Cryptosporidiosis modulates gut microbiome metabolism and the immune response in an infected host
Bibliographic record
Abstract
Abstract Background Cryptosporidiosis is a major global human health concern. Despite well-established methods, misdiagnosis remain common. Resulting incorrect clinical prescription often causes anti-microbial resistance development in the patients. Our understanding of the Cryptosporidium infection mechanism remains limited, compounding the difficulty of clinical diagnosis. Multi-omics approach has shown significant potential for addressing this limitation and, biomarker discovery towards rapid and accurate diagnostics. This study investigated the underlying biochemistry of host-microbiome-parasite relationships during infection. Methods C57BL/6J mice were infected with 1 × 105 Cryptosporidium parvum oocysts via oral gavage. Faecal samples were collected daily, while blood, liver tissues and luminal contents of the small and large intestines were collected 10 days post infection. High-resolution liquid chromatography and low-resolution gas chromatography coupled with mass spectrometry were used to analyse the proteomes and metabolomes of faeces, serum, liver, and luminal contents. Faecal samples were additionally subjected to 16S rRNA gene sequencing. Univariate and multivariate statistical analysis were applied to all datasets. Results Host and microbial energy pathways altered during infection. Glycolysis/citrate cycle metabolites, such as malate and lactate, were elevated in the large intestine. Short-chain fatty acids, formate and acetate, increased in the small intestine, while butanoate increased in the caecum-colon. This correlated with an increased abundance of bacteria associated with a stressed host environment, including Lactobacillus (small intestine) and Coriobacteriaceae (throughout the intestine, but more prominently in colon). The expression of host electron transfer flavoprotein, phosphoglycerate kinase and acetyl CoA binding proteins, yeast glyceraldehyde-3-phosphate dehydrogenase, and Lactobacillus glyceraldehyde-3-phosphate dehydrogenase significantly increased in the infected gut. Liver oxalate increase was also seen during infection. Conclusions The microbiome-parasite relationship is more influential than the previously thought host-parasite relationship, in mediating major biochemical changes in the mouse gut during cryptosporidiosis. Defining this parasite-microbiome interaction is the first step towards building a comprehensive cryptosporidiosis 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) | 0.000 | 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".