Johannes Espolin Roksund Hov

• Rønneberg, Jørgen Dybevik; Chung, Brian K.; Xiaojun, Jiang; Elias, Joshua E.; Karlsen, Tom Hemming & Kaneider, Nicole C. [Vis alle 8 forfattere av denne artikkelen] (2026). GPR35-positive mast cells are enriched in primary sclerosing cholangitis and show an enhanced secretory phenotype. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. doi: 10.1080/00365521.2026.2731959. Fulltekst i vitenarkiv
• Molinaro, Antonio; Braadland, Peder Rustøen; Carpino, Guido; Carreras, Alba; Nikolaidis, Marios & Hanzely, Petra [Vis alle 40 forfattere av denne artikkelen] (2026). Gut microbiota-derived imidazole propionate promotes primary sclerosing cholangitis via p38 signalling. Nature Metabolism. 8(9), s. 1910–1925. doi: 10.1038/s42255-026-01600-1. Fulltekst i vitenarkiv Vis sammendrag

  Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the bile ducts that can lead to biliary cancer and end-stage liver disease. PSC is associated with inflammatory bowel disease and an altered gut microbiota. However, the molecular mechanisms underlying gut–liver interactions in PSC remain poorly characterized. Here we show that the gut microbiota-derived metabolite imidazole propionate (ImP) is a disease driver in PSC. Individuals with PSC have higher circulating ImP levels than individuals with related conditions, and high ImP levels predict reduced survival in PSC. Cholangiocytes exposed to ImP show activated mammalian target of rapamycin complex 1 (mTORC1) signalling and secrete pro-inflammatory and pro-fibrogenic factors. Chronic administration of ImP to mice induces liver inflammation and fibrosis through a p38-dependent mechanism, upstream of mTORC1. We propose that chronic exposure to ImP induces cholangiocyte injury, which alone or in concert with other factors causes clinical worsening of PSC. Therefore, targeting ImP production or signalling may represent therapeutic avenues in PSC.

• Lindstrøm, Jonas Christoffer; Gjerdrum, Hilde Synnøve Vollan; Brynildsrud, Ola Brønstad; Tannæs, Tone Møller; Kristoffersen, Anja Bråthen & Ricanek, Petr [Vis alle 17 forfattere av denne artikkelen] (2026). Exploring alterations in the gut resistome in medically treated inflammatory bowel disease patients. BMC Microbiology. 26, s. 1–13. doi: 10.1186/s12866-026-05101-9. Fulltekst i vitenarkiv
• Ullern, Andreas; Garborg, Kjetil Kjeldstad; Chauhan, Sudhir Kumar; Holm, Kristian; Bang, Corinna & Dunn, Claire [Vis alle 9 forfattere av denne artikkelen] (2026). Safety and efficacy of fecal microbiota transplantation in solid cancers resistant to immune checkpoint inhibitors: results of the MITRIC trial. Journal for ImmunoTherapy of Cancer (JITC). 14(7), s. 015122–015122. doi: 10.1136/jitc-2026-015122. Fulltekst i vitenarkiv Vis sammendrag

  Background Fecal microbiota transplantation (FMT) has shown promise in overcoming resistance to immune checkpoint inhibitors (ICIs) in early-phase cancer trials. We investigated the safety, feasibility and efficacy of FMT from ICI responders to patients with advanced cancers progressing on ICIs. Methods This was a single-arm phase IIa basket trial (MITRIC; NCT05286294 ) including patients with ICI-refractory cancer. Long-term ICI responders were used as FMT donors. Patients received FMTs in combination with ICIs; two FMT administrations (by colonoscopy) were scheduled before the first radiological evaluation after 6 weeks, and up to three later FMTs were allowed (by enema). Co-primary endpoints were the evaluation of FMT-related adverse events and objective response rate. Feasibility, clinical benefit rate, progression-free survival (PFS), overall survival (OS), implant engraftment, immune response and biomarkers were among the secondary objectives. Results The study enrolled 12 patients with melanoma (n=9), head and neck squamous cell carcinoma (HNSCC; n=1), renal cell carcinoma (n=1) or microsatellite instability-high pancreatic cancer (n=1). FMT was well tolerated, whereas immune-related toxicity occurred in 6/12 patients. All patients received the first FMT; 10/12 patients also underwent the second FMT. No objective responses were observed, while 5/12 patients recorded stable disease. Clinical benefit per-protocol (stable disease >6 months) was achieved in a patient with melanoma, who had regression of some lesions and remains alive after 33 months without further systemic treatment. Mixed responses with regression of some lesions were observed in another melanoma patient, and in a patient with HNSCC. The median PFS was 1.5 months, and median OS was 10.1 months. Sequencing of fecal samples indicated engraftment after the first FMT in most patients. Mass cytometry analysis of peripheral blood cells suggested that an activated and differentiated T-cell signature was associated with improved PFS and OS, while a naïve T-cell phenotype and a myeloid-dominant environment were unfavorable. CD14 + monocytes and serum interleukin-8 increased at group level over time. Conclusion FMT in combination with ICIs was safe and feasible in patients with advanced cancers, but with limited clinical activity. Further studies are required to clarify the potential benefit of FMT, identify the appropriate patient population and define criteria for donor selection. Trial registration number NCT05286294 .

• Stø, Kristine; Skagen, Karolina Ryeng; Bjerkeli, Vigdis; Ueland, Per Magne; Hov, Johannes Espolin Roksund & Trøseid, Marius [Vis alle 10 forfattere av denne artikkelen] (2026). Gut microbiota derived indoles are altered and associate with immune activation in moderate and severe carotid stenosis. Frontiers in Immunology. 17. doi: 10.3389/fimmu.2026.1796312. Fulltekst i vitenarkiv Vis sammendrag

  Background: An imbalance of gut microbiota, their metabolites as well as inflammatory mediators have been increasingly linked to both atherosclerosis and stroke. However, data on microbiota derived tryptophan and histidine metabolites in carotid atherosclerosis are scarce. Purpose: We investigated serum microbiota derived indoles, imidazole propionate (ImP) and trimethylamine N-oxide (TMAO), representing three distinct gut bacterial-related metabolites, in patients with carotid atherosclerosis compared with healthy controls with normal findings on carotid ultrasound. We aimed to examine their relation to plaque characteristics, immune activation markers and traditional cardiovascular risk factors. Methods: Thirty patients scheduled for carotid endarterectomy and 18 control subjects were included in this cross-sectional study. Carotid arteries were investigated with ultrasound. Indoles, ImP and TMAO were analyzed by liquid chromatography-tandem mass spectrometry, and Lipopolysaccharide (LPS) by a Limulus Amebocyte Lysate chromogenic assay. Results: Compared to controls, patients exhibited lower levels of indole-3-propionic acid (IPA) (p=0.004) and indole-3-acetic acid (IAA) (p = 0.030). In patients, higher levels of indole metabolites were associated with lower C-reactive protein. ImP and TMAO did not differ between patients and controls. Conclusion: Patients with carotid atherosclerosis exhibited reduced serum concentrations of IPA and IAA, thought to have anti-inflammatory effects, and increased inflammatory markers, possibly suggesting disruptions in the gut–vascular-immune axis.

• Myhre, Vegard; Kaarbø, Mari; Yang, Mingyi; Fevang, Børre; Sousa, Mirta Mittelstedt Leal de & Reims, Henrik Mikael [Vis alle 11 forfattere av denne artikkelen] (2026). Altered duodenal N6-methyladenosine levels in common variable immunodeficiency associate with duodenal microbiota. Frontiers in Immunology. 17. doi: 10.3389/fimmu.2026.1875823. Fulltekst i vitenarkiv
• Rønneberg, Jørgen Dybevik; Hjeltnes, Martine; Krieger, Josephine; Elias, Joshua E.; Stensland, Maria & Holm, Kristian [Vis alle 15 forfattere av denne artikkelen] (2026). An epithelial GPR35 isoform supports tumor-associated transcriptional and metabolic phenotypes. FEBS Letters. ISSN 0014-5793. s. 1–23. doi: 10.1002/1873-3468.70423.
• Braadland, Peder Rustøen; Ali, Ahmad H.; Puchas, Philip; Juran, Brian D.; Atkinson, Elizabeth J. & Schlicht, Erik M. [Vis alle 19 forfattere av denne artikkelen] (2026). Vitamin B6 predicts poor outcomes in geographically distinct populations with primary sclerosing cholangitis. Journal of Hepatology. ISSN 0168-8278. 85(2), s. 227–237. doi: 10.1016/j.jhep.2026.03.048. Fulltekst i vitenarkiv Vis sammendrag

  Background & Aims: Primary sclerosing cholangitis (PSC) has a variable disease course, complicating patient counseling and the timing of liver transplantation. Vitamin B6 deficiency predicts reduced liver transplantation-free survival in Scandinavian PSC cohorts. Here, we aimed to validate this observation in US and German PSC cohorts and to expand our analyses to include hepatic decompensation as a clinical outcome. Methods: Serum active vitamin B6 (pyridoxal 5’-phosphate [PLP]) was analyzed using liquid chromatography-tandem mass spectrometry in retrospective cohorts of people with PSC from Norway (n = 315), the USA (n = 756), and Germany (n = 149). Cox proportional hazards and Fine and Gray competing risk models were fitted to estimate the ability of PLP to predict liver transplantation-free survival and the cumulative incidence of hepatic decompensation, respectively. Results: The prevalence of vitamin B6 deficiency (PLP <20 nmol/L) in pre-transplant PSC was 50% in the Norway cohort and 25% in the USA cohort. The prevalence was higher among those with previous hepatic decompensation. The cumulative incidence of hepatic decompensation was higher in the USA cohort, while individuals in the Norway cohort were more commonly transplanted for indications other than hepatic decompensation. Despite differences in clinical practice, low PLP was consistently associated with shorter liver transplantation-free survival, and PLP added predictive value for liver transplantation or death from PSC over and above contemporary prediction models. Low PLP was also associated with a higher incidence of hepatic decompensation, which was mainly evident in the USA cohort, where decompensation was more common. The risk of both outcomes increased sharply within the deficient and marginal ranges and plateaued at sufficient PLP levels. Conclusions: Vitamin B6 deficiency is common in PSC outside Scandinavia and is consistently associated with poor outcomes across geographically distinct PSC populations. Impact and implications We previously showed that vitamin B6 deficiency is prevalent and associated with reduced liver transplantation-free survival in Scandinavian PSC cohorts. The current work shows that these observations generalize to a US population and that low vitamin B6 is also associated with the development of hepatic decompensation. Our results indicate that vitamin B6 provides incremental value for predicting outcomes in PSC across geographically distinct populations and that efforts to restore B6 sufficiency should be focused on the many individuals who present with vitamin B6 levels within the marginal-to-definitive deficiency range.

• Pati, Niladri Bhusan; Chung, Brian K.; Holm, Kristian; Sætre, Frank Ove; Reims, Henrik Mikael & Aasebø, Anders Theodor Michaelsen [Vis alle 12 forfattere av denne artikkelen] (2026). Ultra long-lived plasma cells in the human small intestine produce microbiota-reactive IgA antibodies. Beneficial Microbes. ISSN 1876-2883. s. 1–13. doi: 10.1163/18762891-bja00120. Fulltekst i vitenarkiv
• Stø, Kristine; Skagen, Karolina Ryeng; Holm, Kristian; Ueland, Thor; Vestad, Beate & Bjerkeli, Vigdis [Vis alle 10 forfattere av denne artikkelen] (2026). Oral Eikenella as a potential new biomarker of symptomatic carotid atherosclerosis. Journal of Oral Microbiology. 18(1). doi: 10.1080/20002297.2026.2613521. Fulltekst i vitenarkiv

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