A17 ROLE OF SEX-SPECIFIC GUT EPITHELIAL α2,6-SIALYLATED GALACTOSE IN COLONIC MUCUS FUNCTION, MICROBIAL ECOLOGY, AND PROTECTION FROM COLITIS.
Bibliographic record
Abstract
Abstract Background The heavily glycosylated Mucin-2 (MUC2) comprises gut mucus, which protects the colon from microbially-induced inflammation. Over 100 unique oligosaccharides (glycans) are found on MUC2, contributing to its barrier and microbiota-modulating functions. A major sugar on MUC2 glycans is sialic acid (Sia), which can occur via different stereoisomeric linkages, including an α2,6 linkage to galactose (Siaα2,6Gal). Siaα2,6Gal is a capping structure on mucus glycans that interacts with the microbiota. Synthesis of Siaα2,6Gal epitopes is mediated by beta-galactoside alpha-2,6-sialyltransferase 1 (ST6Gal1), and is implicated in sex-specific pathologies. However, its impact on gut mucus, microbiota, and colitis, along with the degree to which this is sex-specific, is unknown. Aims The aim of this study was to determine if the loss of gut epithelial Siaα2,6Gal has a sex-specific impact on gut mucus, microbiota and susceptiblity to colitis. Methods To address our aim, we generated mice conditionally deficient in ST6Gal1 in intestinal epithelial cells (IEC) using CreLox technology (IEC St6gal1-/- mice). We compared “floxed” male and female St6gal1f/f (wild-type, WT) and IEC St6gal1-/- littermates, focusing on mucus structure in situ, mucin glycomics via High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS), and microbiota composition through 16S rRNA profiling and metabolomic analysis. Clinical disease activity and histologic scores of colitis were assessed at baseline and following exposure to chemical (2.5% Dextran Sodium Sulfate, DSS) and microbial (Citrobacter rodentium) agents. Results Lectin staining confirmed a complete loss of Siaα2,6Gal in the colon crypts of IEC St6gal1-/- mice, validating the functionality of our model. At baseline, no major clinical symptoms or differences in mucus barrier integrity were observed between WT and IEC St6gal1-/- mice of either sex. However, sialomic and glycomic analyses revealed sex- and genotype-specific differences, with a notable impact on the relative mucin sulfation status in female IEC St6gal1-/- mice. Microbiota profiling highlighted an increased abundance of Bifidobacterium spp. in WT mice, a higher proportion of certain Firmicutes members in male IEC St6gal1-/- mice, and sex-specific differences in short-chain fatty acid production. DSS-induced colitis showed mildly worsened disease outcomes in male IEC St6gal1-/- mice, while acute bacterial-induced colitis caused by C. rodentium led to more severe large-intestinal inflammation in female IEC St6gal1-/- mice. Conclusions This work expands the current knowledge of the role of Siaα2,6Gal in vivo and its sex-specific impact on overall glycosylation, microbial ecology, and colitis susceptiblity. Funding Agencies CCC
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".