Early supplementation with live combined Bacillus subtilis and Enterococcus faecium: association with feeding intolerance and gut microbiota composition in antibiotic-exposed preterm infants.
Ye C, Li L, et al. • Frontiers in cellular and infection microbiology • 2026
Early LCBE supplementation was associated with a significant reduction in the incidence of feeding intolerance in antibiotic-exposed preterm infants, accompanied by favorable gut microbiota modulation including suppression of opportunistic pathogen overgrowth and preservation of beneficial commensal taxa.
Key Findings
Results
LCBE supplementation was associated with a significantly lower incidence of feeding intolerance in antibiotic-exposed preterm infants.
Feeding intolerance incidence was 17.07% in the probiotic group versus 44.74% in the non-probiotic group.
Adjusted OR = 0.156 (95% CI: 0.050–0.491, p = 0.001).
79 antibiotic-exposed preterm infants were enrolled: probiotic group (n = 41) and non-probiotic group (n = 38).
Study was conducted in a NICU setting between February 2020 and April 2022.
The intervention was prospectively observed, not randomized.
Results
The protective association of LCBE supplementation with feeding intolerance became evident only during the post-supplementation period.
The protective association was observed specifically during postnatal days 21–28.
This pattern suggests a delayed but sustained effect of LCBE supplementation.
No protective association was noted in earlier time periods prior to this window.
Results
LCBE supplementation was associated with suppression of potentially pathogenic bacteria in the gut microbiota.
Potentially pathogenic genera suppressed included Enterococcus and Klebsiella.
Gut microbiota composition was analyzed via 16S rRNA gene sequencing of 274 fecal samples (144 from the probiotic group, 130 from the non-probiotic group).
The probiotic used was a live combined preparation of Bacillus subtilis and Enterococcus faecium (LCBE).
Suppression of opportunistic pathogens was observed in the context of antibiotic exposure, a setting known to promote dysbiosis.
Results
LCBE supplementation was associated with preservation of beneficial gut bacterial genera in antibiotic-exposed preterm infants.
Beneficial genera preserved included Bifidobacterium and Lactobacillus.
These microbial shifts were accompanied by a more stable and mature gut microbiota profile.
Early antibiotic exposure frequently induces gut dysbiosis in preterm infants, making preservation of commensals clinically relevant.
Results
LCBE supplementation was well-tolerated with no treatment-related adverse events reported.
No adverse events attributed to LCBE were observed in the probiotic group (n = 41).
The study population consisted of antibiotic-exposed preterm infants in the NICU, considered a high-risk and vulnerable population.
Safety was assessed prospectively as part of clinical data collection.
Background
Early antibiotic exposure in preterm infants frequently induces gut dysbiosis, representing the clinical context for this study.
High-quality clinical evidence for probiotics in antibiotic-exposed preterm infants was described as limited at the time of the study.
The study specifically enrolled antibiotic-exposed preterm infants admitted to the NICU.
LCBE was investigated as a potential intervention to mitigate antibiotic-induced microbiota disruption.
What This Means
This research suggests that giving preterm babies in intensive care a specific probiotic supplement — a combination of two bacteria called Bacillus subtilis and Enterococcus faecium (called LCBE) — may help reduce a common and serious feeding problem. In the study, only about 17% of preterm babies who received the probiotic had feeding intolerance (difficulty tolerating milk feeds), compared to nearly 45% of babies who did not receive it. Feeding intolerance is a significant concern in premature infants because it can delay nutrition and slow growth and recovery. Interestingly, the benefit appeared to emerge around three to four weeks after birth rather than immediately, suggesting the probiotic's effects build over time.
The researchers also examined the gut bacteria of these infants using genetic sequencing of stool samples. Babies who received the probiotic had lower levels of potentially harmful bacteria like Enterococcus and Klebsiella, and better preservation of beneficial bacteria like Bifidobacterium and Lactobacillus. This is particularly important because premature babies often receive antibiotics, which can disrupt the normal development of gut bacteria and leave infants vulnerable to colonization by harmful microbes. The probiotic appeared to help maintain a healthier, more stable bacterial community in the gut despite antibiotic exposure.
This research suggests that early probiotic supplementation with LCBE may be a safe and practical addition to care for antibiotic-treated preterm infants in neonatal intensive care units, potentially reducing feeding complications and supporting healthier gut development. The study was observational rather than a randomized controlled trial, so the findings indicate an association rather than definitive proof of cause and effect, and further research would be needed to confirm these results.
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Ye C, Li L, Zhang H, Lyu Q, Xu Y, Li Y. (2026). Early supplementation with live combined Bacillus subtilis and Enterococcus faecium: association with feeding intolerance and gut microbiota composition in antibiotic-exposed preterm infants.. Frontiers in cellular and infection microbiology. https://doi.org/10.3389/fcimb.2026.1826157