A novel cocktail of probiotics designed to mitigate meconium-derived antibiotic-resistant Enterobacteriaceae

Preterm birth is a public health concern, and it has been listed as one of the focuses under the Good Health and Well-Being of The Sustainable Development Goals in Malaysia, Singapore, and Brunei Darussalam. Preterm infants are associated with a higher risk of mortality and the development of morbidities such as sepsis, necrotizing enterocolitis, and hyperbilirubinemia. Besides, they have an immature gastrointestinal tract with weak barrier function and poor immunity. The perturbation of neonatal gut microbiome development could increase susceptibility to various illnesses. Studies have reported that intestinal carriage of Enterobacteriaceae has been linked to the development of necrotizing enterocolitis and sepsis in preterm infants. Besides, there is limited knowledge on the culturable Enterobacteriaceae population, particularly from the meconium (first stool) of preterm infants. Furthermore, the emergence of antibiotic-resistant Enterobacteriaceae among preterm infants population, which could be driven by infants' early and long-term exposure to antibiotics, is of concern as infections with these microorganisms are challenging to treat and could lead to detrimental outcomes. Therefore, alternative therapies such as probiotics could be used to decrease potential gut pathogenic Enterobacteriaceae. Nonetheless, there is still limited knowledge on the optimum dose, frequency, duration of treatment, and combination of probiotics to eradicate these pathogens effectively. This study aims to develop a novel consortium of 3 probiotic strains and demonstrate their inhibitory effect against antibiotic-resistant Enterobacteriaceae clinical isolates obtained from meconium samples of very preterm and very low birth weight infants in Malaysia. The antagonistic activity of probiotic strains will be evaluated, and the most effective probiotic combination against a selected antibiotic-resistant clinical isolate will be tested in vivo using a murine infection model.