Saccharomyces boulardii modulates necrotizing enterocolitis in neonatal mice by regulating the sirtuin 1/NF‑κB pathway and the intestinal microbiota

Zhang,Kun; Zhang,Xi; Lv,Anping; Fan,Sainan; Zhang,Jinping

doi:10.3892/mmr.2020.11138

Saccharomyces boulardii modulates necrotizing enterocolitis in neonatal mice by regulating the sirtuin 1/NF‑κB pathway and the intestinal microbiota

Authors:
- Kun Zhang
- Xi Zhang
- Anping Lv
- Sainan Fan
- Jinping Zhang
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Affiliations: Department of Pediatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China, Department of Obstetrics, Changning Maternity and Infant Health Hospital, Shanghai 200050, P.R. China, Department of Pediatrics, East Campus of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 201306, P.R. China
Published online on: May 7, 2020 https://doi.org/10.3892/mmr.2020.11138
Pages: 671-680
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Exaggerated inflammatory response and gut microbial dysbiosis play a crucial role in necrotizing enterocolitis (NEC). The probiotic Saccharomyces boulardii (SB) is a yeast that has a beneficial effect on NEC; however, the association between its protective effects and the regulation of the inflammation‑related sirtuin 1 (SIRT1)/nuclear factor‑κB (NF‑κB) signaling pathway and gut microbiota in NEC is unknown. In the present study, the NEC model was established by artificial feeding and lipopolysaccharide (LPS), hypoxia and hypothermia stimulation. Mice were divided into normal, control (artificial feeding), NEC and NEC + SB groups. Hematoxylin and eosin staining demonstrated that SB improved the pathological damage of the intestine caused by NEC in neonatal mice. Furthermore, downregulation of SIRT1 and upregulation of NF‑κB expression were confirmed by immunofluorescence staining, western blotting and reverse transcription‑quantitative PCR (RT‑qPCR) in NEC mice. SB treatment concurrently inhibited the NEC roles on the SIRT1 and NF‑κB pathway at both the protein and mRNA levels. Deletion of SIRT1 [SIRT1 knockout (KO)] in the intestine abolished all the effects of SB in NEC mice, including protection of pathological damage and inhibition of the SIRT1/NF‑κB pathway activation. The abundance of gut microbial composition, as determined by RT‑qPCR, was significantly decreased in the control group compared with the normal group. A further decrease in microbiota abundance was observed in the NEC group, and SB administration significantly improved the enrichment of gut microbiota in neonatal mice with NEC. As anticipated, the increased abundance of gut microbiota modulated by SB was markedly reduced in SIRT1KO NEC mice. The present study revealed that the protective role of SB on NEC was associated with the SIRT1/NF‑κB pathway and gut microbiota regulation.

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