Henrik Rasmussen

• Vestad, Beate; Hanzely, Petra; Karaliūtė, Indrė; Ramberg, Oda Helgesen; Skiecevičienė, Jurgita & Lukoševičius, Rokas [Vis alle 12 forfattere av denne artikkelen] (2025). Modulation of Dextran Sodium Sulfate-Induced Colitis in Germ-Free Mice by Enterococcus faecalis Monocolonization. Microorganisms. 13(12). doi: 10.3390/microorganisms13122864. Fulltekst i vitenarkiv Vis sammendrag

  Inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis (UC), are characterized by chronic gastrointestinal inflammation and involve complex interactions of genetic, environmental, and immune factors. Enterococcus faecalis, a gut commensal bacterium, has been implicated in IBD pathogenesis. This study investigated the effects of monocolonization with a UC-derived E. faecalis strain on acute dextran sulfate sodium (DSS)-induced colitis in germ-free (GF) mice, focusing on epithelial injury, inflammatory markers, hematologic indices, and bacterial translocation. In DSS-treated mice, monocolonization was associated with modest and mixed effects, including a higher colitis-related disease activity score, reduced anemia, increased fecal albumin and a trend towards reduced fecal calprotectin. Despite translocation of E. faecalis to mesenteric lymph nodes, no systemic dissemination was observed. Histological analysis revealed broadly similar inflammatory patterns between DSS-treated groups, with slightly more epithelial injury observed in colonized mice. These findings suggest that E. faecalis may influence discrete aspects of DSS injury in a strain-dependent and context-specific manner, rather than broadly altering overall disease severity. This study highlights the utility of GF models for examining strain-specific host–microbe interactions and underscores that individual bacterial isolates may exert heterogeneous and selective effects on acute colitis. Further research is needed to elucidate these complex mechanisms.

• Hanzely, Petra; Holm, Kristian; Bjørnholt, Jørgen Vildershøj; Melum, Espen; Hov, Johannes Espolin Roksund & Rasmussen, Henrik (2025). Efficacy of oral and rectal administration of human faecal microbiota transplant (FMT) in human microbiota-associated mouse models. Scientific Reports. 15(1), s. 1–10. doi: 10.1038/s41598-025-32072-0. Fulltekst i vitenarkiv Vis sammendrag

  The gut microbiome has gained significant interest due to its association with immune dysregulation, allergies, autoimmune conditions, metabolic disorders, and inflammation-associated malignancies. Understanding underlying mechanisms requires appropriate in vivo models, such as human microbiota-associated mouse models to study the microbiota–host interactions. This study compared the efficacy of oral and rectal administration of human faecal microbiota transplant (FMT) from a single donor in C57BL/6J germ-free mice as these methods are often used interchangeably. Using 16S rRNA sequencing, we quantified colonisation efficacy in luminal and tissue samples from orally- (n = 6) and rectally- (n = 6) colonised mice. We detected 84 genera in the FMT sample, 17 of which were not transferred at all, while additional 7 genera were found exclusively in rectally-colonised mice. A significantly higher proportion of amplicon sequence variants (ASVs) (33% vs. 26%; P < 0.05) and genera (32% vs. 25%; P < 0.05) were absent in orally- compared to rectally-colonised group. Some taxa showed different relative abundances in human vs. mouse samples (e.g. Alistipes and Bacteroides relatively more abundant in mice while Faecalibacterium considerably decreased). Beta diversity analysis revealed greater similarity between FMT and tissue samples irrespective of the administration route, with distinct separation of the tissue and luminal samples. Overall, rectal administration yielded more overlapping genera and ASVs with FMT, highlighting that it could have advantages compared with oral administration for microbiota establishment studies

• Oldereid, Tine Simensen; Jiang, Xiaojun; Øgaard, Jonas Daniel Sjøberg; Schrumpf, Elisabeth; Bjørnholt, Jørgen & Rasmussen, Henrik [Vis alle 7 forfattere av denne artikkelen] (2023). Microbial exposure during early life regulates development of bile duct inflammation. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 59(2), s. 192–201. doi: 10.1080/00365521.2023.2278423. Fulltekst i vitenarkiv Vis sammendrag

  Objectives The early life microbiome has been linked to inflammatory diseases in adulthood and a role for the microbiome in bile duct inflammation is supported by both human and murine studies. We utilized the NOD.c3c4 mouse model that develops a spontaneous immune-driven biliary disease with a known contribution of the microbiome to evaluate the temporal effects of the early life microbiome. Materials and methods Germ-free (GF) NOD.c3c4 mice were conventionalized into a specific pathogen free environment at birth (conventionally raised, CONV-R) or at weaning (germ-free raised, GF-R) and compared with age and gender-matched GF and conventional (CONV) NOD.c3c4 mice. At 9 weeks of age, liver pathology was assessed by conventional histology and flow cytometry immunophenotyping. Results Neonatal exposure to microbes (CONV-R) increased biliary inflammation to similar levels as regular conventional NOD.c3c4 mice, while delayed exposure to microbes (GF-R) restrained the biliary inflammation. Neutrophil infiltration was increased in all conventionalized mice compared to GF. An immunophenotype in the liver similar to CONV was restored in both CONV-R and GF-R compared to GF mice displaying a proportional increase of B cells and reduction of T cells in the liver. Conclusions Microbial exposure during early life has a temporal impact on biliary tract inflammation in the NOD.c3c4 mouse model suggesting that age-sensitive interaction with commensal microbes have long-lasting effects on biliary immunity that can be of importance for human cholangiopathies.

• Nordén, Einar Sjaastad; Veras, Ioanni; Yadav, Prakash; Løken, Kari Gulbrandsen; Dishington, Hilde & Thorstensen, Christian [Vis alle 8 forfattere av denne artikkelen] (2023). Clinical efficacy of buprenorphine after oral dosing in rats undergoing major surgery. Laboratory Animals. ISSN 0023-6772. doi: 10.1177/00236772231178417. Fulltekst i vitenarkiv Vis sammendrag

  Serum corticosterone, serum buprenorphine, body weight change, consumption of food and water and behaviour-based pain assessment were measured in catheterised and non-catheterised male Wistar rats undergoing myocardial infarct (MI) surgery under general anaesthesia following buprenorphine dosing by subcutaneous (Bup-SC, 0.05 mg/kg) and oral (Bup-O, 0.4 mg/kg) routes. Buprenorphine was dosed subcutaneously at half an hour before and 8, 16 and 24 hours after surgery (Bup-SC), orally at one hour before surgery (Bup-O1) or at one hour before and 12 hours after surgery (Bup-O2) in catheterised rats and at one hour before and 24 hours after surgery (Bup-O24) in non-catheterised rats. Serum corticosterone, body weight changes and food and water consumption were not significantly different between treatments in catheterised rats. Bup-SC resulted in rapidly decreasing serum concentrations below the clinically effective concentrations (1 ng/mL) already at two hours after the first dose. Bup-O provided significantly higher and slowly decreasing serum concentrations, at or above clinically effective concentrations, for 24 hours (Bup-O1) and 42 hours (Bup-O2) after surgery. In non-catheterised rats, body weight development and food consumption were significantly higher in Bup-O24 rats compared to Bup-SC rats. The results indicate that a SC buprenorphine dose of 0.05 mg/kg every eight hours provides long periods of serum concentrations below clinically effective levels, and that a higher dose and/or more frequent dosage are required to provide stable serum concentrations at or above clinically effective levels. A single oral buprenorphine dose of 0.4 mg/kg provides clinically effective and stable serum concentrations for 24 hours in rats after MI surgery.

• Oldereid, Tine Simensen; Jiang, Xiaojun; Nordhus, Kathrine Sivertsen; Ponzetta, Andrea; Bjørnholt, Jørgen & Björkström, Niklas K. [Vis alle 8 forfattere av denne artikkelen] (2023). Role of bacteria and microbial metabolites in immune modulation during early life. Scandinavian Journal of Immunology. ISSN 0300-9475. doi: 10.1111/sji.13336. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Host–microbiome interplay from birth is essential for immune imprinting and tuning. Live gut microbes and microbial‐derived metabolites regulate the development and modulation of the immune system, but whether microbial metabolites solely are sufficient to induce immune maturation remains unclear. Sterile faecal filtrates (FFT) were generated from murine gut contents. Newborn germ‐free (GF) mice were treated twice daily with FFT (GF‐FFT) or saline (GF‐NaCl) from post‐natal day 5 until 4 weeks of age. A third group of GF neonates were conventionalized by the transfer of caecal microbiota with live gut microbes. Host immune compartments were comprehensively immunophenotyped and systemically analysed in all available immune‐related organs using flow cytometry. Oral FFT was associated with reduced survival among neonates (n = 7/19; 36.8% mortality), while saline treatment was well tolerated (n = 1/17, 5.9% mortality). Four‐week‐old FFT‐treated pups were comparable in body weight to GF‐NaCl, and the major B‐cell, conventional T‐cell and unconventional T‐cell subsets were unchanged from saline‐treated mice. Live bacteria administered during early life induced clear changes in proportions of B cells, T cells and T‐cell subsets in all mucosal tissues and secondary lymphoid organs compared to GF‐FFT, including restoration of intestinal natural killer T (NKT) cells with characteristics similar to conventional pups. Our findings show that oral administration of a FFT made of microbial metabolites, antigens and bacteriophages alone is insufficient to induce normal immune development elicited by the presence of live bacteria. Reduced survival during neonatal FFT treatment suggests a potential bioactive attribute of sterile faecal filtrates.

• Inngjerdingen, Kari Tvete; Langerud, Beathe Kiland; Rasmussen, Henrik; Olsen, Trude Karin; Austarheim, Ingvild & Grønhaug, Tom Erik [Vis alle 10 forfattere av denne artikkelen] (2013). Pectic polysaccharides isolated from Malian medicinal plants protect against Streptococcus pneumoniae in a mouse pneumococcal infection model. Scandinavian Journal of Immunology. ISSN 0300-9475. 77(5), s. 372–388. doi: 10.1111/sji.12047. Fulltekst i vitenarkiv
• Pucaj, Kresimir; Rasmussen, Henrik; Møller, Mona & Preston, Tom (2011). Safety and toxicological evaluation of a synthetic vitamin K2, menaquinone-7. Toxicology Mechanisms and Methods. ISSN 1537-6516. 21(7), s. 520–532. doi: 10.3109/15376516.2011.568983. Fulltekst i vitenarkiv
• Hansen, Jitka Stilund; Alberg, Torunn; Rasmussen, Henrik; Løvik, Martinus & Nygaard, Unni Cecilie (2011). Determinants of Experimental Allergic Responses: Interactions Between Allergen Dose, Sex and Age. Scandinavian Journal of Immunology. ISSN 0300-9475. 73(6), s. 554–567. doi: 10.1111/j.1365-3083.2011.02529.x. Fulltekst i vitenarkiv
• Wistrand, Lars-G; Rogstad, Astri; Hagelin, Gunnar; Roed, Line; Oulie, Inger & Gram, Andreas [Vis alle 12 forfattere av denne artikkelen] (2010). GE-145, a new low-osmolar dimeric radiographic contrast medium. Acta Radiologica. ISSN 0284-1851. 51(9), s. 1014–1020. doi: 10.3109/02841851.2010.509739. Fulltekst i vitenarkiv
• Chai, Chun-Ming; Rasmussen, Henrik; Eriksen, Morten; Hvoslef, Anne-Marie; Evans, Paul & Newton, Ben B [Vis alle 7 forfattere av denne artikkelen] (2010). Predicting cardiotoxicity propensity of the novel iodinated contrast medium GE-145: Ventricular fibrillation during left coronary arteriography in pigs. Acta Radiologica. ISSN 0284-1851. 51(9), s. 1007–1013. doi: 10.3109/02841851.2010.504743. Fulltekst i vitenarkiv

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• Knudsen, Siri; Brønstad, Aurora Margrethe; Flatekval, Gro Furset; Handegård, Karin Westereng; Persson, David Weman & Ramstad, Anne [Vis alle 8 forfattere av denne artikkelen] (2024). Feil om bruk av forsøksdyr – Norge er ikke en versting. Norsk veterinærtidsskrift. ISSN 0332-5741. Fulltekst i vitenarkiv
• Langerud, Beathe Kiland; Inngjerdingen, Kari Tvete; Rasmussen, Henrik; Olsen, Trude Karin; Austarheim, Ingvild & Aaberge, Ingeborg Sundsvalen [Vis alle 9 forfattere av denne artikkelen] (2011). Pectic Polysaccharides Isolated from Malian Medicinal Plants can Prevent Bacteraemia and Clinical Symptoms in a Mouse Pneumococcal Infection Model. Scandinavian Journal of Immunology. ISSN 0300-9475. 73(4), s. 390–390. Fulltekst i vitenarkiv
• Oldereid, Tine Simensen & Rasmussen, Henrik (2026). Microbial exposures during early life. Modulatory effects on immune system development and long-term impact on biliary inflammation in mice. Universitetet i Oslo. ISSN 9788234807800. Fulltekst i vitenarkiv Vis sammendrag

  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.

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