Commensal Bacteria Derived Metabolite Butyrate Restores the Epithelial Mitochondrial Network Disrupted by the Crohn's Disease‐Associated Pathobiont Adherent Invasive <i>E‐coli</i> Infection
Bibliographic record
Abstract
Background Mitochondrial dysfunction has been implicated in several autoimmune and inflammatory diseases. Adherent‐invasive E. coli (AIEC) is a Crohn's disease‐associated pathobiont that triggers pro‐inflammatory responses. Previous work done by our group showed that AIEC (strain LF82) infection in gut epithelial cells (T84 human cell line) induces excessive mitochondrial network fragmentation with loss of mitochondrial membrane potential. Commensal bacteria in the gut produce useful metabolites such as short chain fatty acids (SCFA), which have a wide range of benefits including enhancing mitochondrial biogenesis. Aims (1) Determine the ability of sodium butyrate (Na‐But) treatment to restore mitochondrial functions disrupted by AIEC (strain LF82) infection in T84 epithelial cells. (2) Identify the mechanism utilized by Na‐But to impose its protective effect. Methods Mitochondrial network morphology was assessed via confocal microscopy live cell imaging of Mito‐tracker‐stained T84 epithelial cells, and images analyzed using ImageJ. We assessed the effect of Na‐But (10mM) on the proliferation of bacteria and their invasion of T84‐epithelia by growth curve analysis and gentamycin internalization assays. Mitochondrial membrane potential was measured by flow cytometry, and mRNA and protein expression of peroxisome proliferating activator receptor assessed by qPCR and immunoblotting. Results We confirmed that AIEC‐infection (strain LF82, 10 8 cfu, 4h) induces massive mitochondrial fragmentation in T84 cells (2x10 5 ). Co‐treatment with Na‐But and LF82 showed increased percentage of fused T84‐cell mitochondrial networks compared to LF82‐treated cells (Na‐But also reduced epithelial mitochondrial fragmentation caused by dinitrophenol (0.1mM, 2h)). The protective effect of Na‐But (3‐20mM; 0‐24hr) was neither due to inhibition of bacterial proliferation nor their invasion of the epithelia. Epithelia infected with E. coli ‐LF82 displayed reductions in mitochondrial membrane potential and mRNA expression of the master regulator of mitochondrial biogenesis, PGC1α: both effects were partially prevented by Na‐But. Conclusions These data indicate that pathogen disruption of the epithelial mitochondrial network is a component of IBD that could identify novel targets to control enteric inflammation. These data underscore the complex bacterial‐epithelium interaction: commensal organisms may preserve the mitochondrial network in the face of challenge from pathogens that seek to disrupt mitochondrial form and function.
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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) | 0.001 | 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".