A dietary fiber limits autoimmune neuroinflammation by restricting Th1 activation, polarization, and migration
Bibliographic record
Abstract
Abstract Dietary fibers and their breakdown products have been shown to limit inflammation in multiple disease contexts. However, the term “dietary fiber” encompasses a biochemically diverse family of carbohydrates, and it remains unknown how different fiber sources influence immune cell function. To address this question, we assessed the immunomodulatory capacity of different fiber types in a mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). C57BL/6 mice were fed a control diet (5% cellulose) or diets enriched (30%) with resistant starch, inulin, pectin, or guar gum for 2 weeks prior to EAE induction. A diet rich in guar gum uniquely ameliorated the clinical, pathological, and immunological features of EAE. Limited central nervous system (CNS) infiltration of IFNγ+ CD4+ T cells (Th1s) in guar gum-fed mice could be attributed to T cell-intrinsic impairment Th1 activation and polarization. Nanostring nCounter transcriptional analyses revealed downregulation of migration-associated markers in CD4+ T cells isolated from guar gum/EAE mice, which was supported by reduced cell-surface expression of integrins involved in migration into the CNS. Functionally, this translated to limited migration of guar gum-derived encephalitogenic Th1s into the CNS upon adoptive transfer into control-fed recipients, which reduced incidence and severity of EAE. However, the 16S rRNA microbiome signature and short chain fatty acid profiles were not unique in comparison to other fiber-supplemented diets, indicating a novel mechanism of action from those previously ascribed in high fiber diet studies. These data confirm the individuality of dietary fibers and identify a novel immunomodulatory function of guar gum. This project was supported by the endMS doctoral studentship program (Multiple Sclerosis Society of Canada) (NMF, JRA), the Canadian Institutes for Health Research (PJT-148909), and the Canada Research Chair program (LCO).
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".