Leiden University Scholarly Publications

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Katiraei, S. (2023)

Role of intestinal microbiota in cardio-metabolic diseases

Doctoral Thesis
The global obesity pandemic is one of the most significant long-term challenges for healthcare in the current era. Obesity is strongly associated with disrupted glucose and lipid metabolism, a pro-inflammatory state of the immune system, and has a causal role in the development of cardiometabolic diseases. The medical science is challenged to find new targets in the fight against this worldwide silent pandemic.We investigated how the gut microbiota influences local and systemic lipid metabolism and immune system of the host and the relationship to pathophysiology of atherosclerosis. The central question was "Does the gut microbiota have a anti-atherogenic potential?" Our studies have shown that oral administration of the bacterium A. muciniphila positively influences the host's lipid metabolism. In addition, oral administration of this bacterium triggers an anti-inflammatory immune response. These findings suggest that A. muciniphila has anti-atherogenic potential. Furthermore,...Show moreThe global obesity pandemic is one of the most significant long-term challenges for healthcare in the current era. Obesity is strongly associated with disrupted glucose and lipid metabolism, a pro-inflammatory state of the immune system, and has a causal role in the development of cardiometabolic diseases. The medical science is challenged to find new targets in the fight against this worldwide silent pandemic.We investigated how the gut microbiota influences local and systemic lipid metabolism and immune system of the host and the relationship to pathophysiology of atherosclerosis. The central question was "Does the gut microbiota have a anti-atherogenic potential?" Our studies have shown that oral administration of the bacterium A. muciniphila positively influences the host's lipid metabolism. In addition, oral administration of this bacterium triggers an anti-inflammatory immune response. These findings suggest that A. muciniphila has anti-atherogenic potential. Furthermore, we provided critical insights into two commonly accepted and widely used research methods in cardiometabolic and microbiome research, namely Bone Marrow Transplantation (BMT) and 16S rRNA sequencing. These insights should be taken into account in the research design and interpretation of the research data when applied. In another study, we demonstrated that the gut microbiota increases the cytokine reactions of immune cells after BMT. This phenotype can be transferred to immune cells of healthy controls through Fecal Microbiota Transplantation, implying that this phenotype is independent of BMT-induced gut damage, leaky gut syndrome, and microbiota-mediated. In summary, our studies show that the gut microbiota has anti-atherogenic potential by playing a causal role in the modulation of lipid metabolism and the host's immune system.Show less
Lipid metabolism
Immunity
Microbiota
Akkermansia muciniphila
16S Sequencing
All authors
Katiraei, S.
Supervisor
Willems van Dijk, J.A.P.
Co-supervisor
Harmelen, V.J.A. van; Berbée, J.E.P.
Committee
Rensen, P.C.N.; Nieuwdorp, M.; Wang, Y.; Kersten, A.H.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2023-03-30
ISBN (print)
9789491837531