Gut microbiome dynamics in index patients colonized with extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales after hospital discharge and their household contacts. MODERN

The transmission of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) has been subject to many studies in clinical settings and in the community. However, not much is known about the impact of ESBL-PE acquisition on the gut microbiome composition. We analyzed gut microbiome dynamics of index patients colonized with ESBL-producing Escherichia coli (ESBL-Ec) or Klebsiella pneumoniae (ESBL-Kp) and their household contacts up to four months after hospital discharge of the index patient. Samples were collected from 3 index patients positive for ESBL-Kp and 5 index patients positive for ESBL-Ec and their respective household contacts (n=9) at day of hospital discharge, one week, two months and four months after discharge. In total, 5/9 household contacts were ESBL-PE positive at day of discharge. All 66 fecal samples were subjected to microbial profiling using 16S rRNA amplicon gene sequencing. Compared to household contacts, the alpha diversity of index patients was significantly lower (p smaller than 0.001) and a significant (p smaller than 0.05) separation between the two groups was observed based on beta diversity. In the index patients, Klebsiella and Escherichia-Shigella belonged to the top-10 most abundant genera, whereas in the household contacts that were culture positive for ESBL-Ec or ESBL-Kp, Escherichia-Shigella was only found at low abundance of smaller than 2%, while Klebsiella was absent. Principal component analysis of the samples from each household (i.e. index patient and respective household contact) showed a clear shift in microbiome composition, in 4 out of 8 index patients, from dissimilar to more similar to the household contact group. This suggests recovery of the microbiome to a healthier status, which was also reflected by de novo colonization of (health associated) taxa. In contrast, the four time-point samples of the household contacts clustered together indicating a stable microbiome composition over time irrespective of low-level ESBL-Ec or ESBL-Kp colonization. In conclusion, here we show that at the day of hospital discharge the microbiome composition of index patients is dissimilar from that of household contacts. Over time, signals of microbiome recovery were observed in half of the index patients. The stable microbiome composition in household contacts irrespective of low-level ESBL-Ec or ESBL-Kp colonization suggests that the gut microbiome in these healthy people provided colonization resistance against ESBL-PE outgrowth.