Publications

Primary sclerosing cholangitis (PSC) is an idiopathic, progressive and incurable liver disease. Here, we aimed for systematic analyses of adaptive immune responses in PSC. By profiling the T cell repertoires of 504 individuals with PSC and 904 healthy controls, we identified 1,008 clonotypes associated with PSC. A substantial fraction of these clonotypes was restricted to known PSC human leukocyte antigen susceptibility alleles and known to target Epstein–Barr virus (EBV) epitopes. We further utilized phage-immunoprecipitation sequencing to determine antibody epitope repertoires of 120 individuals with PSC and 202 healthy controls, which showed a higher burden of anti-EBV responses in PSC than controls. EBV-specific monoclonal antibodies isolated from B cells in PSC livers corroborated convergent B and T cell responses against EBV. By analyzing electronic health records of >116 million people, we identified an association between infectious mononucleosis and PSC (odds ratio, 12; 95% confidence interval, 6.3–22.9), suggesting a link between EBV and PSC.

Environmental factors influence the risk of developing inflammatory bowel disease and its subsequent course. In this study, the authors demonstrate that specific environmental factors, including fruit and vegetable consumption, smoking, and appendectomy, are associated with the initial phenotype, activity, and severity of inflammatory bowel disease. Moreover, this study provides guidance for personalised patient counseling regarding modifiable risk factors.

Fatigue is a common and burdensome problem for patients with inflammatory bowel disease (IBD). Previous studies lack insight into the individual variability in fatigue severity and course over time, and the characteristics of patients at risk of severe and persistent fatigue. This study aimed to identify distinct groups of IBD patients based on their level and course of fatigue over 5 years. Subsequently, we examined the relationship between these trajectories, patient characteristics, and trajectories of perceived stress, sleep, and physical activity.

We included 16 fatigued patients with IBD in remission. Data were collected between December 2021 and March 2022, using semi-structured interviews. Template analysis was performed. We identified six themes regarding reasons why (not) to seek care for fatigue: (1) Cognitions about fatigue and coping with fatigue, (2) perceptions of fatigue-related care and previous care experiences, (3) perceived knowledge and behaviour of healthcare professionals, (4) physical and emotional well-being, (5) social relationships and support, and (6) practical factors. Regarding their care needs, patients reported a need for a holistic and person-centred care approach, with healthcare professionals actively addressing fatigue and offering care. They suggested a range of options for what care to offer, including eliminating physical causes of fatigue, discussing medication options, providing information on fatigue management, lifestyle support, psychological support, peer support and practical support.

There is a need for validated biosignatures capable of predicting a future diagnosis of inflammatory bowel disease. The authors of this text identified a blood protein signature that predicted Crohn’s disease as early as 16 years before its diagnosis and validated its high predictive capacity across multiple independent cohorts. The corresponding signature for preclinical ulcerative colitis had a lower, albeit significant, predictive ability.

The gut microbiome has been recognised as a key component in the pathogenesis of inflammatory bowel diseases (IBD), and the wide range of metabolites produced by gut bacteria are an important mechanism by which the human microbiome interacts with host immunity or host metabolism. High-throughput metabolomic profiling and novel computational approaches now allow for comprehensive assessment of thousands of metabolites in diverse biomaterials, including faecal samples. Several groups of metabolites, including short-chain fatty acids, tryptophan metabolites and bile acids, have been associated with IBD. In this Recent Advances article, the authors describe the contribution of metabolomics research to the field of IBD, with a focus on faecal metabolomics. They discuss the latest findings on the significance of these metabolites for IBD prognosis and therapeutic interventions and offer insights into the future directions of metabolomics research.

Nutrition has been acknowledged as crucial in IBD and is relevant to patients’ motives behind food choices, which are affected by health engagement (HE) and food involvement (FI). This study aimed to profile IBD patients according to their levels of health engagement and food involvement to identify patterns of different motives behind food choices, particularly regarding the use of food to regulate mood. A cross-sectional study was conducted with 890 Italian IBD patients who completed an online survey in April 2021. The authors measured health engagement, food involvement, motives behind food choices, emotional states, and food-related quality of life (Fr-QoL). K-means cluster analysis was performed to identify participants with similar levels of health engagement and food involvement. Four clusters were identified: “Health-conscious (high HE, low FI)”, “Balanced (high HE, high FI)”, “Hedonist (high FI, low HE)”, and “Careless (low FI, low HE)”. Clusters with high FI are inclined toward seeking pleasurable food, but when supported with high health engagement, individuals were less prone to use food to manage mood. Groups with higher health engagement demonstrated lower hospitalisation rates and relapses and better Fr-QoL. Profiling IBD patients regarding FI and HE could aid clinicians in identifying individuals at greater risk of maladaptive food-related behaviours.

Disrupted host-microbe interactions at the mucosal level are key to the pathophysiology of IBD. This study aimed to comprehensively examine crosstalk between mucosal gene expression and microbiota in patients with IBD. To study tissue-specific interactions, we perform transcriptomic (RNA-seq) and microbial (16S-rRNA-seq) profiling of 697 intestinal biopsies (645 derived from 335 patients with IBD and 52 from 16 non-IBD controls).

Inflammatory bowel diseases (IBDs) are chronic immune-mediated inflammatory diseases. A comprehensive overview of an IBD-specific antibody epitope repertoire is, however, lacking. Using high-throughput phage-display immunoprecipitation sequencing (PhIP-Seq), the authors of this paper identified antibodies against 344,000 antimicrobial, immune, and food antigens in 497 individuals with IBD compared with 1,326 controls.

Inflammatory bowel disease (IBD) comprises Crohn’s disease (CD), ulcerative colitis (UC), and IBD unclassified (IBDU). These chronic and incurable diseases of unknown etiology typically manifest during young adulthood and follow a heterogeneous disease course. Patients with IBD require continual monitoring and expensive treatments that result in significant direct and indirect societal and healthcare-related costs. The cause of IBD is unknown, though it is presumed to arise from a combination of environmental exposures and genetic susceptibility. The rapidly increasing incidence rates of IBD in the wake of industrialisation in traditionally low-incidence areas such as Asia, Africa, and Eastern Europe points toward environmental risk factors as pivotal. As of 2019, the global burden of IBD was nearly five million affected individuals. The prevalence of IBD in Australia, North America, and several European countries exceeds 0.3%.

Gut dysbiosis has been associated with impaired outcomes in liver and kidney transplant recipients, but the gut microbiome of lung transplant recipients has not been extensively explored. We assessed the gut microbiome in 64 fecal samples from end-stage lung disease patients before transplantation and 219 samples from lung transplant recipients after transplantation using metagenomic sequencing. To identify dysbiotic microbial signatures, we analyzed 243 fecal samples from age-, sex-, and BMI-matched healthy controls. By unsupervised clustering, we identified five groups of lung transplant recipients using different combinations of immunosuppressants and antibiotics and analyzed them in relation to the gut microbiome. Finally, we investigated the gut microbiome of lung transplant recipients in different chronic lung allograft dysfunction (CLAD) stages and longitudinal gut microbiome changes after transplantation. We found 108 species (58.1%) in end-stage lung disease patients and 139 species (74.7%) in lung transplant recipients that were differentially abundant compared with healthy controls, with several species exhibiting sharp longitudinal increases from before to after transplantation. Different combinations of immunosuppressants and antibiotics were associated with specific gut microbial signatures. We found that the gut microbiome of lung transplant recipients in CLAD stage 0 was more similar to healthy controls compared to those in CLAD stage 1. Finally, the gut microbial diversity of lung transplant recipients remained lower than the average gut microbial diversity of healthy controls up to more than 20 years post-transplantation. Gut dysbiosis, already present before lung transplantation was exacerbated following lung transplantation.