Metagenomic insights into potential horizontal transfer of resistance/virulence genes in gut microbiota from patients with Crohn disease.

BACKGROUND

Unraveling the potential horizontal transfer of resistance genes/virulence genes (RGs/VGs) in gut microbiota from patients with Crohn disease (CD) is an interesting but poorly characterized issue.

METHODS

Quantitative assessment was performed to estimate the relative abundance and diversity of RGs/VGs/mobile genetic elements (MGEs). Differential analysis was applied to identify the CD-specific enriched genetic subtypes. A species-RGs/VGs/MGEs association network was constructed to explore possible co-occurrence patterns of these genetic elements across potential microbial hosts. Integrated with topological metrics and Zi-Pi computational modeling, co-occurrence network analysis was conducted to characterize potential associations among RGs, VGs, and MGEs.

RESULTS

Comparative metagenomic analyses indicated that the microbiome in group CD exhibited significantly higher relative abundance of RGs compared to that in healthy controls (HC; P = .040), with 131 specific RG/VG subtypes (eg, acrA/T6SS) exhibiting marked enrichment (P < .05). The co-occurrence network revealed intensified interconnectivity between RGs/VGs and MGEs in group CD, in which MGEs accounted for 71% of network nodes (vs 60.80% in HC), and 99.14% of the edges were positively correlated (vs 93.60% in HC). Network topology and Zi-Pi analysis further suggested reduced modularity (0.709 vs 0.979 in HC) and enhanced intergene connectivity (average degree: 12.288 vs 2.156; average weighted degree: 23.359 vs 3.688 in HC). There were no network hubs (0 vs 5 in HC) but abundant modular hubs (60 vs 25 in HC), peripheral nodes (2317 vs 1549 in HC), and connectors (61 vs 36 in HC), which may reflect conditions favorable for enhanced gene transfer potential. Cross-species transfer events were predicted across clinical-environmental-commensal boundaries, exemplified by tet(M) dissemination between Clostridioides difficile and Bacteroides sp., probably implying progressive erosion of ecological barriers.

CONCLUSIONS

Collectively, we inferred that the gut microbiome of CD patients might represent a high-risk reservoir for the horizontal transfer of pathogenic determinants, which may pose a potential threat for public health and biosecurity.