Objectives: To examine the impact of probiotics on the lung development of preterm birth of Bama pig. Methods: From April 2020 to October 2021, this animal experimental research was performed by setting up preterm (birth at gestation 104 d), full-term (birth at gestation 113 d), preterm with probiotics (birth at gestation 104 d treated with probiotics given at 3 d after birth), and full-term with probiotics (birth at gestation 113 d treated with probiotics given at 3 d after birth) groups and using the preterm Bama minipig model, the body weights were recorded and lung, ileum, and intestinal content samples were collected at birth, 4 days, 9 days, and 21 days after births of the piglets in preterm and full-term groups, the same samples were collected on 9 days after births of the piglets in preterm with probiotics and full-term with probiotics groups. The body weight and radial alveolar counts (RAC) were compared to evaluate the lung development of the piglets. The lengths of ileal villus were compared to evaluate the development of ileum. The composition structures of bacteria in ileum were analyzed by 16 S rRNA sequencing. The statistical analyses between different groups were performed by t test. Results: There were totally 30 piglets (16 female piglets and 14 male piglets) involving 12 piglets in preterm and full-term groups respectively and 3 piglets in preterm with probiotics and full-term with probiotics groups respectively. The body weights of the piglets in preterm group were lower than those in full-term group at 4, 9 and 21 d after birth ((507±27) vs. (694±56) g, (620±35) vs. (1 092±154) g, (1 660±210) vs. (2 960±418) g,t=2.96, 2.99, 2.78, all P<0.05). The alveolarization of the preterm piglets at 9 days after birth was significantly lower than that of the full-term piglets at the equivalent time point (4.00±0.29 vs. 6.11±0.35, t=4.64, P<0.01). The bacteria genus with the highest abundance in ileum were all different between the preterm and the full-term groups at 4, 9 and 21 d after birth (4 d Escherichia-Shigella (26.63%) and Enterococcus (30.48%) respectively;9 d Turicibacter (35.94%) and Lactobacillus (27.33%) respectively;21 d Escherichia-Shigella (28.02%) and Lactobacillus (46.29%) respectively). The heights of ileal villus of the preterm piglets at 9 d after birth were significantly lower than those of the full-term minipigs at the equivalent time point ((297±21) vs. (411±32) μm, t=3.01, P=0.007).There were both no differences in the body weight and alveolarization ((692±36) vs. (767±67) g, 5.44±0.34 vs. 5.89±0.26, t=0.74, 1.04, both P>0.05) between the piglets in preterm with probiotics group and those in full-term with probiotics group. Turicibacter was the dominant genus in the piglets of both preterm with probiotics and the full-term with probiotics groups. The heights of ileal villus of the piglets in preterm with probiotics group were significantly longer that those of the piglets in preterm group ((371±13) vs. (297±21) μm, t=3.04, P=0.006), and were both not significantly different from those of the piglets in full-term with probiotics group and full-term group ((371±13) vs. (338±12) and (411±32) μm, t=1.90, 1.15, both P>0.05). Conclusions: Premature birth could impact the lung alveolarization of piglets. The probiotics could improve the lung alveolarization of preterm minipigs by promoting the development of ileum.
目的： 探索益生菌干预在早产巴马猪生后肺脏发育中的作用。 方法： 动物实验研究，2020年4月至2021年10月利用已成功建立的30只早产巴马猪模型，将仔猪分为早产组（妊娠104 d出生）、足月组（妊娠113 d出生）、早产益生菌干预组（妊娠104 d出生后第3天开始给予口服益生菌）和足月益生菌干预组（妊娠113 d出生后第3天开始给予口服益生菌），分别记录早产组和足月组仔猪出生后即刻、生后4、9、21 d以及早产益生菌干预组和足月益生菌干预组仔猪生后9 d后的体重并收集肺组织、回肠组织和肠道内容物。通过比较体重、辐射状肺泡计数来评估仔猪发育情况，通过测量回肠绒毛高度评估回肠发育情况，通过菌群16 S核糖体RNA分析评估回肠内容物的菌类构成，组间比较采用t检验。 结果： 30只仔猪中雌性16只、雄性14只。早产组和足月组各12只，早产益生菌干预组和足月益生菌干预组各3只。早产组仔猪生后4、9、21 d的体重均分别低于足月组生后4、9、21 d［（507±27）比（694±56）g、（620±35）比（1 092±154）g、（1 660±210）比（2 960±418）g，t=2.96、2.99、2.78，均 P<0.05］，早产组仔猪出生9 d的辐射状肺泡计数低于足月组9 d的仔猪［（4.00±0.29）比（6.11±0.35）个，t=4.64，P<0.01］。早产组和足月组仔猪在生后不同时间点有不同的高丰度回肠菌属，生后4 d时分别为大肠杆菌志贺菌属26.63%和肠球菌属30.48%；出生9 d时分别为苏黎世杆菌属35.94%和乳杆菌属27.33%；出生21 d时分别为大肠杆菌志贺菌属28.02%和乳杆菌属46.29%。早产组9 d仔猪的回肠绒毛高度小于足月组9 d的仔猪［（297±21）比（411±32）μm，t=3.01，P=0.007］。早产益生菌干预组和足月益生菌干预组的仔猪体重、辐射状肺泡计数差异均无统计学意义［（692±36）比（767±67）g、（5.44±0.34）比（5.89±0.26）个，t=0.74、1.04，均P>0.05］。早产益生菌干预组及足月益生菌干预组的回肠优势菌属均为苏黎世杆菌属，早产益生菌干预组仔猪的回肠绒毛高度大于早产组9 d的仔猪［（371±13）比（297±21）μm，t=3.04，P=0.006］，与足月益生菌干预组仔猪和足月组9 d仔猪的差异均无统计学意义［（371±13）比（338±12）和（411±32）μm，t=1.90、1.15，均P>0.05］。 结论： 早产会影响肺发育中的肺泡化进程。早产生后的益生菌干预可能通过改善肠道发育促进肺泡化进程。.