Abstract
A growing body of evidence has linked the gut microbiota to liver metabolism. The manipulation of intestinal microflora has been considered as a promising avenue to promote liver health. However, the effects of Lactobacillus gasseri LA39, a potential probiotic, on liver metabolism remain unclear. Accumulating studies have investigated the proteomic profile for mining the host biological events affected by microbes, and used the germ-free (GF) mouse model to evaluate host-microbe interaction. Here, we explored the effects of L. gasseri LA39 gavage on the protein expression profiles of the liver of GF mice. Our results showed that a total of 128 proteins were upregulated, whereas a total of 123 proteins were downregulated by treatment with L. gasseri LA39. Further bioinformatics analyses suggested that the primary bile acid (BA) biosynthesis pathway in the liver was activated by L. gasseri LA39. Three differentially expressed proteins (cytochrome P450 family 27 subfamily A member 1 (CYP27A1), cytochrome P450 family 7 subfamily B member 1 (CYP7B1), and cytochrome P450 family 8 subfamily B member 1 (CYP8B1)) involved in the primary BA biosynthesis pathway were further validated by western blot assay. In addition, targeted metabolomic analyses demonstrated that serum and fecal β-muricholic acid (a primary BA), dehydrolithocholic acid (a secondary BA), and glycolithocholic acid-3-sulfate (a secondary BA) were significantly increased by L. gasseri LA39. Thus, our data revealed that L. gasseri LA39 activates the hepatic primary BA biosynthesis and promotes the intestinal secondary BA biotransformation. Based on these findings, we suggest that L. gasseri LA39 confers an important function in the gut–liver axis through regulating BA metabolism.
摘要
越来越多的证据已将肠道微生物与肝脏代谢联系在一起. 肠道菌群干预已被视为一条有望促进肝脏健康的途径. 然而, 格氏乳酸杆菌LA39(一种潜在的益生菌)对肝脏代谢的影响仍不明确. 大量的研究已通过分析蛋白组图谱来挖掘受微生物影响的宿主生物学事件, 并利用无菌小鼠模型来研究宿主与微生物的互作. 在本研究中, 我们探讨了格氏乳酸杆菌LA39灌服处理对无菌小鼠肝脏蛋白表达图谱的影响. 结果表明, 格氏乳酸杆菌LA39可导致128个肝脏蛋白质的表达上调, 以及123个肝脏蛋白质的表达下调. 进一步的生物信息学分析表明, 格氏乳酸杆菌LA39可激活肝脏中初级胆汁酸的生物合成通路. 蛋白免疫印迹实验进一步验证了参与初级胆汁酸生物合成通路的三个差异表达蛋白(CYP27A1、 CYP7B1和CYP8B1). 此外, 靶向代谢组学分析证明了格氏乳酸杆菌LA39可显著增加血清和粪便中的β-鼠胆酸(一种初级胆汁酸)、 脱氢石胆酸(一种次级胆汁酸)和甘氨石胆酸-3-硫酸盐(一种次级胆汁酸)的含量. 综上所述, 格氏乳酸杆菌LA39可激活肝脏中初级胆汁酸的生物合成, 并促进肠道中次级胆汁酸的生物转化. 这些研究发现暗示了格氏乳酸杆菌LA39通过调控胆汁酸代谢在肠-肝轴中发挥了重要功能.
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Acknowledgments
This work was supported by the National Natural Science Foundation of China (Nos. 31925037, 31730090, and 32102499), the National Postdoctoral Program for Innovative Talents of China (No. BX20190133), the Postdoctoral Science Foundation of China (No. 2019M662671), and the Natural Science Foundation of Hubei Province (Nos. 2022CFB358 and 2021CFA018).
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Jun HU designed the study, conducted the experiments, and wrote the manuscript. Qiliang HOU, Wenyong ZHENG, and Tao YANG conducted the experiments. Xianghua YAN designed the study and wrote the manuscript. All authors have read and approved the final manuscript, and therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
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Jun HU, Qiliang HOU, Wenyong ZHENG, Tao YANG, and Xianghua YAN declare that they have no conflict of interest.
All mice procedures were carried out following the guidelines approved by Institutional Animal Care and Use Committee of Huazhong Agricultural University, Wuhan, China (approval No. HZAUMO-2018-067).
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Table S1; Fig. S1; Data S1
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Hu, J., Hou, Q., Zheng, W. et al. Lactobacillus gasseri LA39 promotes hepatic primary bile acid biosynthesis and intestinal secondary bile acid biotransformation. J. Zhejiang Univ. Sci. B 24, 734–748 (2023). https://doi.org/10.1631/jzus.B2200439
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DOI: https://doi.org/10.1631/jzus.B2200439
Key words
- Lactobacillus gasseri LA39
- Liver
- Isobaric tags for relative and absolute quantitation (iTRAQ)
- Bile acid
- Germ-free mice