Premature infants are at risk of developing necrotizing enterocolitis (NEC). Intravenous antibiotics (AB) are given to NEC patients to avert sepsis, despite enteral AB being more implicit but is hardly used as there is fear of AB resistance. Fecal microbiota transplantation (FMT) has been found to protect against NEC in animal studies, but the relationship between AB and FMT in newborns has not previously been investigated. For a study, NEC was combated by enteral AB administration followed by rectal FMT without affecting AB resistance or systemic immunity. Researchers investigated host and gut microbiota responses to AB, FMT, or a sequential combination in preterm piglets. For four days post-cesarean delivery, Preterm piglets (n=67) were treated with oro-gastric neomycin (50 mg/kg/d) and amoxicillin-clavulanate (50/12.5 mg/kg/d) (hereafter AB) and then, given rectal FMT from healthy suckling piglet donors. The protection of the small intestine and stomach was preserved by AB, whereas FMT protected the colon best. Despite this, the sequential combination therapy did not offer any NEC protection. In addition, minor modifications in the gut microbiota composition were observed, even though AB therapy escalated AB resistance and reduced species diversity among coliform bacteria and Enterococci, which were both partially revoked by FMT. Enteral AB therapy inhibited cellular and functional systemic immune development, which was not reversed by subsequent FMT. In terms of NEC development, a hostile relationship between enteral AB and FMT was discovered. The success of AB therapies, FMT formulations, doses, treatment durations, and administration techniques may all have an impact on the final result. The findings call into question the use of enteral AB and FMT in preterm infants.