Background: A widely used method in assessing small bowel permeability is the lactulose:mannitol test, where the lactulose:mannitol ratio (LMR) is measured. However, there is discrepancy in how the test is conducted and in the values of LMR obtained across studies. This meta-analysis aims to determine LMR in healthy subjects, coeliac and Crohn's disease.
Methods: A literature search was performed using PRISMA guidance to identify studies assessing LMR in coeliac or Crohn's disease. 19 studies included in the meta-analysis measured gut permeability in coeliac disease, 17 studies in Crohn's disease. Outcomes of interest were LMR values and comparisons of standard mean difference (SMD) and weighted mean difference (WMD) in healthy controls, inactive Crohn's, active Crohn's, treated coeliac and untreated coeliac. Pooled estimates of differences in LMR were calculated using the random effects model.
Results: Pooled LMR in healthy controls was 0.014 (95% CI: 0.006-0.022) while pooled LMRs in untreated and treated coeliac were 0.133 (95% CI: 0.089-0.178) and 0.037 (95% CI: 0.019-0.055). In active and inactive Crohn's disease, pooled LMRs were 0.093 (95% CI: 0.031-0.156) and 0.028 (95% CI: 0.015-0.041). Significant differences were observed in LMR between: (1) healthy controls and treated coeliacs (SMD = 0.409 95% CI 0.034 to 0.783, p = 0.032), (2) healthy controls and untreated coeliacs (SMD = 1.362 95% CI: 0.740 to 1.984, p < 0.001), (3) treated coeliacs and untreated coeliacs (SMD = 0.722 95% CI: 0.286 to 1.157, p = 0.001), (4) healthy controls and inactive Crohn's (SMD = 1.265 95% CI: 0.845 to 1.686, p < 0.001), (5) healthy controls and active Crohn's (SMD = 2.868 95% CI: 2.112 to 3.623, p < 0.001), and (6) active Crohn's and inactive Crohn's (SMD = 1.429 (95% CI: 0.580 to 2.278, p = 0.001). High heterogeneity was observed, which was attributed to variability in protocols used across different studies.
Conclusion: The use of gut permeability measurements in screening and monitoring of coeliac and Crohn's disease is promising. LMR is useful in performing this function with significant limitations. More robust alternative tests with higher degrees of clinical evidence are needed if measurements of gut permeability are to find widespread clinical use.
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http://dx.doi.org/10.1186/s12876-021-02082-z | DOI Listing |
Cell Chem Biol
December 2024
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address:
Chemical inducers of proximity (CIPs) are molecules that recruit one protein to another and introduce new functionalities toward modulating protein states and activities. While CIP-mediated recruitment of E3 ligases is widely exploited for the development of degraders, other therapeutic modalities remain underexplored. We describe a non-degrader CIP-DNA-encoded library (CIP-DEL) that recruits FKBP12 to target proteins using non-traditional acyclic structures, with an emphasis on introducing stereochemically diverse and rigid connectors to attach the combinatorial library.
View Article and Find Full Text PDFJ Surg Res
January 2025
Department of Pediatric Surgery, Massachusetts General Hospital, Boston, Massachusetts.
Introduction: Pediatric-onset Crohn's disease (CD) has a more severe phenotype than adult-onset, and nearly one-third of pediatric CD patients will require surgical therapy. There is limited data on patient/disease characteristics that are associated with earlier surgical management.
Methods: All pediatric CD patients (<22 yrs) who underwent ileocolectomy from 2005 to 2021 were included.
Kidney360
January 2025
Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Background: Epidemiological associations between kidney stone disease (KSD) and gastrointestinal disorders have been reported, and intestinal homeostasis plays a critical role in stone formation. However, the underlying intrinsic link is not adequately understood. This study aims to investigate the genetic associations between these two types of diseases.
View Article and Find Full Text PDFInt J Colorectal Dis
January 2025
Royal Brisbane and Women's Hospital, Butterfield St., Herston, QLD, 4006, Australia.
Purpose: Given the evolving literature regarding the optimal surgical approach to mitigate post-operative recurrence of Crohn's disease (CD), this survey study aimed to elucidate the practices and preferences of colorectal surgeons in Australia and New Zealand (ANZ) in their surgical management of CD.
Methods: Colorectal surgical consultants and fellows (n = 337) registered with the Colorectal Surgical Society of Australia and New Zealand (CSSANZ) were invited by email in April 2022 to participate in a cross-sectional survey consisting of basic demographics and 12 questions relating to their usual surgical practice and preferred operative strategy.
Results: A total of 135 responses were received (39.
Alzheimers Dement
December 2024
School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Background: An increasing body of evidence has suggested that the pathogenesis of Alzheimer's disease (AD) is not confined to the neurons but instead that neuroinflammation plays a significant role in the disease, with an interplay between the brain and the immune system. So far, their shared genetic components have not been systematically studied.
Method: We investigated the shared genetic architecture between AD and a plethora of immune-mediated diseases using the genome-wide association studies (GWAS) summary statistics data: allergic rhinitis, asthma, atopic dermatitis, celiac disease, Crohn's disease, hypothyroidism, primary sclerosing cholangitis, RA, systemic lupus erythematosus, ulcerative colitis, and vitiligo.
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