The Detrimental Effects of Peripartum Antibiotics on Gut Proliferation and Formula Feeding Injury in Neonatal Mice Are Alleviated with Lactobacillus rhamnosus GG.
The Detrimental Effects of Peripartum Antibiotics on Gut Proliferation and Formula Feeding Injury in Neonatal Mice Are Alleviated with Lactobacillus rhamnosus GG.
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DOI：
10.3390/microorganisms11061482
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发表时间：
2023-06-01
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
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围产期抗生素会对发育中的肠道微生物组产生负面影响，并与坏死性小肠结肠炎（NEC）有关。围产期抗生素增加NEC风险的机制以及有助于减轻这种风险的策略仍然知之甚少。在这项研究中，我们确定了围产期抗生素增加新生儿肠道损伤的机制，并评估了益生菌是否能防止围产期抗生素增强的肠道损伤。为了实现这一目标，我们给怀孕的C57 BL 6小鼠施用广谱抗生素或无菌水，并通过配方喂养诱导其幼崽的新生儿肠道损伤。我们发现，与对照组相比，暴露于抗生素的幼崽绒毛高度、隐窝深度、肠嗅调节蛋白4和增殖细胞核抗原降低，表明围产期抗生素损害了肠道增殖。当使用配方奶喂养来诱导NEC样损伤时，与对照组相比，在接触抗生素的幼崽中观察到更严重的肠道损伤和细胞凋亡。补充益生菌鼠李糖乳杆菌GG（LGG）降低了抗生素增强的配方诱导的肠道损伤的严重程度。在补充LGG的幼崽中观察到肠道增殖细胞核抗原增加和Gpr 81-Wnt途径激活，表明益生菌部分恢复了肠道增殖。我们的结论是，围产期抗生素加强新生儿肠道损伤，抑制肠道增殖。补充LGG通过激活Gpr 81-Wnt通路和恢复围产期抗生素损害的肠道增殖来减少肠道损伤。我们的研究结果表明，出生后益生菌可能是有效的，以减轻风险增加NEC与围产期抗生素暴露早产儿。
Peripartum antibiotics can negatively impact the developing gut microbiome and are associated with necrotizing enterocolitis (NEC). The mechanisms by which peripartum antibiotics increase the risk of NEC and strategies that can help mitigate this risk remain poorly understood. In this study, we determined mechanisms by which peripartum antibiotics increase neonatal gut injury and evaluated whether probiotics protect against gut injury potentiated by peripartum antibiotics. To accomplish this objective, we administered broad-spectrum antibiotics or sterile water to pregnant C57BL6 mice and induced neonatal gut injury to their pups with formula feeding. We found that pups exposed to antibiotics had reduced villus height, crypt depth, and intestinal olfactomedin 4 and proliferating cell nuclear antigen compared to the controls, indicating that peripartum antibiotics impaired intestinal proliferation. When formula feeding was used to induce NEC-like injury, more severe intestinal injury and apoptosis were observed in the pups exposed to antibiotics compared to the controls. Supplementation with the probiotic Lactobacillus rhamnosus GG (LGG) reduced the severity of formula-induced gut injury potentiated by antibiotics. Increased intestinal proliferating cell nuclear antigen and activation of the Gpr81-Wnt pathway were noted in the pups supplemented with LGG, suggesting partial restoration of intestinal proliferation by probiotics. We conclude that peripartum antibiotics potentiate neonatal gut injury by inhibiting intestinal proliferation. LGG supplementation decreases gut injury by activating the Gpr81-Wnt pathway and restoring intestinal proliferation impaired by peripartum antibiotics. Our results suggest that postnatal probiotics may be effective in mitigating the increased risk of NEC associated with peripartum antibiotic exposure in preterm infants.
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影响因子：
3.5
作者：
Flanagan DJ;Austin CR;Vincan E;Phesse TJ
通讯作者：
Phesse TJ
影响因子：
4.5
作者：
Chen YY;Zhao X;Moeder W;Tun HM;Simons E;Mandhane PJ;Moraes TJ;Turvey SE;Subbarao P;Scott JA;Kozyrskyj AL
通讯作者：
Kozyrskyj AL
影响因子：
7.2
作者：
通讯作者：
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影响因子：
3
作者：
Chen, Wen-Yin;Lo, Yu-Cheng;Hung, Miao-Chiu
通讯作者：
Hung, Miao-Chiu
影响因子：
4.5
作者：
Chaaban H;Patel MM;Burge K;Eckert JV;Lupu C;Keshari RS;Silasi R;Regmi G;Trammell M;Dyer D;McElroy SJ;Lupu F
通讯作者：
Lupu F