- Author
-
B.W. Haak
- Title
- Intestinal microbiota and host defense in systemic infectious diseases
- Subtitle
- Translational studies in the healthy and the ill
- Supervisors
- Co-supervisors
-
T. van der Poll
- Award date
- 11 December 2020
- Number of pages
- 373
- ISBN
- 9789463759045
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
In recent years, research interest in understanding the role that the intestinal microbiota plays in human health has increased exponentially. However, few findings from preclinical models have been translated into clinically meaningful microbiota-targeted therapies for treating physicians. This thesis has aimed to translate the findings obtained through preclinical animal models into human cohort and intervention studies linking antibiotic-induced disturbances of the intestinal microbiome to altered function of the innate immune system. We hypothesized that the collateral effects of disruptions of these commensal intestinal microorganisms contribute to increased susceptibility to systemic infections.
Using clinical cohorts and human adult volunteer studies, we were able to demonstrate that alterations of the gut microbiome, specifically a loss of anaerobic butyrate-producing bacteria, are associated with a loss of protection against infectious agents. In addition, we have shown that intestinal bacterial composition is indeed linked with direct innate immune responses. Finally, we show that antibiotic-induced modulation of the bacterial component of the microbiome has implications extending beyond this kingdom alone, enabling the overgrowth of potentially invasive and pathogenic fungi and viruses.
While these findings show promise that specific intestinal bacteria are associated with protection against infections, it is clear that we are only beginning to understand the overarching mechanisms by which such microbial metabolites and micro-organisms influence the immune system. Therefore, future studies aimed at elucidating the underlying mechanisms of action will be vital to understanding how best to improve innate immune responses and induce protection against systemic infectious diseases. - Persistent Identifier
- https://hdl.handle.net/11245.1/ca027e6a-676a-4265-bc79-31fd21d80fec
- Downloads
-
Thesis (complete)
Front matter
1: General introduction
2: Effect of antibiotic-mediated microbiome modulation on rotavirus vaccine immunogenicity; A human randomized-control proof-of-concept trial
3: Long-term impact of oral vancomycin, ciprofloxacin and metronidazole on the gut microbiota in healthy humans
4: Altered patterns of compositional and functional disruption of the gut microbiota in typhoid fever and non-typhoidal febrile illness
5: Impact of gut colonization with butyrate producing microbiota on respiratory viral infection following allo-HCT
6: Disruptions of anaerobic gut bacteria are associated with stroke and post-stroke infection
7: Intestinal microbiota profiles are coupled with altered monocyte function following community-acquired pneumonia hospitalization
8: Nasopharyngeal bacterial and viral markers are predictive of lower respiratory tract infection in an elderly cohort
9: Intestinal transkingdom analysis on the impact of antibiotic perturbation in health and critical illness
10: Intestinal bacteria and viruses predict length of hospital stay in community-acquired pneumonia
11: Uncovering hidden antimicrobial resistance patterns within the hospital microbiome
12: Fecal microbiota transplantation in the ICU: perspectives on future implementations
13: The differing roles of lactobacilli in critical illness
14: Summary
15: Nederlandse samenvatting
List of contributing authors; List of publications; Portfolio; Dankwoord; About the author
- Supplementary materials
Disclaimer/Complaints regulations
If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library, or send a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible.