Browsing by Subject "COLITIS"

Sort by: Order: Results:

Now showing items 1-5 of 5
  • van der Lugt, Benthe; van Beek, Adriaan A.; Aalvink, Steven; Meijer, Ben; Sovran, Bruno; Vermeij, Wilbert P.; Brandt, Renata M. C.; de Vos, Willem M.; Savelkoul, Huub F. J.; Steegenga, Wilma T.; Belzer, Clara (2019)
    BackgroundThe use of Akkermansia muciniphila as potential therapeutic intervention is receiving increasing attention. Health benefits attributed to this bacterium include an improvement of metabolic disorders and exerting anti-inflammatory effects. The abundance of A. muciniphila is associated with a healthy gut in early mid- and later life. However, the effects of A. muciniphila on a decline in intestinal health during the aging process are not investigated yet. We supplemented accelerated aging Ercc1(-/7) mice with A. muciniphila for 10weeks and investigated histological, transcriptional and immunological aspects of intestinal health.ResultsThe thickness of the colonic mucus layer increased about 3-fold after long-term A. muciniphila supplementation and was even significantly thicker compared to mice supplemented with Lactobacillus plantarum WCFS1. Colonic gene expression profiles pointed towards a decreased expression of genes and pathways related to inflammation and immune function, and suggested a decreased presence of B cells in colon. Total B cell frequencies in spleen and mesenteric lymph nodes were not altered after A. muciniphila supplementation. Mature and immature B cell frequencies in bone marrow were increased, whereas B cell precursors were unaffected. These findings implicate that B cell migration rather than production was affected by A. muciniphila supplementation. Gene expression profiles in ileum pointed toward a decrease in metabolic- and immune-related processes and antimicrobial peptide production after A. muciniphila supplementation. Besides, A. muciniphila decreased the frequency of activated CD80(+)CD273(-) B cells in Peyer's patches. Additionally, the increased numbers of peritoneal resident macrophages and a decrease in Ly6C(int) monocyte frequencies in spleen and mesenteric lymph nodes add evidence for the potentially anti-inflammatory properties of A. muciniphila.ConclusionsAltogether, we show that supplementation with A. muciniphila prevented the age-related decline in thickness of the colonic mucus layer and attenuated inflammation and immune-related processes at old age. This study implies that A. muciniphila supplementation can contribute to a promotion of healthy aging.
  • Al-Samadi, Ahmed; Moossavi, Shirin; Salem, Abdelhakim; Sotoudeh, Masoud; Tuovinen, Sarianna M.; Konttinen, Yrjo T.; Salo, Tuula; Bishehsari, Faraz (2016)
    Colorectal cancer (CRC) is one of the most common cancers in both genders. Even though interleukin (IL)-17A was shown to play an important role in intestinal tumourigenesis and CRC, other IL-17 family members were not studied well. We therefore studied the expression of IL-17 cytokine family members in CRC. Ten healthy colons and ten CRC mucosa were immunostained for IL-17B, IL-17C, IL-17E, and IL-17F, and their receptors IL-17RA, IL-17RB, and IL-17RC. Double immunofluorescence staining of the CRC mucosa was done for IL-17B with markers of neutrophils, endothelial cells, macrophages, T cells, mast cells, or fibroblasts. While IL-17B was increased in CRC with a strong presence both in the epithelial and stromal compartments, IL-17C showed different expression depending on the grade of differentiation and IL-17E remained unchanged. In contrast, IL-17F was decreased in CRC compared to healthy control. Colon epithelial cells stained positive for IL-17RA, IL-17RB, and IL-17RC in both healthy control and CRC. Neutrophils were the main source of IL-17B in the stroma. IL-17 family members demonstrated distinct expression patterns in CRC, suggesting a differential role exerted by each member in colon carcinogenesis.
  • Hiippala, Kaisa; Kainulainen, Veera; Suutarinen, Maiju; Heini, Tuomas; Bowers, Jolene R.; Jasso-Selles, Daniel; Lemmer, Darrin; Valentine, Michael; Barnes, Riley; Engelthaler, David M.; Satokari, Reetta (2020)
    Altered intestinal microbiota is associated with systemic and intestinal diseases, such as inflammatory bowel disease (IBD). Dysbiotic microbiota with enhanced proinflammatory capacity is characterized by depletion of anaerobic commensals, increased proportion of facultatively anaerobic bacteria, as well as reduced diversity and stability. In this study, we developed a high-throughput in vitro screening assay to isolate intestinal commensal bacteria with anti-inflammatory capacity from a healthy fecal microbiota transplantation donor. Freshly isolated gut bacteria were screened for their capacity to attenuate Escherichia coli lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) release from HT-29 cells. The screen yielded a number of Bacteroides and Parabacteroides isolates, which were identified as P. distasonis, B. caccae, B. intestinalis, B. uniformis, B. fragilis, B. vulgatus and B. ovatus using whole genome sequencing. We observed that a cell-cell contact with the epithelium was not necessary to alleviate in vitro inflammation as spent culture media from the isolates were also effective and the anti-inflammatory action did not correlate with the enterocyte adherence capacity of the isolates. The anti-inflammatory isolates also exerted enterocyte monolayer reinforcing action and lacked essential genes to synthetize hexa-acylated, proinflammatory lipid A, part of LPS. Yet, the anti-inflammatory effector molecules remain to be identified. The Bacteroides strains isolated and characterized in this study have potential to be used as so-called next-generation probiotics.
  • Freitag, Tobias L.; Hartikainen, Anna; Jouhten, Hanne; Sahl, Cecilia; Meri, Seppo; Anttila, Veli-Jukka; Mattila, Eero; Arkkila, Perttu; Jalanka, Jonna; Satokari, Reetta (2019)
    Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI) and is also considered a potential treatment for a wide range of intestinal and systemic diseases. FMT corrects the microbial dysbiosis associated with rCDI, and the engraftment of donor microbiota is likely to play a key role in treatment efficacy. For disease indications other than rCDI, FMT treatment efficacy has been moderate. This may be partly due to stronger resilience of resident host microbiota in patients who do not suffer from rCDI. In rCDI, patients typically have undergone several antibiotic treatments prior to FMT, depleting the microbiota. In this study, we addressed the effect of broad-spectrum antibiotics (Ab) as a pre-treatment to FMT on the engraftment of donor microbiota in recipients. We conducted a pre-clinical study of FMT between two healthy mouse strains, Balb/c as donors and C57BL/6 as recipients, to perform FMT within the same species and to mimic interindividual FMT between human donors and patients. Microbiota composition was assessed with high-throughput 16S rDNA amplicon sequencing. The microbiota of Balb/c and C57BL/6 mice differed significantly, which allowed for the assessment of microbiota transplantation from the donor strain to the recipient. Our results showed that Ab-treatment depleted microbiota in C57BL/6 recipient mice prior to FMT. The diversity of microbiota did not recover spontaneously to baseline levels during 8 weeks after Ab-treatment, but was restored already at 2 weeks in mice receiving FMT. Interestingly, pre-treatment with antibiotics prior to FMT did not increase the overall similarity of the recipient's microbiota to that of the donor's, as compared with mice receiving FMT without Ab-treatment. Pre-treatment with Ab improved the establishment of only a few donor-derived taxa, such as Bifidobacterium, in the recipients, thus having a minor effect on the engraftment of donor microbiota in FMT. In conclusion, pre-treatment with broad-spectrum antibiotics did not improve the overall engraftment of donor microbiota, but did improve the engraftment of specific taxa. These results may inform future therapeutic studies of FMT.
  • Aaltonen, Gisele; Carpelan-Holmström, Monika; Keränen, Ilona; Lepistö, Anna (2018)
    To compare recurrence frequency and location between different types of bowel resections in Crohn's disease patients. This was a retrospective study of consecutive patients undergoing bowel resection for Crohn's disease between 2006 and 2016. Type of primary operation was recorded and grouped as ileocolic resection, small bowel resection, segmental colon resection with colocolic anastomosis or colorectal anastomosis, colectomy with ileorectal anastomosis, or end stoma operation. Binary logistic regression was used to compare surgical recurrence frequency between groups. We also investigated how Crohn's disease location at reoperations was related to the primary bowel resection type. Altogether, 218 patients with a median follow-up of 4.7 years were included in our study. Reoperation was performed in 42 (19.3%) patients. The risk of reoperation using the ileocolic resection group as reference was the following: small bowel resection (odds ratio (OR) 2.95, 95% confidence interval (CI) 1.01-8.66; P = 0.049), segmental colon resection with colocolic or colorectal anastomosis (OR 6.20, 95% CI 2.04-18.87; P = 0.001), colectomy with ileorectal anastomosis (OR 26.57, 95% CI 2.59-273.01; P = 0.006), and end stoma operation (OR 4.62, 95% CI 1.90-11.26; P = 0.001). In case of surgical recurrence, the reoperation type and location correlated with the primary bowel resection type. Reoperation frequency in Crohn's disease is lower after ileocolic resection than after other types of bowel resections. Surgical recurrence in Crohn's disease tends to maintain the disease location of the primary operation. One third of Crohn's patients undergoing an end stoma operation will still need new bowel resections due to recurrence.