Probiotics and human milk differentially influence the gut microbiome and NEC incidence in preterm pigs

Authors: MELENDEZ HEBIB, VALERIA - Baylor College Of Medicine; TAFT, DIANA - University Of California (UCLA); STOLL, BARBARA - Baylor College Of Medicine; LIU, JINXIN - University Of California (UCLA); CALL, LEE - Baylor College Of Medicine; GUTHRIE, GREGORY - Baylor College Of Medicine; JENSEN, NICK - University Of California (UCLA); HAIR, AMY - Baylor College Of Medicine; MILLS, DAVID - University Of California (UCLA); Burrin, Douglas - Doug

Submitted to: Gut Microbes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/29/2023
Publication Date: 5/31/2023
Citation: Melendez Hebib, V., Taft, D., Stoll, B., Liu, J., Call, L., Guthrie, G., Jensen, N., Hair, A.B., Mills, D.A., Burrin, D.G. 2023. Probiotics and human milk differentially influence the gut microbiome and NEC incidence in preterm pigs. Gut Microbes. 15(11):2585. https://doi.org/10.3390/nu15112585.
DOI: https://doi.org/10.3390/nu15112585

Interpretive Summary: Premature birth is a worldwide health concern where, babies are born too early and have a higher the risk of death, serious disability, or other health issues. More than 15 million infants are born preterm, before their due date at 37 weeks of pregnancy every year. In the United States, more than one in 10 children are born preterm. Necrotizing enterocolitis (NEC) is a serious disease that occurs in preterm babies. The risk of NEC increases when babies are born early, are fed infant formula, and have certain bacteria in their intestine. Some good bacteria, called probiotics, have been shown to reduce the risk of NEC in babies. In this study, we used our animal model of preterm baby piglets to test whether a probiotic called Bifidobacterium longum subsps infantis (BL. infantis) and a sugar called sialylactose (3’SL), that is found in breast milk, affected the risk of NEC. We found that giving BL. infantis and 3’SL alone or in together, did not prevent NEC in baby piglets. However, we found that donor human milk did prevent NEC compared to infant formula-fed piglets. We also found that a certain bacteria, especially Clostridium perfringens, was more abundant in the intestine of piglets that were fed infant formula and had NEC. Our study shows that using BL. infantis and 3SL may not be enough to prevent NEC when babies are not being fed breast milk and that some specific bacteria in the gut may play a role in causing this disease.

Technical Abstract: Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in preterm infants. Major risk factors are prematurity, formula feeding, and gut microbial colonization. Microbes have been linked to NEC, yet there is no evidence of causal species and select probiotics have been shown to reduce NEC incidence in infants. In this study, we evaluated the effect of the probiotic, Bifidobacterium longum subsp. infantis (BL. infantis), alone and in combination with a human milk oligosaccharide (HMO), sialylactose (3'SL), on the microbiome and incidence of NEC in preterm piglets fed an infant formula diet. We studied 50 preterm piglets randomized between 5 treatments: 1) Preterm infant formula, 2) Donor human milk (DHM), 3) Infant formula + 3'SL, (4) Infant formula + BL. infantis, (5) Infant formula and BL. infantis + 3’SL. NEC incidence and severity were assessed by evaluation of tissue from all segments of the GI tract. The gut microbiota composition was assessed both daily and terminally by 16S and whole genome sequencing (WGS) of rectal stool samples and intestinal contents. Dietary BL. infantis and 3’SL supplementation had no effect, yet DHM significantly reduced the incidence of NEC and the abundance of BL. infantis in the gut contents negatively correlated with disease severity. Clostridium sensu stricto 1 and Clostridium perfringens were significantly more abundant in NEC and positively correlated with disease severity. Our results suggest pre- and probiotics are not sufficient for protection from NEC in an exclusive formula-based diet. The results highlight differences in microbial species positively associated with both diet and NEC incidence.