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Growing evidence suggests that impaired gut permeability and gut microbiota alterations are involved in the pathogenesis of Inflammatory Bowel Diseases (IBDs), which include Ulcerative Colitis (UC) and Crohn's Disease (CD). Vedolizumab is an anti-α4β7 antibody approved for IBD treatment, used as the first treatment or second-line therapy when the first line results in inadequate effectiveness. The aim of this study is to develop a mathematical model capable of describing the pathophysiological mechanisms of Vedolizumab treatment in IBD patients. In particular, the relationship between drug concentration in the blood, colonic mucosal permeability and fecal microbiota composition was investigated and modeled to detect and predict trends in order to support and tailor Vedolizumab therapies. To pursue this aim, clinical data from a pilot study on a cluster of 11 IBD patients were analyzed. Enrolled patients underwent colonoscopy in three phases (before (t0), after 24 weeks of (t1) and after 52 weeks of (t2 ) Vedolizumab treatment) to collect mucosal biopsies for transepithelial electrical resistance (TEER) evaluation (permeability to ions), intestinal permeability measurement and histological analysis. Moreover, fecal samples were collected for the intestinal microbiota analysis at the three time points. The collected data were compared to those of 11 healthy subjects at t0, who underwent colonoscopy for screening surveillance, and used to implement a three-compartmental mathematical model (comprising central blood, peripheral blood and the intestine). The latter extends previous evidence from the literature, based on the regression of experimental data, to link drug concentration in the peripheral blood compartment with abundance and intestinal permeability. The clinical data showed that Vedolizumab treatment leads to an increase in TEER and a reduction in intestinal permeability to a paracellular probe, improving tissue inflammation status. Microbiota analysis showed increasing values of , albeit not statistically significant. This trend was adequately reproduced by the mathematical model, which offers a useful tool to describe the pathophysiological effects of Vedolizumab therapy on colonic mucosal permeability and fecal microbiota composition. The model's satisfactory predictive capabilities and simplicity shed light on the relationship between the drug, the microbiota and permeability and allow for its straightforward extension to diverse therapeutic conditions.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11274165 | PMC |
http://dx.doi.org/10.3390/bioengineering11070710 | DOI Listing |
Pharmacol Ther
December 2024
Institute of Microbiology and Molecular Genetics, University of the Punjab, New Campus, Lahore 54590, Pakistan. Electronic address:
Polycystic Ovarian Syndrome is one of the major prevalent causes of infertility reported worldwide nearly 6-26 %, especially in girls hitting puberty and women at their childbearing age. The main clinical manifestations include irregular menstrual cycle, small cysts on one or both ovaries, chronic oligo-anovulation, and hirsutism. The etiological criteria are very complex and related to many factors like obesity, insulin sensitivity, inflammation, hyperandrogenism, diabetes mellitus type II, cardiovascular diseases, and dysbiosis of gut microbiota.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.
Nephrotic syndrome (NS) represents a prevalent syndrome among various chronic kidney disease pathologies and is known for its higher severity and worse prognosis compared with chronic glomerulonephritis. Understanding its pathogenesis and identifying more effective treatment modalities have long been a concern of kidney specialists. With the introduction of the gut-kidney axis concept and the progress in omics technologies, alterations in the gut microbiota have been observed in primary and secondary NS.
View Article and Find Full Text PDFFront Pharmacol
December 2024
Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Hypertension is a common disease; however, it is more prevalent in older adults, and its prevalence is increasing in younger populations. Numerous studies have revealed that hypertension and the composition and functionality of the intestinal flora are closely correlated. The balance of the intestinal flora, intestinal barrier integrity, and metabolite content of the intestinal flora play significant roles in the occurrence and progression of hypertension.
View Article and Find Full Text PDFFood Funct
December 2024
College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Integrated Research Base of Southern Fruit and Vegetable Preservation Technology, Zhejiang International Scientific and Technological Cooperation Base of Health Food Manufacturing and Quality Control, Zhejiang University, Hangzhou 310058, China.
Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic conditions characterized by periods of intestinal inflammation and have become global diseases. Dietary pectins have shown protective effects on IBD models. However, the development of pectin-based diet intervention for IBD individuals requires knowledge of both the bioactive structural patterns and the mechanisms underlying diet-microbiota-host interactions.
View Article and Find Full Text PDFChin Med
December 2024
Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, China.
Background: Liuweizhiji Gegen-Sangshen oral liquid (LGS), as a Chinese medicinal preparation, is developed from a Traditional Chinese medicinal formula consisting of six Chinese medicinal herbs, including Puerariae lobatae radix, Hoveniae semen, Imperatae rhizoma, Crataegi fructus, Mori fructus and Canarli fructus, and has been extensively utilized in the prevention and treatment of alcoholic liver disease (ALD) clinically. Previous study has demonstrated that LGS dose-dependently mitigated ALD in rat models. However, whether and how the main characteristic constituents of LGS (the flavonoid and polysaccharide fractions, LGSF and LGSP) contribute to the anti-ALD effect remains unclear.
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