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Biomedicine & Pharmacotherapy =... Nov 2023Ulcerative colitis (UC) is a severe inflammatory bowel disease (IBD) characterized by multifactorial complex disorders triggered by environmental factors, genetic...
Faecalibacterium prausnitzii, Bacteroides faecis and Roseburia intestinalis attenuate clinical symptoms of experimental colitis by regulating Treg/Th17 cell balance and intestinal barrier integrity.
Ulcerative colitis (UC) is a severe inflammatory bowel disease (IBD) characterized by multifactorial complex disorders triggered by environmental factors, genetic susceptibility, and also gut microbial dysbiosis. Faecalibacterium prausnitzii, Bacteroides faecis, and Roseburia intestinalis are underrepresented species in UC patients, leading to the hypothesis that therapeutic application of those bacteria could ameliorate clinical symptoms and disease severity. Acute colitis was induced in mice by 3.5% DSS, and the commensal bacterial species were administered by oral gavage simultaneously with DSS treatment for up to 7 days. The signs of colonic inflammation, the intestinal barrier integrity, the proportion of regulatory T cells (Tregs), and the expression of pro-inflammatory and anti-inflammatory cytokines were quantified. The concentrations of SCFAs in feces were measured using Gas-liquid chromatography. The gut microbiome was analyzed in all treatment groups at the endpoint of the experiment. Results were benchmarked against a contemporary mesalazine treatment regime. We show that commensal species alone and in combination reduced disease activity index scores, inhibited colon shortening, strengthened the colonic epithelial barrier, and positively modulated tight junction protein expression. The expression level of pro-inflammatory cytokines was significantly reduced. Immune modulation occurred via inhibition of the loss of CD4 +CD25 +Treg cells in the spleen. Our study proofed that therapeutic application of F. prausnitzii, B. faecis, and R. intestinalis significantly ameliorated DSS-induced colitis at the level of clinical symptoms, histological inflammation, and immune status. Our data suggest that these positive effects are mediated by immune-modulatory pathways and influence on Treg/Th17 balance.
Topics: Humans; Mice; Animals; T-Lymphocytes, Regulatory; Faecalibacterium prausnitzii; Th17 Cells; Colitis; Colitis, Ulcerative; Colon; Cytokines; Bacteria; Inflammation; Dextran Sulfate; Disease Models, Animal; Mice, Inbred C57BL
PubMed: 37793274
DOI: 10.1016/j.biopha.2023.115568 -
Maedica Dec 2023Mesalazine is a drug used to treat ulcerative colitis and Crohn's disease, and is known to rarely cause lung injury. We show herein a unique case who developed this...
Mesalazine is a drug used to treat ulcerative colitis and Crohn's disease, and is known to rarely cause lung injury. We show herein a unique case who developed this drug-induced injury. A 17-year-old boy presented with fever and anorexia after administration of mesalazine. Computed tomography showed extensive ground-glass opacities with peripheral distribution in both lungs. He had general weakness, but had no respiratory symptoms such as cough and dyspnea. With prednisolone, which is primarily aimed at controlling ulcerative colitis, the extensive opacity in both lungs were improved. All patients with this drug-induced lung injury reported to date have had respiratory symptoms, but this patient had no subjective respiratory symptoms and had no abnormalities in respiratory rate and oxyhaemoglobin saturation. Although very rare, we do believe that this clinical course will provide some suggestive information on treatment for patients with similar course in the future.
PubMed: 38348085
DOI: 10.26574/maedica.2023.18.4.718 -
Therapeutische Umschau. Revue... Dec 2023Ulcerative colitis is characterized by a chronic intestinal inflammation limited to the mucosa of the colon, of variable proximal extent. Main symptoms are diarrhea,... (Review)
Review
Ulcerative colitis is characterized by a chronic intestinal inflammation limited to the mucosa of the colon, of variable proximal extent. Main symptoms are diarrhea, possibly bloody, and abdominal pain. It evolves with phases of relapse and remission. The diagnosis of ulcerative colitis is made based on clinical, endoscopic, and histologic findings. Currently, the various drug treatment options act by, among other things, reducing the activity of the immune system locally or systemically. In mild to moderate forms, 5-ASA remains the mainstay of both induction and maintenance treatment. In more severe flares, cortisone is the treatment of choice. To limit the prolonged/repeated intake of corticosteroids, there are several options of biologics with distinct ranges of action and safety profiles for inducing and/or maintaining remission. Therapeutic goals are evolving and go beyond achieving clinical remission. Endoscopic and histological remission are new targets to further improve quality of life and limit long-term complications, such as colorectal cancer.
Topics: Humans; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Inflammation; Mesalamine; Quality of Life
PubMed: 38095251
DOI: No ID Found -
Journal of the Canadian Association of... Feb 2024Those managing ulcerative colitis (UC) must be aware of new treatments. Mesalamine (5-ASA) is the first treatment for mild UC. Steroids have been the first therapy for...
Those managing ulcerative colitis (UC) must be aware of new treatments. Mesalamine (5-ASA) is the first treatment for mild UC. Steroids have been the first therapy for patients with more severe UC but these are not effective or safe long term. This means that other medicines are needed. Newer advanced therapies are now frequently used. There are several types of advanced therapies. These are the anti-TNF, anti-integrin and anti-IL12/23 agents as well as the JAK inhibitors and sphingosine1-phosphate receptor modulators. All of these are effective in treating UC. Choosing among treatments is complicated. There are multiple factors to think about when choosing a treatment for UC. Without research studies that directly compare the different treatments, the use of any one treatment should be based on effectiveness and safety. Other considerations include specific disease features, patient factors and the preference of patients.
PubMed: 38314181
DOI: 10.1093/jcag/gwad025 -
Lipids in Health and Disease Nov 2023Disturbed bile acid homeostasis associated with a rise of primary and a decline of secondary bile acids is a consistent finding in inflammatory bowel diseases (IBDs)....
BACKGROUND
Disturbed bile acid homeostasis associated with a rise of primary and a decline of secondary bile acids is a consistent finding in inflammatory bowel diseases (IBDs). Whether fecal bile acids may emerge as biomarkers for IBD diagnosis and disease severity is less clear. Our study aimed to identify associations of 18 fecal bile acid species with IBD entity and disease activity.
METHODS
Stool samples of 62 IBD patients and 17 controls were collected. Eighteen fecal bile acid species were quantified by LC-MS/MS using stable isotope dilution. Lipid levels normalized to a dry weight of the fecal homogenates and ratios of single bile acid species to total bile acid levels were used for calculations.
RESULTS
IBD patients exhibited altered primary and secondary bile acid ratios in stool, with notable distinctions between ulcerative colitis (UC) compared to Crohn's disease (CD) and healthy controls. Fecal calprotectin was negatively correlated with glycolithocholic acid (GLCA) and hyodeoxycholic acid (HDCA) in UC. These bile acids were reduced in stool of UC patients with fecal calprotectin levels > 500 µg/g compared to UC patients with low calprotectin levels. Moreover, negative associations of six secondary bile acids with C-reactive protein (CRP) existed in UC. In CD patients, fecal bile acids did not correlate with CRP or fecal calprotectin. Diarrhoea is common in IBD, and UC patients with diarrhoea had reduced deoxycholic acid (DCA), glycine conjugated DCA (GDCA) and lithocholic acid in stool in contrast to patients with normal stool consistency. Fecal bile acid levels were not associated with diarrhoea in CD patients. UC patients treated with mesalazine had increased levels of fecal GDCA whereas no such changes were observed in CD patients. Bile acid levels of CD and UC patients treated with biologicals or corticosteroids did not change. Relative levels of GHDCA (specificity: 79%, sensitivity: 67%) and glycochenodeoxycholic acid (specificity: 74%, sensitivity: 63%) were the most specific to distinguish UC from CD.
CONCLUSION
Disrupted fecal bile acid homeostasis is associated with disease severity and disease symptoms in UC but not in CD, potentially aiding in distinguishing IBD subtypes and classifying the pathophysiology of diarrhoea in UC.
Topics: Humans; Colitis, Ulcerative; Bile Acids and Salts; Chromatography, Liquid; Tandem Mass Spectrometry; Inflammatory Bowel Diseases; Crohn Disease; Biomarkers; C-Reactive Protein; Diarrhea; Feces; Leukocyte L1 Antigen Complex
PubMed: 37980492
DOI: 10.1186/s12944-023-01971-4 -
ACS Measurement Science Au Feb 2024Mesalamine, known as 5-aminosalicylic acid, is a medication used primarily in the treatment of inflammatory bowel disease, including ulcerative colitis and Crohn's... (Review)
Review
Mesalamine, known as 5-aminosalicylic acid, is a medication used primarily in the treatment of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. 5-Aminosalicylic acid can be measured using various benchtop laboratory techniques which involve liquid chromatography-mass spectroscopy, but these are sophisticated and large, meaning that they cannot be used on-site because transportation of the samples, chemicals, and physical and biological reactions can potentially occur, which can affect the sample's composition and potentially result in inaccurate results. An alternative approach is the use of electrochemical based sensing platforms which has the advantages of portability, cost-efficiency, facile miniaturization, and rapid analysis while nonetheless providing sensitivity and selectivity. We provide an overview of the use of the electroanalytical techniques for the sensing of 5-aminosalicylic acid and compare them to other laboratory-based measurements. The applications, challenges faced, and future opportunities for electroanalytical based sensing platforms are presented in this review.
PubMed: 38404492
DOI: 10.1021/acsmeasuresciau.3c00061 -
Disease-a-month : DM Nov 2023The prevalence and incidence of Ulcerative Colitis (UC), a recurrent and remitting inflammatory condition, are rising. Any part of the colon may be affected, beginning... (Review)
Review
The prevalence and incidence of Ulcerative Colitis (UC), a recurrent and remitting inflammatory condition, are rising. Any part of the colon may be affected, beginning with inflammation of the mucosa in the rectum and continuing proximally continuously. Bloody diarrhea, tenesmus, fecal urgency, and stomach pain are typical presenting symptoms. Many patients present with extraintestinal manifestations (EIMs) including musculoskeletal, ocular, renal, hepatobiliary, and dermatological presentation, among others. Most cases are treated with pharmacological therapy including mesalazine and glucocorticoids. Fecal microbiota transplantation (FMT) is a novel procedure that is increasingly being used to treat UC, however, its use yet remains controversial because of uncertain efficacy. FMT can lower gut permeability and consequently disease severity by boosting short-chain fatty acids production, helping in epithelial barrier integrity preservation. Upadacitinib (JAK Kinase inhibitor) is another newer treatment option, which is an FDA-approved drug that is being used to treat UC. This review article provides a comprehensive review of the EIMs of UC, the role of FMT along with various recent clinical trials pertaining to FMT as well as other diagnostic and therapeutic updates.
Topics: Humans; Colitis, Ulcerative; Fecal Microbiota Transplantation; Feces; Inflammation; Treatment Outcome
PubMed: 37357103
DOI: 10.1016/j.disamonth.2023.101606 -
Biomedicine & Pharmacotherapy =... Nov 2023Clostridioides difficile infection (CDI) induces intense acute inflammatory responses through toxin release. A combination of antibiotic and anti-inflammatory agents is...
BACKGROUND AND AIMS
Clostridioides difficile infection (CDI) induces intense acute inflammatory responses through toxin release. A combination of antibiotic and anti-inflammatory agents is sometimes recommended in severe, non-responsive cases, although clinical trials have been inconclusive, raising concerns about potential complications. This study aims to investigate the effect of budesonide and mesalamine in the treatment of CDI in a murine model, by evaluating the combination of fidaxomicin and these anti-inflammatory drugs.
METHOD
C57BL/6 J female mice pretreated with an antimicrobial mixture were challenged with C. difficile VPI 10463 or culture media by gavage. After the challenge, mice received placebo, fidaxomicin alone (20 mg/kg), or fidaxomicin combined with mesalamine (200, 400 mg/kg) or budesonide (0.2, 1, 10 mg/kg) for 5 days. The mice were monitored for 7 days with weight and survival. Colon and cecum tissues were harvested for histological assessment.
RESULTS
CDI of mice caused 80% mortality. Fidaxomicin completely protected against CDI in all parameters (weight, survival and pathscores). Mortality rates were up to 90%, 70% in budesonide(10 mg/kg) and mesalamine (400 mg/kg) treatment group, respectively. Budesonide (0.02,0.1 and 1 mg/kg) adjunction to fidaxomicin worsened the disease outcome according to all tested parameters. While mesalamine in combination with fidaxomicin (200, 400 mg/kg) did not lead to any deaths during CDI treatment, it did not provide additional benefits.
CONCLUSIONS
Anti-inflammatory drugs including corticosteroid therapy may worsen the incidence and severity of CDI in this mouse model. These studies may have important clinical implications for understanding the role of anti-inflammatory/ corticosteroid therapy in CDI and inflammatory bowel disease management.
PubMed: 37713991
DOI: 10.1016/j.biopha.2023.115489 -
The Medical Letter on Drugs and... Nov 2023
Topics: Humans; Colitis, Ulcerative; Acetates; Indoles
PubMed: 37983118
DOI: 10.58347/tml.2023.1690b -
The Medical Letter on Drugs and... Jul 2023
Topics: Humans; Inflammatory Bowel Diseases; Immunosuppressive Agents; Colitis, Ulcerative; Infliximab
PubMed: 37418329
DOI: 10.58347/tml.2023.1680a