Objectives: Crohn’s disease is characterized by a gut dysbiosis with decreased abundance of butyrate producers such as Faecalibacterium prausnitzii. Although F. prausnitzii secretes anti-inflammatory molecules, few studies have addressed the importance of F. prausnitzii in a longitudinal setting. We aimed to examine the relationship between temporal profiles of F. prausnitzii, the C. leptum group, overall butyrate production, and inflammatory activity. Material and methods: Fecal samples (n = 59) were collected every third month from nine patients with ileal Crohn’s disease. The abundance of F. prausnitzii and C. leptum was quantified relative to the total amount of bacteria using quantitative-PCR. To assess butyrate production of gut microbiota, gene copy numbers of the butyryl-CoA:acetate-CoA transferase (BCoAT) gene were quantified by qPCR. The inflammatory activity was defined by fecal (f)-calprotectin. Results: No correlation between the relative abundance of F. prausnitzii, the C. leptum group, or copy numbers of the BCoAT gene, and f-calprotectin was observed in the total sample set. By analyzing alterations between consecutive samples, a negative correlation between changes in the relative abundance of F. prausnitzii and f-calprotectin was observed (R = −0.39; p = .009). Changes in C. leptum (R = −0.18, p = .23) and number of copies of the BCoAT gene (R = −0.12; p = .42) did not correlate with f-calprotectin. Conclusions: There was an inverse correlation between temporal changes in the relative abundance of F. prausnitzii, but not overall butyrate producing capacity, and changes in inflammatory activity in ileal Crohn’s disease. These findings indicate that F. prausnitzii may play a role in gut homeostasis, even though causality is still to be demonstrated.

Objective: Fecal microbiota transplantation (FMT) is a highly effective treatment forClostridioides difficileinfection (CDI). However, the fecal transplant’s causal components translating into clearance of the CDI are yet to be identified. The commensal bacteriaFaecalibacterium prausnitziimay be of great interest in this context, since it is one of the most common species of the healthy gut microbiota and produces metabolites with anti-inflammatory properties. Although there is mounting evidence thatF.prausnitziiis an important regulator of intestinal homeostasis, data about its role in CDI and FMT are relatively scarce.Methods: Stool samples from patients with recurrent CDI were collected to investigate the relative abundance ofF.prausnitziibefore and after FMT. Twenty-one patients provided fecal samples before the FMT procedure, at 2 weeks post-FMT, and at 2–4 months post-FMT. The relative abundance ofF.prausnitziiwas determined using quantitative polymerase chain reaction.Results: The abundance ofF.prausnitziiwas elevated in samples (N = 9) from donors compared to pre-FMT samples (N = 15) from patients (adjusted P<0.001). No significant difference in the abundance ofF.prausnitziibetween responders (N = 11) and non-responders (N = 4) was found before FMT (P = 0.85). In patients with CDI, the abundance ofF.prausnitziisignificantly increased in the 2 weeks post-FMT samples (N = 14) compared to the pre-FMT samples (N = 15, adjusted P<0.001). The increase persisted 2–4 months post-FMT (N = 15) compared to pre-FMT samples (N = 15) (adjusted P<0.001).Conclusions: FMT increases the relative abundance ofF.prausnitziiin patients with recurrent CDI, and this microbial shift remains several months later. The baseline abundance ofF.prausnitziiin donors or recipients was not associated with future treatment response, although a true predictive capacity cannot be excluded because of the limited sample size. Further studies are needed to discern whetherF.prausnitziiplays an active role in the resolution of CDI.

Background: Recent genetic and transcriptomic data highlight the need for improved molecular characterization of inflammatory bowel disease (IBD). Proteomics may advance the delineation of IBD phenotypes since it accounts for post-transcriptional modifications. Aims: We aimed to assess the IBD spectrum based on inflammatory serum proteins and identify discriminative patterns of underlying biological subtypes across multiple European cohorts. Methods: Using proximity extension methodology, we measured 86 inflammation-related serum proteins in 1551 IBD patients and 312 healthy controls (HC). We screened for proteins exhibiting significantly different levels among IBD subtypes and between IBD and HC. Classification models for differentiating between Crohn’s disease (CD) and ulcerative colitis (UC) were employed to explore the IBD spectrum based on estimated probability scores. Results: Levels of multiple proteins, such as interleukin-17A, matrix metalloproteinase-10, and fibroblast growth factor-19, differed (fold-change >1.2; false discovery rate 0.73) than colonic CD (median AUCs < 0.62). Models differentiating colonic CD from ileal CD demonstrated intermediate performance (median AUCs: 0.67–0.69). Conclusions: Our findings in serum proteins support the presence of a continuous IBD spectrum rather than a clear separation of CD and UC. Within the spectrum, disease location may reflect a more similar disease than CD versus UC, as colonic CD resembled UC more closely than ileal CD.

Background and Aims: The diagnostic and prognostic properties of anti-integrin αvβ6 immunoglobulin G (IgG) autoantibodies in ulcerative colitis (UC) are poorly understood. We aimed to assess the diagnostic performance of anti-integrin αvβ6 autoantibodies and examine their association with disease outcomes. Methods: Serum samples from a Swedish inception cohort of patients with suspected inflammatory bowel disease (IBD, n = 473) were analyzed using an in-house fluorescence enzyme immunoassay based on EliA technology. Findings were validated in a Norwegian population-based inception cohort (n = 570). Diagnostic performance was assessed by calculating the area under the curve (AUC) with 95% confidence intervals and determining sensitivity and specificity. Reclassification was evaluated using the net reclassification index. Results: In the discovery cohort, patients with UC, IBD-unclassified, or colonic Crohn’s disease exhibited higher median autoantibody levels compared to symptomatic and healthy controls. In the validation cohort, the autoantibody demonstrated 79% sensitivity and 94% specificity for UC vs symptomatic controls at a cut-off of 400 UA/l. Its diagnostic performance (AUC = 0.92, 95% CI, 0.89-0.95) was superior to hs-CRP (AUC = 0.65, 95% CI, 0.60-0.70, P < .001) and faecal calprotectin (fcalpro) (AUC = 0.88, 95% CI, 0.84-0.92, P = .09). Combining the autoantibody with fcalpro further improved diagnostic accuracy (AUC = 0.97, 95% CI, 0.95-0.98) and patient reclassification (P < .001). Autoantibody positivity was associated with a severe phenotype of UC, characterised by increased inflammatory activity and higher IL-17A and granzyme B levels. Higher autoantibody levels were linked to an aggressive disease course, remaining stable in aggressive UC but decreasing in indolent disease (P = .003). Conclusions: Anti-integrin αvβ6 is a reliable diagnostic and prognostic marker for UC, with potential clinical implementation.

Introduction: We aimed to determine the diagnostic and prognostic potential of baseline microbiome profiling in inflammatory bowel disease (IBD). Methods: Participants with ulcerative colitis (UC), Crohn’s disease (CD), suspected IBD, and non-IBD symptomatic controls were included in the prospective population-based cohort Inflammatory Bowel Disease in South-Eastern Norway III (third iteration) based on suspicion of IBD. The participants donated fecal samples that were analyzed with 16S rRNA sequencing. Disease course severity was evaluated at the 1-year follow-up. A stringent statistical consensus approach for differential abundance analysis with 3 different tools was applied, together with machine learning modeling. Results: A total of 1404 individuals were included, where n = 1229 samples from adults were used in the main analyses (n = 658 UC, n = 324 CD, n = 36 IBD-U, n = 67 suspected IBD, and n = 144 non-IBD symptomatic controls). Microbiome profiles were compared with biochemical markers in machine learning models to differentiate IBD from non-IBD symptomatic controls (area under the receiver operating curve [AUC] 0.75-0.79). For UC vs controls, integrating microbiome data with biochemical markers like fecal calprotectin mildly improved classification (AUC 0.83 to 0.86, P < .0001). Extensive differences in microbiome composition between UC and CD were identified, which could be quantified as an index of differentially abundant genera. This index was validated across published datasets from 3 continents. The UC-CD index discriminated between ileal and colonic CD (linear regression, P = .008) and between colonic CD and UC (P = .005), suggesting a location-dependent gradient. Microbiome profiles outperformed biochemical markers in predicting a severe disease course in UC (AUC 0.72 vs 0.65, P < .0001), even in those with a mild disease at baseline (AUC 0.66 vs 0.59, P < .0001). Conclusions: Fecal microbiome profiling at baseline held limited potential to diagnose IBD from non-IBD compared with standard-of-care. However, microbiome shows promise for predicting future disease courses in UC.

Proactive therapeutic drug monitoring (TDM) is often challenged by long turnaround time when using enzyme-linked immunosorbent assays (ELISAs), especially when analyses are centralised. Point-of-care tests (POCTs) allow rapid assessments, but data on their agreement with existing in-house methodologies are scarce. To examine the agreement between a POCT by ProciseDx (San Diego, CA) and the most frequently used in-house ELISA for infliximab (IFX) quantification in Sweden. Serum samples were analysed using the in-house ELISA, Karolinska University Hospital, Stockholm, Sweden and a POCT by ProciseDx (San Diego, CA). Agreement was assessed and differences were examined. Samples from 61 inflammatory bowel disease (IBD) patients were analysed with a median IFX concentration of 7.9 μg/mL (interquartile range (IQR) 5.5-13) for the POCT and 7.9 μg/mL (IQR 5.2-12) for the ELISA (Pearson's correlation coefficient = 0.95 (95% CI 0.92-0.97, p < .01)). A Passing-Bablok regression yielded an intercept of -0.44 and a slope of 1.09. The Bland-Altman plot showed a systemic bias of -0.77 μg/mL (95% CI -0.18 to -1.4) between the methods. The upper limit of agreement was 3.7 (95% CI 2.7-4.8) (μg/mL), whereas the lower limit agreement was -5.3 (95% CI -6.3 to -4.3) (μg/mL). An excellent reliability was observed, intraclass correlation showed = 0.94 (95% CI 0.89-0.96, p < .0001). When defining IFX concentration as subtherapeutic (7.0 μg/mL) drug levels, Kappa statistics showed a substantial agreement (0.79). The POCT by ProciseDx (San Diego, CA) demonstrated a good agreement with the in-house ELISA, supporting its use for rapid IFX quantification.