. In the present paper coinciding factors are investigated, including how they are affected by the GM. As a result of examining novel research, we propose a hypothesis where AD and T2DM are induced by an over-exaggerated immune response reacting to a dysbiotic GM. We theorize that both IR and Aβ serve as defense mechanisms, although, the biological functions of Aβ and IR are dependent on physiological conditions, e.g. chronic inflammation. During normal physiological state, IR can protect the cells from glucolipotoxicity and formation of reactive oxygen species (ROS) due to hyperglycemia as seen in T2DM. Aβ has recently been proposed to function as an antimicrobial peptide (AMP) and might be recruited by Toll Like Receptor (TLR) 4 activation by lipopolysccharides (LPS) and free fatty acids (FFAs), which are observed in high amounts during e.g. GM dysbiosis and obesity. However, during chronic activation of TLR4, two issues arise. For one, Aβ is not properly cleared and contributes to neurodegeneration in AD. Secondly, IR inhibits cellular glucose influx leading to hypoglycemia. Furthermore, there are several positive feedback mechanisms involved after chronic inflammation is induced due to a dysbiotic GM. First TLR4 activation triggers Aβ oligomerization which in turn triggers TLR4 activation. Secondly, IR and Aβ oligomers (AβO) reinforce each other. Altogether, this indicates that T2DM and AD are results of short term protective solutions to chronic problems.

UddannelserMedicinalbiologi, (Bachelor/kandidatuddannelse) Kandidat
SprogEngelsk
Udgivelsesdato21 dec. 2017
Antal sider47
VejledereLotte Jelsbak

Emneord

  • Diabetes
  • Alzheimer's Disease
  • Type 2 Diabetes Mellitus
  • TLR4
  • Inflammation
  • Insulin Resistance
  • Gut Microbiota
  • Dysbiosis
  • LPS
  • FFA
  • Dementia