Gut microbiota and fecal metabolomic alterations in hospitalized patients with Staphylococcus aureus infection: an exploratory multi-omics study.

Alpha-diversity indices were lower in the SAI group compared to healthy controls.

• The study included 16 hospitalized patients with microbiologically confirmed SAI and 10 healthy controls.
• First qualified fecal sample was collected within 7 days after microbiological confirmation.
• Fifteen of 16 patients had received antimicrobial treatment before sampling, which likely confounds diversity differences.
• None of the healthy controls had received antibiotics before fecal collection.

Bray-Curtis PERMANOVA revealed a statistically significant but modest group-associated difference in gut microbial community composition between SAI patients and healthy controls.

• PERMANOVA results: F = 2.8654, R² = 0.1067, P = 0.0001.
• The R² value of 0.1067 indicates that group membership explained only approximately 10.7% of the variance in community composition.
• PERMDISP was not significant (P = 0.0885), suggesting the compositional difference was not driven by differences in dispersion.
• The authors describe the difference as 'statistically significant but modest.'

ANCOM-BC2 identified four bacterial genera with robustly higher bias-corrected abundance in the SAI group: Corynebacterium, the [Clostridium] innocuum group, Enterococcus, and Eggerthella.

• Differential abundance was assessed using ANCOM-BC2 with Benjamini-Hochberg correction and pseudo-count sensitivity analysis.
• Effect directions for all four genera remained positive in culture-confirmed and respiratory-infection-only subgroup analyses.
• Not all four genera retained pseudo-count-robust significance in sensitivity analyses.
• Genus-level analysis was chosen as the primary level of resolution for differential abundance testing.

Untargeted fecal metabolomics detected 2,956 features, with 381 candidate features identified using VIP > 1 and raw P < 0.05.

• LC-MS/MS-based untargeted metabolomics was used to analyze fecal metabolites.
• Of the 2,956 features detected, 2,491 had putative MS/MS-based annotations.
• 381 candidate features were identified using VIP > 1 and raw P < 0.05 as thresholds.
• Exploratory enrichment signals involved tryptophan, glutathione, sulfur, bile acid, amino acid, and lipid metabolism.
• These enrichment signals were explicitly 'not regarded as FDR-confirmed.'

No clinical-omics associations remained significant after FDR correction.

• Associations between clinical indicators (inflammatory and organ-function indicators) and omics data were explored.
• No association survived false discovery rate correction.
• The study was designed as an exploratory observational single-center study with a small sample size (n=26 total).
• The authors characterize all findings as 'preliminary and hypothesis-generating rather than S. aureus-specific signatures.'

The gut microbiota and metabolomic alterations observed in SAI patients cannot be attributed specifically to S. aureus infection due to extensive antimicrobial pre-exposure and other confounders.

• Fifteen of 16 SAI patients had received antimicrobial treatment before fecal sampling.
• Potential confounders include antimicrobial treatment, hospitalization, disease severity, and other clinical interventions.
• The authors explicitly state these patterns 'cannot be separated from treatment, hospitalization, disease severity, and other clinical interventions.'
• The study design is characterized as 'single-center exploratory observational,' limiting causal or pathogen-specific inference.