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补充丁酸梭菌通过重塑宫内生长受限哺乳仔猪的肠道微生物群组成和胆汁酸谱来调节脂质代谢。

Supplemental Clostridium butyricum modulates lipid metabolism by reshaping the gut microbiota composition and bile acid profile in IUGR suckling piglets.

作者信息

Zhang Xin, Yun Yang, Lai Zheng, Ji Shuli, Yu Ge, Xie Zechen, Zhang Hao, Zhong Xiang, Wang Tian, Zhang Lili

机构信息

College of Animal Science and Technology, Nanjing Agricultural University, 210095, Nanjing, Jiangsu, China.

出版信息

J Anim Sci Biotechnol. 2023 Mar 13;14(1):36. doi: 10.1186/s40104-023-00828-1.

Abstract

BACKGROUND

Intrauterine growth restriction (IUGR) can cause lipid disorders in infants and have long-term adverse effects on their growth and development. Clostridium butyricum (C. butyricum), a kind of emerging probiotics, has been reported to effectively attenuate lipid metabolism dysfunctions. Therefore, the objective of this study was to investigate the effects of C. butyricum supplementation on hepatic lipid disorders in IUGR suckling piglets.

METHODS

Sixteen IUGR and eight normal birth weight (NBW) neonatal male piglets were used in this study. From d 3 to d 24, in addition to drinking milk, the eight NBW piglets (NBW-CON group, n = 8) and eight IUGR piglets (IUGR-CON group, n = 8) were given 10 mL sterile saline once a day, while the remaining IUGR piglets (IUGR-CB group, n = 8) were orally administered C. butyricum at a dose of 2 × 10 colony-forming units (CFU)/kg body weight (suspended in 10 mL sterile saline) at the same frequency.

RESULTS

The IUGR-CON piglets exhibited restricted growth, impaired hepatic morphology, disordered lipid metabolism, increased abundance of opportunistic pathogens and altered ileum and liver bile acid (BA) profiles. However, C. butyricum supplementation reshaped the gut microbiota of the IUGR-CB piglets, characterized by a decreased abundance of opportunistic pathogens in the ileum, including Streptococcus and Enterococcus. The decrease in these bile salt hydrolase (BSH)-producing microbes increased the content of conjugated BAs, which could be transported to the liver and function as signaling molecules to activate liver X receptor α (LXRα) and farnesoid X receptor (FXR). This activation effectively accelerated the synthesis and oxidation of fatty acids and down-regulated the total cholesterol level by decreasing the synthesis and promoting the efflux of cholesterol. As a result, the growth performance and morphological structure of the liver improved in the IUGR piglets.

CONCLUSION

These results indicate that C. butyricum supplementation in IUGR suckling piglets could decrease the abundance of BSH-producing microbes (Streptococcus and Enterococcus). This decrease altered the ileum and liver BA profiles and consequently activated the expression of hepatic LXRα and FXR. The activation of these two signaling molecules could effectively normalize the lipid metabolism and improve the growth performance of IUGR suckling piglets.

摘要

背景

宫内生长受限(IUGR)可导致婴儿脂质紊乱,并对其生长发育产生长期不良影响。丁酸梭菌作为一种新兴的益生菌,据报道可有效减轻脂质代谢功能障碍。因此,本研究的目的是探讨补充丁酸梭菌对IUGR哺乳仔猪肝脏脂质紊乱的影响。

方法

本研究使用了16头IUGR新生雄性仔猪和8头正常出生体重(NBW)的新生雄性仔猪。从第3天到第24天,除了饮用牛奶外,8头NBW仔猪(NBW-CON组,n = 8)和8头IUGR仔猪(IUGR-CON组,n = 8)每天给予10 mL无菌生理盐水,而其余的IUGR仔猪(IUGR-CB组,n = 8)以2×10菌落形成单位(CFU)/千克体重的剂量口服丁酸梭菌(悬浮于10 mL无菌生理盐水中),给药频率相同。

结果

IUGR-CON组仔猪生长受限,肝脏形态受损,脂质代谢紊乱,机会性致病菌丰度增加,回肠和肝脏胆汁酸(BA)谱改变。然而,补充丁酸梭菌重塑了IUGR-CB组仔猪的肠道微生物群,其特征是回肠中机会性致病菌(包括链球菌和肠球菌)的丰度降低。这些产生胆汁盐水解酶(BSH)的微生物数量减少,增加了结合型胆汁酸的含量,后者可转运至肝脏并作为信号分子激活肝脏X受体α(LXRα)和法尼醇X受体(FXR)。这种激活有效地加速了脂肪酸的合成和氧化,并通过减少胆固醇的合成和促进胆固醇的流出下调了总胆固醇水平。结果,IUGR仔猪的生长性能和肝脏形态结构得到改善。

结论

这些结果表明,在IUGR哺乳仔猪中补充丁酸梭菌可降低产生BSH的微生物(链球菌和肠球菌)的丰度。这种降低改变了回肠和肝脏的BA谱,从而激活了肝脏LXRα和FXR的表达。这两种信号分子的激活可有效使脂质代谢正常化,并改善IUGR哺乳仔猪的生长性能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/914f/10009951/ad0081659086/40104_2023_828_Fig1_HTML.jpg

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