Synergistic Protection of Combined Probiotic Conditioned Media against Neonatal Necrotizing Enterocolitis-Like Intestinal Injury
Bibliographic record
Abstract
Balance among the complex interactions of the gut microbial community is important for intestinal health. Probiotic bacteria can improve bacterial balance and have been used to treat gastrointestinal diseases. Neonatal necrotizing enterocolitis (NEC) is a life-threatening inflammatory bowel disorder primarily affecting premature infants. NEC is associated with extensive inflammatory NF-κB signaling activation as well as intestinal barrier disruption. Clinical studies have shown that probiotic administration may protect against NEC, however there are safety concerns associated with the ingestion of large bacterial loads in preterm infants. Bacteria-free conditioned media (CM) from certain probiotic organisms have been shown to retain bioactivity including anti-inflammatory and cytoprotective properties without the risks of live organisms. We hypothesized that the CM from Lactobacillus acidophilus (La), Bifidobacterium infantis (Bi), and Lactobacillus plantarum (Lp), used separately or together would protect against NEC. A rodent model with intestinal injury similar to NEC was used to study the effect of CM from Lp, La/Bi, and La/Bi/Lp on the pathophysiology of NEC. All the CM suppressed NF-κB activation via preserved IκBα expression and this protected IκBα was associated with decreased liver activity of the proteasome, which is the degrading machinery for IκBα. These CM effects also caused decreases in intestinal production of the pro-inflammatory cytokine TNF-α, a downstream target of the NF-κB pathway. Combined La/Bi and La/Bi/Lp CM in addition protected intestinal barrier function by maintaining tight junction protein ZO-1 levels and localization at the tight junction. Double combined La/Bi CM significantly reduced intestinal injury incidence from 43% to 28% and triple combined La/Bi/Lp CM further reduced intestinal injury incidence to 20%. Thus, this study demonstrates different protective mechanisms and synergistic bioactivity of the CM from different organisms in ameliorating NEC-like intestinal injury in an animal model.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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".