Publications by authors named "Danica Bajic"

4 Publications

  • Page 1 of 1

2'FL and LNnT Exert Antipathogenic Effects against ATCC 9689 In Vitro, Coinciding with Increased Levels of and/or Secondary Bile Acids.

Pathogens 2021 Jul 22;10(8). Epub 2021 Jul 22.

Glycom A/S-DSM Nutritional Products Ltd., Kogle Allé 4, DK-2970 Hørsholm, Denmark.

(formerly ) infection (CDI) is one of the most common hospital-acquired infections, which is often triggered by a dysbiosed indigenous gut microbiota (e.g., upon antibiotic therapy). Symptoms can be as severe as life-threatening colitis. The current study assessed the antipathogenic potential of human milk oligosaccharides (HMOs), i.e., 2'-O-fucosyllactose (2'FL), lacto-N-neotetraose (LNnT), and a combination thereof (MIX), against ATCC 9689 using in vitro gut models that allowed the evaluation of both direct and, upon microbiota modulation, indirect effects. During a first 48 h fecal batch study, dysbiosis and CDI were induced by dilution of the fecal inoculum. For each of the three donors tested, levels strongly decreased (with >4 log CFU/mL) upon treatment with 2'FL, LNnT and MIX versus untreated blanks, coinciding with increased acetate/ levels. Interindividual differences among donors at an intermediate time point suggested that the antimicrobial effect was microbiota-mediated rather than being a direct effect of the HMOs. During a subsequent 11 week study with the Pathogut model (specific application of the Simulator of the Human Intestinal Microbial Ecosystem (SHIME)), dysbiosis and CDI were induced by clindamycin (CLI) treatment. Vancomycin (VNC) treatment cured CDI, but the further dysbiosis of the indigenous microbiota likely contributed to CDI recurrence. Upon co-supplementation with VNC, both 2'FL and MIX boosted microbial activity (acetate and to lesser extent propionate/butyrate). Moreover, 2'FL avoided CDI recurrence, potentially because of increased secondary bile acid production. Overall, while not elucidating the exact antipathogenic mechanisms-of-action, the current study highlights the potential of HMOs to combat CDI recurrence, help the gut microbial community recover after antibiotic treatment, and hence counteract the adverse effects of antibiotic therapies.
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http://dx.doi.org/10.3390/pathogens10080927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402123PMC
July 2021

Phytochemical Characterization and Screening of Antioxidant, Antimicrobial and Antiproliferative Properties of Clementi and Two Varieties of L. Peel Extracts.

Plants (Basel) 2021 Apr 21;10(5). Epub 2021 Apr 21.

Department of Biology, Faculty of Science, University of Split, R. Boškovića 33, 21000 Split, Croatia.

Onions are one of the most widely grown vegetable crops. As production increases, so does the generation of waste from various parts of the onion, raising the need for efficient ecological disposal and use of such waste products. However, onion waste products are a rich source of antioxidants with a range of biological properties, therefore, they could potentially be used in food and pharmaceutical industries. In the present study, we identified the main flavonols and anthocyanins in peel extracts of Clement ex Visiani, 1842, and two varieties of L. and tested their antioxidant, antimicrobial and antiproliferative properties. Quercetin 3,4'-diglucolside, quercetin 4'-monoglucoside and quercetin are the most abundant flavonols in all onion extracts detected by high-performance liquid chromatography (HPLC) method. The composition of anthocyanins varied in all extracts. 2,2'-diphenyl-1-picrylhydrazyl (DPPH) and oxygen radical absorbance capacity (ORAC) assays showed that the triploid onion had the highest antioxidant power. Evaluation of antimicrobial activity by broth microdilution assay also showed that had higher antimicrobial activity compared to the red and yellow onion varieties. Comparable antiproliferative activity was confirmed for all onion extracts tested on three cancer cell lines: Hela (cervical cancer cell line), HCT116 (human colon cancer cell line) and U2OS (human osteosarcoma cell line). The most abundant onion flavonols (quercetin 3,4'-diglucoside and quercetin 4'-monoglucoside) showed weaker antimicrobial as well as antiproliferative properties compared to the extracts, leading to the conclusion that other phytochemicals besides flavonols contribute to the biological activity of onion peel extracts. The results demonstrate the antioxidant and antimicrobial properties of onion peels, which have promising potential as cancer cell proliferation inhibitors.
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http://dx.doi.org/10.3390/plants10050832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143352PMC
April 2021

Gut Microbiota-Derived Propionate Regulates the Expression of Reg3 Mucosal Lectins and Ameliorates Experimental Colitis in Mice.

J Crohns Colitis 2020 Oct;14(10):1462-1472

Klinik für Innere Medizin II, Klinikum rechts der Isar, Techn. Univ. Munich, Munich, Germany.

Background And Aims: Regenerating islet-derived protein type 3 [Reg3] lectins are antimicrobial peptides at mucosal surfaces of the gut, whose expression is regulated by pathogenic gut microbes via interleukin-22- or Toll-like receptor signalling. In addition to antimicrobial effects, tissue protection is hypothesized, but has been poorly investigated in the gut.

Methods: We applied antibiotic-induced microbiota perturbations, gnotobiotic approaches and a dextran-sodium sulfate [DSS] colitis model to assess microbial Reg3 regulation in the intestines and its role in colitis. We also used an intestinal organoid model to investigate this axis in vitro.

Results: First, we studied whether gut commensals are involved in Reg3 expression in mice, and found that antibiotic-mediated reduction of Clostridia downregulated intestinal Reg3B. A loss in Clostridia was accompanied by a significant reduction of short-chain fatty acids [SCFAs], and knock-out [KO] mice for SCFA receptors GPR43 and GPR109 expressed less intestinal Reg3B/-G. Propionate was found to induce Reg3 in intestinal organoids and in gnotobiotic mice colonized with a defined, SCFA-producing microbiota. Investigating the role of Reg3B as a protective factor in colitis, we found that Reg3B-KO mice display increased inflammation and less crypt proliferation in the DSS colitis model. Propionate decreased colitis and increased proliferation. Treatment of organoids exposed to DSS with Reg3B or propionate reversed the chemical injury with a loss of expression of the stem-cell marker Lgr5 and Olfm4.

Conclusions: Our results suggest that Clostridia can regulate Reg3-associated epithelial homeostasis through propionate signalling. We also provide evidence that the Reg3-propionate axis may be an important mediator of gut epithelial regeneration in colitis.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa065DOI Listing
October 2020

Cannabinoid Receptor Type 1 in the Brain Regulates the Affective Component of Visceral Pain in Mice.

Neuroscience 2018 08 7;384:397-405. Epub 2018 Jun 7.

Klinik und Poliklinik fuer Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. Electronic address:

Endocannabinoids acting through cannabinoid receptor type 1 (CB1) are major modulators of peripheral somatic and visceral nociception. Although only partially studied, some evidence suggests a particular role of CB1 within the brain in nociceptive processes. As the endocannabinoid system regulates affect and emotional behaviors, we hypothesized that cerebral CB1 influences affective processing of visceral pain-related behaviors in laboratory animals. To study nocifensive responses modulated by supraspinal CB1, we used conditional knock-out mice lacking CB1 either in cortical glutamatergic neurons (Glu-CB1-KO), or in forebrain GABAergic neurons (GABA-CB1-KO), or in principal neurons of the forebrain (CaMK-CB1-KO). These mutant mice and mice treated with the CB1 antagonist SR141716 were tested for different pain-related behaviors. In an acetic acid-induced abdominal constriction test, supraspinal CB1 deletions did not affect nocifensive responses. In the cerulein-model of acute pancreatitis, mechanical allodynia or hyperalgesia were not changed, but Glu-CB1- and CaMK-CB1-KO mice showed significantly increased facial grimacing scores indicating increased affective responses to this noxious visceral stimulus. Similarly, these brain-specific CB1 KO mice also showed significantly changed thermal nociception in a hot-plate test. These results reveal a novel, and important role of CB1 expressed by cortical glutamatergic neurons in the affective component of visceral nociception.
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http://dx.doi.org/10.1016/j.neuroscience.2018.05.041DOI Listing
August 2018
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