Capturing the antibiotic resistome of preterm infants reveals new benefits of probiotic supplementation

Abstract

Background Probiotic use in preterm infants can mitigate the impact of antibiotic exposure and reduce rates of certain illnesses; however, the benefit on the gut resistome, the collection of antibiotic resistance genes, requires further investigation. We hypothesized that probiotic supplementation of early preterm infants (born < 32-week gestation) while in hospital reduces the prevalence of antibiotic resistance genes associated with pathogenic bacteria in the gut. We used a targeted capture approach to compare the resistome from stool samples collected at the term corrected age of 40 weeks for two groups of preterm infants (those that routinely received a multi-strain probiotic during hospitalization and those that did not) with samples from full-term infants at 10 days of age to identify if preterm birth or probiotic supplementation impacted the resistome. We also compared the two groups of preterm infants up to 5 months of age to identify persistent antibiotic resistance genes. Results At the term corrected age, or 10 days of age for the full-term infants, we found over 80 antibiotic resistance genes in the preterm infants that did not receive probiotics that were not identified in either the full-term or probiotic-supplemented preterm infants. More genes associated with antibiotic inactivation mechanisms were identified in preterm infants unexposed to probiotics at this collection time-point compared to the other infants. We further linked these genes to mobile genetic elements and Enterobacteriaceae, which were also abundant in their gut microbiomes. Various genes associated with aminoglycoside and beta-lactam resistance, commonly found in pathogenic bacteria, were retained for up to 5 months in the preterm infants that did not receive probiotics. Conclusions This pilot survey of preterm infants shows that probiotics administered after preterm birth during hospitalization reduced the diversity and prevented persistence of antibiotic resistance genes in the gut microbiome. The benefits of probiotic use on the microbiome and the resistome should be further explored in larger groups of infants. Due to its high sensitivity and lower sequencing cost, our targeted capture approach can facilitate these surveys to further address the implications of resistance genes persisting into infancy without the need for large-scale metagenomic sequencing.

Emerging issues in probiotic safety: 2023 perspectives

“…The analysis must consider if the probiotic is being developed for broad distribution to generally healthy consumers (foods or supplements, for which a reasonable certainty of no harm is the general standard) or restricted distribution for patient populations (drugs). Since probiotics have the potential to exacerbate 54 or mitigate 55 the reservoir of AR genes harbored in humans, a case-by-case approach to safety is likely needed. Previous authors have suggested systematic approaches to considering this issue.…”

Maternal-infant antibiotic resistance genes transference: what do we know?

“… Azithromycin, erythromycin 25 Macrolides Respiratory, intestine, gynecological, urogenital and skin infections, chlamydia infections and syphilis. Ciprofloxacin, norfloxacin 26 , 27 Quinolones Serious gram-negative bacterial infections. Clindamycin 28 , 29 Lincomycin Respiratory, skin, blood, female reproductive organ, and internal organ infections.…”

“…In premature babies, probiotic supplementation may increase protection against harmful bacteria and reduce the negative impact of antibiotics on the microbiome and resistome of the gut 26 . A different study demonstrated that administering probiotics to preterm infants during hospitalization after birth decreased the gut microbiome’s resistance gene diversity and prevented its persistence 27 .…”

Decoding Quetiapine's Impact: Antibiotic Efflux, Cell Membrane and Cell Wall Synthesis Genes in the Mouse Fecal Resistome

“…Analysis of Target Capture Sequencing Data. Sequenced reads were analyzed as described by Guitor et al 19 with a few modi cations. Paired sequencing reads were trimmed using skewer (version 0.2.2) 20 and deduplicated using dedupe.sh from BBMap (version 38.57) 21 .…”