John Penders

Aim: This study aimed to examine the impact of fecal water (FW) of active and remissive Crohn's disease (CD) patients on mucin degradation and epithelial barrier function. Methods: FW and bacterial membrane vesicles (MVs) were isolated from fresh fecal samples of six healthy controls (HCs) and 12 CD patients. Bacterial composition was determined by 16S rRNA gene amplicon sequencing. Results: In vitro FW-induced mucin degradation was higher in CD samples versus HC (p < 0.01), but not associated with specific bacterial genera. FW of three remissive samples decreased transepithelial electrical resistance in Caco-2 cells by 78–87% (p < 0.001). MVs did not induce barrier alterations. Conclusion: The higher mucin-degradation capacity of CD-derived FW might suggest contributions of microbial products to CD pathophysiology.

Objectives. Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-Ec) are frequently acquired during international travel, contributing to the global spread of antimicrobial resistance. Human-adapted ESBL-Ec are predicted to exhibit increased intestinal carriage duration, resulting in a higher likelihood of onward human-to-human transmission. Yet, bacterial determinants of increased carriage duration are unknown. Previous studies analysed small traveller cohorts, with short follow-up times, or did not employ high-resolution molecular typing, and were thus unable to identify bacterial traits associated with long-term carriage after recent acquisition. We aimed to identify which ESBL-Ec lineages are associated with increased carriage duration after return from international travel. Methods. In a prospective cohort study of 2001 international travellers, we analysed 160 faecal ESBL-Ec isolates from all 38 travellers who acquired ESBL-Ec during travel and subsequently carried ESBL-Ec for at least 12 months after return, by whole-genome sequencing. For 17 travellers, we confirmed the long-term carriage of ESBL-Ec strains through single nucleotide variant typing. To identify determinants of increased carriage duration, we compared the 17 long-term carriers (≥12 months of carriage) with 33 age-, sex- and destination-matched short-term carriers (<1 month of carriage). Long-read sequencing was employed to investigate long-term ESBL plasmid carriage. Results. We show that in healthy travellers with very low antibiotic usage, extra-intestinal pathogenic lineages of E. coli (ExPEC) are significantly more likely to persist than other E. coli lineages. The long-term carriage of E. coli from ExPEC lineages is mainly driven by sequence type 131 and phylogroup D E. coli . Conclusions. Although ExPEC lineages frequently cause extra-intestinal infections such as bloodstream infections, our results indicate that ExPEC lineages are also efficient intestinal colonizers, which potentially contributes to their onward tra