Abstract
Background and Aims
Endoscopy and the use of faecal calprotectin faecal CP are among the least-favoured methods for assessing disease activity by inflammatory bowel disease IBD patients; the ...handling/processing of faecal samples is also impractical. Therefore, we sought to develop a novel neo-epitope serum calprotectin enzyme-linked immunosorbent assay ELISA, CPa9-HNE, with the aim of quantifying neutrophil activity and neutrophil extracellular trap NET-osis and proposing a non-invasive method for monitoring disease activity in IBD patients.
Methods
In vitro cleavage was performed by mixing calprotectin S100A9/S100A8 with human neutrophil elastase HNE, and a novel HNE-derived calprotectin neo-epitope CPa9-HNE was identified by mass spectrometry for ELISA development. The CPa9-HNE ELISA was quantified in supernatants from ex vivo activated neutrophils and serum samples from patients with ulcerative colitis UC, n = 43, Crohn’s disease CD, n = 93, and healthy subjects HS, n = 23. For comparison, faecal CP and MRP8/14 biomarkers were also measured.
Results
CPa9-HNE was specific for activated neutrophils ex vivo. Serum CPa9-HNE levels were 4-fold higher in CD p <0.0001 and UC p <0.0001 patients than in HS. CPa9-HNE correlated well with the Simple Endoscopic Score SES-CD score r = 0.61, p <0.0001, MES r = 0.46, p = 0.0141, and the full Mayo score r = 0.52, p = 0.0013. CPa9-HNE was able to differentiate between CD and UC patients in endoscopic remission and moderate/severe disease activity (CD: area under the curve AUC = 0.82 p = 0.0003, UC: AUC = 0.87 p = 0.0004). The performance of CPa9-HNE was equipotent or slightly better than that of faecal CP.
Conclusions
Serum CPa9-HNE levels were highly associated with CD and UC patients. CPa9-HNE correlated with the SES-CD score and the full Mayo score, indicating a strong association with disease activity.
The healthy intestine represents a remarkable interface where sterile host tissues come in contact with gut microbiota, in a balanced state of homeostasis. The imbalance of gut homeostasis is ...associated with the onset of many severe pathological conditions, such as inflammatory bowel disease (IBD), a chronic gastrointestinal disorder increasing in incidence and severely influencing affected individuals. Despite the recent development of next generation sequencing and bioinformatics, the current scientific knowledge of specific triggers and diagnostic markers to improve interventional approaches in IBD is still scarce. In this review we present and discuss currently available and emerging therapeutic options in modulating composition and metabolic activity of gut microbiota in patients affected by IBD. Therapeutic approaches at the microbiota level, such as dietary interventions alone or with probiotics, prebiotics and synbiotics, administration of antibiotics, performing fecal microbiota transplantation (FMT) and the use of nematodes, all represent a promising opportunities towards establishing and maintaining of well-being as well as improving underlying IBD symptoms.
The knowledge on how gut microbes contribute to the inflammatory bowel disease (IBD) at the onset of disease is still scarce. We compared gut microbiota in newly diagnosed, treatment-naïve adult IBD ...(Crohn's disease (CD) and ulcerative colitis (UC)) to irritable bowel syndrome (IBS) patients and healthy group. Mucosal and fecal microbiota of 49 patients (13 UC, 10 CD, and 26 IBS) before treatment initiation, and fecal microbiota of 12 healthy subjects was characterized by 16S rRNA gene sequencing. Mucosa was sampled at six positions, from terminal ileum to rectum. We demonstrate that mucosal microbiota is spatially homogeneous, cannot be differentiated based on the local inflammation status and yet provides bacterial footprints superior to fecal in discriminating disease phenotypes. IBD groups showed decreased bacterial diversity in mucosa at all taxonomic levels compared to IBS. In CD and UC, Dialister was significantly increased, and expansion of Haemophilus and Propionibacterium characterized UC. Compared to healthy individuals, fecal microbiota of IBD and IBS patients had increased abundance of Proteobacteria, Enterobacteriaceae, in particular. Shift toward reduction of Adlercreutzia and butyrate-producing taxa was found in feces of IBD patients. Microbiota alterations detected in newly diagnosed treatment-naïve adult patients indicate that the microbiota changes are set and detectable at the disease onset and likely have a discerning role in IBD pathophysiology. Our results justify further investigation of the taxa discriminating between disease groups, such as H. parainfluenzae, R. gnavus, Turicibacteriaceae, Dialister, and Adlercreutzia as potential biomarkers of the disease.
sindrom (RFS) je ozbiljna i potencijalno fatalna komplikacija koja se javlja u bolesnika s ozbiljnom pothranjenosti različite etiologije nakon ponovnog, nekontroliranog uvođenja prehrane, osobito ...ugljikohidrata. Nastanak komplikacija RFS-a, koje mogu zahvatiti bilo koji organski sustav ili više njih uslijed ozbiljnog elektrolitskog disbalansa, uvjetovan je brzim metaboličkim promjenama koje nastaju prilikom prelaska organizma iz katabolizma u anabolizam te unutarstaničnom deplecijom fosfora, kalija, magnezija te vitamina i mineralnih tvari. Najčešće komplikacije RFS-a vezane uz nedostatak vitamina odnose se na nedostatak tiamina. Zbog svoje ključne koenzimske uloge u metabolizmu ugljikohidrata i aminokiselina razgranatih lanaca, tiamin je važan čimbenik za održavanje normalne funkcije prije svega cerebralnog metabolizma. Razumijevanje temeljnih biokemijskih procesa tijekom gladovanja te posljedično mehanizama i čimbenika koji utječu na metaboličke promjene tijekom RFS-a važno je radi pravovremenog prepoznavanja bolesnika u riziku i prevencije RFS-a te brojnih kliničkih komplikacija koje nosi bez obzira na modalitet nutritivne potpore.
Pandemija infekcije COVID-19 predstavlja neviđene izazove i prijetnje za pacijente i zdravstvene sustave u cijelome svijetu. Akutne respiratorne komplikacije koje zahtijevaju liječenje u jedinicama ...intenzivnog liječenja (JIL) glavni su uzrok pobola i smrtnosti kod pacijenata sa infekcijom COVID-19. Pacijenti s najlošijim ishodima i većom smrtnošću su imunokompromitirani bolesnici, posebice starije dobi te polimorbidni, kao i pothranjeni bolesnici. Trajanje boravka u JIL-u, polimorbiditet i starija dob obično su povezani s visokim rizikom pothranjenosti, što je samo po sebi relevantan čimbenik rizika za veći pobol i smrtnost u bolesnika s kroničnim i akutnim bolestima. Za bolesnike s infekcijom COVID-19 često je potreban produljeni boravak u JIL-u u svrhu stabilizacije, a to može izravno uzrokovati ili pogoršati malnutriciju, uz pridruženi gubitak skeletne mišićne mase i funkcije koji vode ka invaliditetu, smanjenoj kvaliteti života i dodatnom morbiditetu. Prevenciju, dijagnozu i liječenje malnutricije stoga treba rutinski uključiti u liječenje bolesnika s infekcijom COVID-19. U ovome dokumentu Europsko društvo za kliničku prehranu i metabolizam (ESPEN) ima za cilj pružiti sažete smjernice za nutritivnu potporu bolesnika s COVID-19 te predlaže 10 praktičnih preporuka. Praktične smjernice usmjerene su na bolesnike u JIL-u ili u slučaju starije dobi i polimorbiditeta, koji su neovisno povezani s malnutricijom i njezinim negativnim utjecajem na preživljavanje bolesnika.
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