Browsing by Subject "INTESTINAL INFLAMMATION"

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  • Nieminen, Janne K.; Niemi, Mirja; Sipponen, Taina; Salo, Harri M.; Klemetti, Paula; Färkkilä, Martti Antero; Vakkila, Jukka; Vaarala, Outi (2013)
  • Aalto, Kristiina; Lahdenne, Pekka; Kolho, Kaija-Leena (2017)
    Background: Patients with juvenile idiopathic arthritis (JIA) on non-steroidal anti- inflammatory drugs (NSAIDs) may experience abdominal pain. In adults, NSAID use has been linked to an increase in fecal calprotectin (FC) levels, a surrogate marker for gut inflammation. In JIA, data on gut inflammation related to drug use is scarce. Methods: JIA patients followed up at the outpatient pediatric rheumatology clinic in Children's Hospital, Helsinki University Hospital, Helsinki, Finland were routinely assessed for FC if they complained about abdominal pain, had an elevated erythrocyte sedimentation rate (ESR) or used NSAIDs on a daily basis. The FC levels were related to the presence of abdominal pain, to ESR, and to the presence of HLA-B27. Results: Of the total group of 90 patients (median age 9.1 years; 45 JIA patients with disease modifying antirheumatic drugs (DMARDs), 25 without DMARD medication, and 20 arthralgia patients as controls), approximately 50% used NSAIDs, of whom 40% complained about abdominal pain. In patients with abdominal pain, one-third had elevated FC values (>100 mu g/g). The FC values, for the most part, declined along with the discontinuation or reduction of NSAIDs and after intensifying the DMARD medication, where after the pain disappeared. In patients with an elevated ESR, the FC values and ESR normalized in parallel. The presence of HLA-B27 was not associated with FC levels. Conclusion: In patients with JIA and abdominal pain, it may be useful to determine the FC when evaluating the need for further gastrointestinal examinations.
  • Rajamäki, Kristiina; Taira, Aurora; Katainen, Riku; Välimäki, Niko; Kuosmanen, Anna; Plaketti, Roosa-Maria; Seppälä, Toni T.; Ahtiainen, Maarit; Wirta, Erkki-Ville; Vartiainen, Emilia; Sulo, Päivi; Ravantti, Janne; Lehtipuro, Suvi; Granberg, Kirsi J.; Nykter, Matti; Tanskanen, Tomas; Ristimäki, Ari; Koskensalo, Selja; Renkonen-Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Taipale, Jussi; Mecklin, Jukka-Pekka; Aavikko, Mervi; Palin, Kimmo; Aaltonen, Lauri A. (2021)
    Background & Aims Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder associated with an elevated risk of colorectal cancer (CRC). IBD-associated CRC (IBD-CRC) may represent a distinct pathway of tumorigenesis compared to sporadic CRC (sCRC). Our aim was to comprehensively characterize IBD-associated tumorigenesis integrating multiple high-throughput approaches, and to compare the results with in-house data sets from sCRCs. Methods Whole-genome sequencing, single nucleotide polymorphism arrays, RNA sequencing, genome-wide methylation analysis, and immunohistochemistry were performed using fresh-frozen and formalin-fixed tissue samples of tumor and corresponding normal tissues from 31 patients with IBD-CRC. Results Transcriptome-based tumor subtyping revealed the complete absence of canonical epithelial tumor subtype associated with WNT signaling in IBD-CRCs, dominated instead by mesenchymal stroma-rich subtype. Negative WNT regulators AXIN2 and RNF43 were strongly down-regulated in IBD-CRCs and chromosomal gains at HNF4A, a negative regulator of WNT-induced epithelial–mesenchymal transition (EMT), were less frequent compared to sCRCs. Enrichment of hypomethylation at HNF4α binding sites was detected solely in sCRC genomes. PIGR and OSMR involved in mucosal immunity were dysregulated via epigenetic modifications in IBD-CRCs. Genome-wide analysis showed significant enrichment of noncoding mutations to 5′untranslated region of TP53 in IBD-CRCs. As reported previously, somatic mutations in APC and KRAS were less frequent in IBD-CRCs compared to sCRCs. Conclusions Distinct mechanisms of WNT pathway dysregulation skew IBD-CRCs toward mesenchymal tumor subtype, which may affect prognosis and treatment options. Increased OSMR signaling may favor the establishment of mesenchymal tumors in patients with IBD.
  • Cani, Patrice D.; de Vos, Willem M. (2017)
    Metabolic disorders associated with obesity and cardiometabolic disorders are worldwide epidemic. Among the different environmental factors, the gut microbiota is now considered as a key player interfering with energy metabolism and host susceptibility to several non-communicable diseases. Among the next-generation beneficial microbes that have been identified, Akkermansia muciniphila is a promising candidate. Indeed, A. muciniphila is inversely associated with obesity, diabetes, cardiometabolic diseases and low-grade inflammation. Besides the numerous correlations observed, a large body of evidence has demonstrated the causal beneficial impact of this bacterium in a variety of preclinical models. Translating these exciting observations to human would be the next logic step and it now appears that several obstacles that would prevent the use of A. muciniphila administration in humans have been overcome. Moreover, several lines of evidence indicate that pasteurization of A. muciniphila not only increases its stability but more importantly increases its efficacy. This strongly positions A. muciniphila in the forefront of next-generation candidates for developing novel food or pharma supplements with beneficial effects. Finally, a specific protein present on the outer membrane of A. muciniphila, termed Amuc_1100, could be strong candidate for future drug development. In conclusion, as plants and its related knowledge, known as pharmacognosy, have been the source for designing drugs over the last century, we propose that microbes and microbiomegnosy, or knowledge of our gut microbiome, can become a novel source of future therapies.
  • Af Björkesten, C. -G.; Jussila, A.; Kemppainen, H.; Hallinen, T.; Soini, E.; Mankinen, P.; Valgardsson, S.; Veckman, V.; Nissinen, R.; Naessens, D.; Molander, P. (2019)
    Background and Aims: A retrospective non-interventional, multi-centre patient chart review study was conducted to investigate the association of faecal calprotectin (FC) 1 year (+/- 2 months) after biological therapy initiation with composite event-free survival (CEFS) consisting of surgical procedures, corticosteroid initiation, treatment failure or dose increase in patients with Crohn's disease (CD). In addition, the correlations of FC and other tests of disease activity were assessed. Materials and methods: Data on Finnish CD patients initiating a biological therapy between 2010 and 2016, were collected. The association of FC and CEFS was analysed with Kaplan-Meier and Cox proportional hazard modelling. The correlations were tested with Pearson's test. Results: Biological therapy was initiated in 186 patients, of which 87 (46.8%) had FC results available at 1 year and 80 had follow-up exceeding 14 months. The characteristics of patients with and without FC results were similar. Patients with elevated FC (>250 mu g/g) had a significantly increased risk of experiencing composite event (HR 3.4, 95% CI: 1.3-8.9; p = .013) when compared to patients with normal FC (FC
  • Huang, Xin; Schuppan, Detlef; Tovar, Luis E. Rojas; Zevallos, Victor F.; Loponen, Jussi; Ganzle, Michael (2020)
    The ingestion of gluten-containing foods can cause wheat-related disorders in up to 15% of wheat consuming populations. Besides the role of gluten, alpha-amylase/trypsin inhibitors (ATI) have recently been identified as inducers of an innate immune response via toll-like receptor 4 in celiac disease and non-celiac wheat sensitivity. ATI are involved in plant self-defense against insects and possibly in grain development. Notably, they are largely resistant to gastrointestinal proteases and heat, and their inflammatory activity affects not only the intestine, but also peripheral organs. The aim of this study was to understand the changes of ATI throughout the sourdough and yeast-fermented bread-making processes. ATI tetramers were isolated, fluorescein-labelled, and added to a mini-dough bread-making system. When the pH decreased below 4.0 in sourdough fermentation, the ATI tetramers were degraded due to the activation of aspartic proteases, whilst in yeast fermentation, ATI tetramers remained intact. The amylase inhibitory activity after sourdough fermentation decreased significantly, while the concentration of free thiol groups increased. The glutathione reductase activity ofFructilactobacillus sanfranciscensisdid not contribute to the reduction of ATI tetramers. Compared to the unfermented wheat, sourdough fermentation was able to decrease the release of pro-inflammatory cytokines monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor alpha (TNF-alpha) in quantitative ATI extracts added to the human monocytic cell line THP-1. The current data suggest that sourdough fermentation can degrade ATI structure and bioactivity, and point to strategies to improve product development for wheat sensitivity patients.
  • Orlando, Giulia; Law, Philip J.; Palin, Kimmo; Tuupanen, Sari; Gylfe, Alexandra; Hanninen, Ulrika A.; Cajuso, Tatiana; Tanskanen, Tomas; Kondelin, Johanna; Kaasinen, Eevi; Sarin, Antti-Pekka; Kaprio, Jaakko; Eriksson, Johan G.; Rissanen, Harri; Knekt, Paul; Pukkala, Eero; Jousilahti, Pekka; Salomaa, Veikko; Ripatti, Samuli; Palotie, Aarno; Järvinen, Heikki; Renkonen-Sinisalo, Laura; Lepisto, Anna; Bohm, Jan; Mecklin, Jukka-Pekka; Al-Tassan, Nada A.; Palles, Claire; Martin, Lynn; Barclay, Ella; Tenesa, Albert; Farrington, Susan; Timofeeva, Maria N.; Meyer, Brian F.; Wakil, Salma M.; Campbell, Harry; Smith, Christopher G.; Idziaszczyk, Shelley; Maughan, Timothy S.; Kaplan, Richard; Kerr, Rachel; Kerr, David; Buchanan, Daniel D.; Win, Aung Ko; Hopper, John; Jenkins, Mark; Lindor, Noralane M.; Newcomb, Polly A.; Gallinger, Steve; Conti, David; Schumacher, Fred; Casey, Graham; Taipale, Jussi; Cheadle, Jeremy P.; Dunlop, Malcolm G.; Tomlinson, Ian P.; Aaltonen, Lauri A.; Houlston, Richard S. (2016)
    To identify new risk loci for colorectal cancer (CRC), we conducted a meta-analysis of seven genome-wide association studies (GWAS) with independent replication, totalling 13 656 CRC cases and 21 667 controls of European ancestry. The combined analysis identified a new risk association for CRC at 2q35 marked by rs992157 (P = 3.15 x 10(-8), odds ratio = 1.10, 95% confidence interval = 1.06-1.13), which is intronic to PNKD (paroxysmal non-kinesigenic dyskinesia) and TMBIM1 (transmembrane BAX inhibitor motif containing 1). Intriguingly this susceptibility single-nucleotide polymorphism (SNP) is in strong linkage disequilibrium (r(2) = 0.90, D' = 0.96) with the previously discovered GWAS SNP rs2382817 for inflammatory bowel disease (IBD). Following on from this observation we examined for pleiotropy, or shared genetic susceptibility, between CRC and the 200 established IBD risk loci, identifying an additional 11 significant associations (false discovery rate [FDR]) <0.05). Our findings provide further insight into the biological basis of inherited genetic susceptibility to CRC, and identify risk factors that may influence the development of both CRC and IBD.
  • Geisslitz, Sabrina; Shewry, Peter; Brouns, Fred; America, Antoine H. P.; Caio, Giacomo Pietro Ismaele; Daly, Matthew; D'Amico, Stefano; De Giorgio, Roberto; Gilissen, Luud; Grausgruber, Heinrich; Huang, Xin; Jonkers, Daisy; Keszthelyi, Daniel; Larre, Colette; Masci, Stefania; Mills, Clare; Moller, Marie Sofie; Sorrells, Mark E.; Svensson, Birte; Zevallos, Victor F.; Weegels, Peter Louis (2021)
    Amylase/trypsin-inhibitors (ATIs) comprise about 2-4% of the total wheat grain proteins and may contribute to natural defense against pests and pathogens. However, they are currently among the most widely studied wheat components because of their proposed role in adverse reactions to wheat consumption in humans. ATIs have long been known to contribute to IgE-mediated allergy (notably Bakers' asthma), but interest has increased since 2012 when they were shown to be able to trigger the innate immune system, with attention focused on their role in coeliac disease which affects about 1% of the population and, more recently, in non-coeliac wheat sensitivity which may affect up to 10% of the population. This has led to studies of their structure, inhibitory properties, genetics, control of expression, behavior during processing, effects on human adverse reactions to wheat and, most recently, strategies to modify their expression in the plant using gene editing. We therefore present an integrated account of this range of research, identifying inconsistencies, and gaps in our knowledge and identifying future research needs. Note This paper is the outcome of an invited international ATI expert meeting held in Amsterdam, February 3-5 2020