Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Axel Kornerup Hansen, University of Copenhagen, Denmark
- Second opponent: Associate Professor Martin Sundqvist, Örebro University, Sweden
- Third member and chair of the evaluation committee: Professor Gunnveig Grødeland, University of Oslo
Chair of the Defence
Professor II Erik Sveberg Dietrichs, University of Oslo
Principal Supervisor
Associate Professor Henrik Rasmussen, University of Oslo
Summary
Early-life interplay between the developing immune system and the gut microbiota shape immunity and may influence the risk of later immune-mediated disease, including bile duct diseases. This thesis explores how host-microbiota interactions and exposures to non-viable microbial components during early life influence immune development and inflammation.
This work is based on experimental studies in germ-free mice with controlled microbial colonisation. Data include histopathological analyses and immunophenotyping of intestinal and systemic immune compartments.
This thesis defines a critical postnatal time window during which microbial exposure affects later biliary inflammation. A germ-free period immediately after birth significantly reduces the severity of bile duct inflammation later in life, indicating a modulatory effect of early-life microbial exposures. The work further explores whether non-viable microbial components can substitute for live bacteria in shaping long term immune responses. Reproducible methods were established for producing bacteria-free, sterile-filtered gut lysates containing microbial antigens, host proteins and bacteriophages. While these lysates induced mild and transient immune activation after systemic administration, oral administration to newborn germ-free mice did not induce immune responses in the intestinal mucosa, gut-draining lymph nodes, or secondary lymphoid organs.
These results indicate that early postnatal exposure to gut microbiota is important for immune regulation and influences long-term severity of biliary inflammation. In contrast, microbial components in the absence of live bacteria, appear insufficient to drive normal immune development.
Additional information
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