Klingenberg, C. | bioRxiv Science

bioRxiv2025

Metabolic reprogramming of the infant gut by bifidobacteria-based probiotics drives exclusion of antibiotic-resistant pathobionts

Early-life probiotics have emerged as a promising strategy to combat the global emergency of antimicrobial resistance by enhancing gut resilience in infants. However, how exactly probiotic bacteria affect resistant opportunistic pathogens, i.e., pathobionts, remains nascent. We investigated effects of probiotic supplementation in 152 full-term, healthy Tanzanian infants, a sub-cohort of the ProRIDE trial (NCT04172012). Administration of oral probiotics during the first 4 weeks of life led to enhanced gut colonization by the probiotic Bifidobacterium species while suppressing pathobionts such as extended-spectrum {beta}-lactamase-producing Enterobacterales (ESBL-E). Integration of metagenomics with metabolomics revealed that probiotics decreased resistome load and mobilome richness at 6 weeks, with concurrent shifts in metabolome. Specifically, the intervention increased fecal lactate and pyruvate and reduced cross-feeding pathways leading to propionate and butyrate, which partly explained the reduced ESBL-E carriage. Our findings provide mechanistic insights into how probiotic-driven Bifidobacterium colonization modulates infant gut ecosystem to attenuate antimicrobial resistance in infancy.

microbiology↗

bioRxiv2023

Evaluating The Efficacy Of Endotracheal Epinephrine Administration At Standard Versus High Dose During Resuscitation Of Severely Asphyxiated Newborn Lambs: A Randomized Preclinical Study

BackgroundEpinephrine treatment is recommended during neonatal resuscitation, if ventilation and chest compressions are ineffective. Endotracheal administration is an option, if the preferred intravenous route is unavailable. We aimed to determine the efficacy of endotracheal epinephrine for achieving return of spontaneous circulation (ROSC), and maintaining physiological stability after ROSC, at standard and higher dose, in severely asphyxiated newborn lambs. MethodsNear-term fetal lambs were instrumented for physiological monitoring, and asphyxiated until asystole. Resuscitation was commenced with ventilation and chest compressions as per ILCOR recommendations. Lambs were randomly allocated to: IV Saline placebo (5 ml/kg, n=6), IV Epinephrine (20 micrograms/kg, n=9), Standard-dose ET Epinephrine (100 micrograms/kg, n=9), and High-dose ET Epinephrine (1 mg/kg, n=9). After three allocated treatment doses, rescue IV Epinephrine was administered if ROSC had not occurred. Lambs achieving ROSC were ventilated and monitored for 60 minutes before euthanasia. Brain histology was assessed for micro-hemorrhage. ResultsROSC in response to allocated treatment (without rescue IV Epinephrine) occurred in 1/6 Saline, 9/9 IV Epinephrine, 0/9 Standard-dose ET Epinephrine, and 7/9 High-dose ET Epinephrine lambs respectively. Three Saline, six Standard-dose ET Epinephrine, and one High-dose ET Epinephrine lambs achieved ROSC after rescue IV Epinephrine. Blood pressure during CPR increased after treatment with IV Epinephrine and High-dose ET Epinephrine, but not Saline or Standard-dose ET Epinephrine. After ROSC, both ET Epinephrine groups had lower pH, higher lactate, and higher blood pressure than the IV Epinephrine group. Cortex micro-hemorrhage was more frequent in the High-dose ET Epinephrine lambs (8/8 lambs examined, versus 3/8 in IV Epinephrine lambs). ConclusionsThe currently recommended dose of ET Epinephrine was ineffective in achieving ROSC. In the absence of convincing clinical or preclinical evidence of efficacy, use of ET Epinephrine at this dose may not be appropriate. High-dose ET Epinephrine requires further evaluation before clinical translation.

physiology↗