Full Text:   <423>

Summary:  <216>

Suppl. Mater.: 

CLC number: 

On-line Access: 2023-08-08

Received: 2022-08-31

Revision Accepted: 2023-03-07

Crosschecked: 2023-08-08

Cited: 0

Clicked: 642

Citations:  Bibtex RefMan EndNote GB/T7714


Xianghua YAN


-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2023 Vol.24 No.8 P.734-748


Lactobacillus gasseri LA39 promotes hepatic primary bile acid biosynthesis and intestinal secondary bile acid biotransformation

Author(s):  Jun HU, Qiliang HOU, Wenyong ZHENG, Tao YANG, Xianghua YAN

Affiliation(s):  National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Frontiers Science Center for Animal Breeding and Sustainable Production, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan 430070, China; more

Corresponding email(s):   xhyan@mail.hzau.edu.cn

Key Words:  Lactobacillus gasseri LA39, Liver, Isobaric tags for relative and absolute quantitation (iTRAQ), Bile acid, Germ-free mice

Jun HU, Qiliang HOU, Wenyong ZHENG, Tao YANG, Xianghua YAN. Lactobacillus gasseri LA39 promotes hepatic primary bile acid biosynthesis and intestinal secondary bile acid biotransformation[J]. Journal of Zhejiang University Science B, 2023, 24(8): 734-748.

@article{title="Lactobacillus gasseri LA39 promotes hepatic primary bile acid biosynthesis and intestinal secondary bile acid biotransformation",
author="Jun HU, Qiliang HOU, Wenyong ZHENG, Tao YANG, Xianghua YAN",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Lactobacillus gasseri LA39 promotes hepatic primary bile acid biosynthesis and intestinal secondary bile acid biotransformation
%A Jun HU
%A Qiliang HOU
%A Wenyong ZHENG
%A Xianghua YAN
%J Journal of Zhejiang University SCIENCE B
%V 24
%N 8
%P 734-748
%@ 1673-1581
%D 2023
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2200439

T1 - Lactobacillus gasseri LA39 promotes hepatic primary bile acid biosynthesis and intestinal secondary bile acid biotransformation
A1 - Jun HU
A1 - Qiliang HOU
A1 - Wenyong ZHENG
A1 - Tao YANG
A1 - Xianghua YAN
J0 - Journal of Zhejiang University Science B
VL - 24
IS - 8
SP - 734
EP - 748
%@ 1673-1581
Y1 - 2023
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2200439

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.


胡军1,2,3, 侯奇良1,2,3, 郑文涌1,2,3, 杨涛1,2,3, 晏向华1,2,3
1农业微生物资源发掘与利用全国重点实验室, 湖北洪山实验室, 动物育种与健康养殖前沿科学中心,动物科学技术学院, 华中农业大学, 中国武汉市, 430070
2生猪健康养殖协同创新中心, 中国武汉市, 430070
3生猪精准饲养与饲料安全技术湖北省工程实验室, 中国武汉市, 430070
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。


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Al-AsmakhM, ZadjaliF, 2015. Use of germ-free animal models in microbiota-related research. J Microbiol Biotechnol, 25(10):1583-1588.

[2]BajajJS, NgSC, SchnablB, 2022. Promises of microbiome-based therapies. J Hepatol, 76(6):1379-1391.

[3]BernardeauM, GuguenM, VernouxJP, 2006. Beneficial lactobacilli in food and feed: long-term use, biodiversity and proposals for specific and realistic safety assessments. FEMS Microbiol Rev, 30(4):487-513.

[4]BhattaraiY, KashyapPC, 2016. Germ-free mice model for studying host-microbial interactions. In: Proetzel G, Wiles M (Eds.), Mouse Models for Drug Discovery. Humana Press, New York, p.123-135.

[5]BrandlK, KumarV, EckmannL, 2017. Gut-liver axis at the frontier of host-microbial interactions. Am J Physiol Gastrointest Liver Physiol, 312(5):G413-G419.

[6]BuffieCG, BucciV, SteinRR, et al., 2015. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature, 517(7533):205-208.

[7]CaiJ, SunLL, GonzalezFJ, 2022. Gut microbiota-derived bile acids in intestinal immunity, inflammation, and tumorigenesis. Cell Host Microbe, 30(3):289-300.

[8]de BoeverP, WoutersR, VerschaeveL, et al., 2000. Protective effect of the bile salt hydrolase-active Lactobacillus reuteri against bile salt cytotoxicity. Appl Microbiol Biotechnol, 53(6):709-714.

[9]DegirolamoC, RainaldiS, BovengaF, et al., 2014. Microbiota modification with probiotics induces hepatic bile acid synthesis via downregulation of the Fxr-Fgf15 axis in mice. Cell Rep, 7(1):12-18.

[10]DeSouzaL, DiehlG, RodriguesMJ, et al., 2005. Search for cancer markers from endometrial tissues using differentially labeled tags iTRAQ and cICAT with multidimensional liquid chromatography and tandem mass spectrometry. J Proteome Res, 4(2):377-386.

[11]FoleyMH, O'FlahertyS, AllenG, et al., 2021. Lactobacillus bile salt hydrolase substrate specificity governs bacterial fitness and host colonization. Proc Natl Acad Sci USA, 118(6):e2017709118.

[12]GadaletaRM, van ErpecumKJ, OldenburgB, et al., 2011. Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease. Gut, 60(4):463-472.

[13]GroverM, KashyapPC, 2014. Germ-free mice as a model to study effect of gut microbiota on host physiology. Neurogastroenterol Motil, 26(6):745-748.

[14]GuziorDV, QuinnRA, 2021. Review: microbial transformations of human bile acids. Microbiome, 9:140.

[15]HuJ, NieYF, ChenSF, et al., 2017. Leucine reduces reactive oxygen species levels via an energy metabolism switch by activation of the mTOR-HIF-‍‍1α pathway in porcine intestinal epithelial cells. Int J Biochem Cell Biol, 89:42-56.

[16]HuJ, MaLB, ZhengWY, et al., 2018a. Lactobacillus gasseri LA39 activates the oxidative phosphorylation pathway in porcine intestinal epithelial cells. Front Microbiol, 9:3025.

[17]HuJ, MaLB, NieYF, et al., 2018b. A microbiota-derived bacteriocin targets the host to confer diarrhea resistance in early-weaned piglets. Cell Host Microbe, 24(6):817-832.e8.

[18]HuangHY, ZhangWT, JiangWY, et al., 2015. RhoGDIβ inhibits bone morphogenetic protein 4 (BMP4)‍-induced adipocyte lineage commitment and favors smooth muscle-like cell differentiation. J Biol Chem, 290(17):‍11119-11129.

[19]KawaiY, SaitoT, TobaT, et al., 1994. Isolation and characterization of a highly hydrophobic new bacteriocin (gassericin A) from Lactobacillus gasseri LA39. Biosci Biotechnol Biochem, 58(7):1218-1221.

[20]KawaiY, IshiiY, UemuraK, et al., 2001. Lactobacillus reuteri LA6 and Lactobacillus gasseri LA39 isolated from faeces of the same human infant produce identical cyclic bacteriocin. Food Microbiol, 18(4):407-415.

[21]KleerebezemM, VaughanEE, 2009. Probiotic and gut lactobacilli and bifidobacteria: molecular approaches to study diversity and activity. Annu Rev Microbiol, 63:269-290.

[22]KusadaH, MorinagaK, TamakiH, 2021. Identification of bile salt hydrolase and bile salt resistance in a probiotic bacterium Lactobacillus gasseri JCM1131T. Microorganisms, 9(5):1011.

[23]LebeerS, VanderleydenJ, de KeersmaeckerSCJ, 2008. Genes and molecules of lactobacilli supporting probiotic action. Microbiol Mol Biol Rev, 72(4):728-764.

[24]LemonKP, ArmitageGC, RelmanDA, et al., 2012. Microbiota-targeted therapies: an ecological perspective. Sci Transl Med, 4(137):137rv5.

[25]LiF, JiangCT, KrauszKW, et al., 2013. Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity. Nat Commun, 4:2384.

[26]LiuYH, ChenKF, LiFY, et al., 2020. Probiotic Lactobacillus rhamnosus GG prevents liver fibrosis through inhibiting hepatic bile acid synthesis and enhancing bile acid excretion in mice. Hepatology, 71(6):2050-2066.

[27]LiuZJ, XuC, TianR, et al., 2021. Screening beneficial bacteriostatic lactic acid bacteria in the intestine and studies of bacteriostatic substances. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 22(7):533-547.

[28]LiuZM, ZhangZF, HuangM, et al., 2018. Taurocholic acid is an active promoting factor, not just a biomarker of progression of liver cirrhosis: evidence from a human metabolomic study and in vitro experiments. BMC Gastroenterol, 18:112.

[29]MarchesiJR, AdamsDH, FavaF, et al., 2016. The gut microbiota and host health: a new clinical frontier. Gut, 65(2):330-339.

[30]MaslennikovR, IvashkinV, EfremovaI, et al., 2021. Probiotics in hepatology: an update. World J Hepatol, 13(9):‍1154-1166.

[31]NatividadJMM, VerduEF, 2013. Modulation of intestinal barrier by intestinal microbiota: pathological and therapeutic implications. Pharmacol Res, 69(1):42-51.

[32]NieYF, HuJ, YanXH, 2015. Cross-talk between bile acids and intestinal microbiota in host metabolism and health. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 16(6):‍436-446.

[33]NieYF, HuJ, HouQL, et al., 2019. Lactobacillus frumenti improves antioxidant capacity via nitric oxide synthase 1 in intestinal epithelial cells. FASEB J, 33(10):‍10705-10716.

[34]OgilvieLA, JonesBV, 2012. Dysbiosis modulates capacity for bile acid modification in the gut microbiomes of patients with inflammatory bowel disease: a mechanism and marker of disease? Gut, 61(11):1642-1643.

[35]RamakrishnaBS, 2013. Role of the gut microbiota in human nutrition and metabolism. J Gastroenterol Hepatol, 28(S4):9-17.

[36]RingseisR, GessnerDK, EderK, 2020. The gut‒liver axis in the control of energy metabolism and food intake in animals. Annu Rev Anim Biosci, 8:295-319.

[37]RooksMG, GarrettWS, 2016. Gut microbiota, metabolites and host immunity. Nat Rev Immunol, 16(6):341-352.

[38]ScottA, 2017. Gut‍‒‍liver axis: menace in the microbiota. Nature, 551(7681):S94-S95.

[39]SelleK, KlaenhammerTR, 2013. Genomic and phenotypic evidence for probiotic influences of Lactobacillus gasseri on human health. FEMS Microbiol Rev, 37(6):915-935.

[40]SilveiraMAD, BilodeauS, GretenTF, et al., 2022. The gut‒liver axis: host microbiota interactions shape hepatocarcinogenesis. Trends Cancer, 8(7):583-597.

[41]SommerF, BäckhedF, 2013. The gut microbiota—masters of host development and physiology. Nat Rev Microbiol, 11(4):227-238.

[42]ThomsonAW, KnollePA, 2010. Antigen-presenting cell function in the tolerogenic liver environment. Nat Rev Immunol, 10(11):753-766.

[43]TilgH, AdolphTE, TraunerM, 2022. Gut-liver axis: pathophysiological concepts and clinical implications. Cell Metab, 34(11):1700-1718.

[44]TremaroliV, BäckhedF, 2012. Functional interactions between the gut microbiota and host metabolism. Nature, 489(7415):242-249.

[45]TreumannA, ThiedeB, 2010. Isobaric protein and peptide quantification: perspectives and issues. Expert Rev Proteomics, 7(5):647-653.

[46]TripathiA, DebeliusJ, BrennerDA, et al., 2018. The gut‒liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol, 15(7):397-411.

[47]UbedaC, PamerEG, 2012. Antibiotics, microbiota, and immune defense. Trends Immunol, 33(9):459-466.

[48]van BaarlenP, WellsJM, KleerebezemM, 2013. Regulation of intestinal homeostasis and immunity with probiotic lactobacilli. Trends Immunol, 34(5):208-215.

[49]WahlströmA, SayinSI, MarschallHU, et al., 2016. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab, 24(1):41-50.

[50]WongWY, ChanBD, ShamTT, et al., 2022. Lactobacillus casei strain Shirota ameliorates dextran sulfate sodium-induced colitis in mice by increasing taurine-conjugated bile acids and inhibiting NF‍-‍κB signaling via stabilization of IκBα. Front Nutr, 9:816836.

[51]WrightMH, 2018. Chemical proteomics of host-microbe interactions. Proteomics, 18(18):1700333.

[52]XieZY, ZhangLJ, ChenEM, et al., 2021. Targeted metabolomics analysis of bile acids in patients with idiosyncratic drug-induced liver injury. Metabolites, 11(12):852.

[53]YanZZ, ChenBX, YangYQ, et al., 2022. Multi-omics analyses of airway host-microbe interactions in chronic obstructive pulmonary disease identify potential therapeutic interventions. Nat Microbiol, 7(9):1361-1375.

[54]YiP, LiLJ, 2012. The germfree murine animal: an important animal model for research on the relationship between gut microbiota and the host. Vet Microbiol, 157(1-2):1-7.

[55]ZhangQQ, HuangWQ, GaoYQ, et al., 2018. Metabolomics reveals the efficacy of caspase inhibition for saikosaponin D-induced hepatotoxicity. Front Pharmacol, 9:732.

[56]ZhangYL, LiZJ, GouHZ, et al., 2022. The gut microbiota-bile acid axis: a potential therapeutic target for liver fibrosis. Front Cell Infect Microbiol, 12:945368.

[57]ZhouWY, SailaniMR, ContrepoisK, et al., 2019. Longitudinal multi-omics of host-microbe dynamics in prediabetes. Nature, 569(7758):663-671.

[58]ZhuMM, DaiSJ, McClungS, et al., 2009. Functional differentiation of Brassica napus guard cells and mesophyll cells revealed by comparative proteomics. Mol Cell Proteomics, 8(4):752-766.

[59]ZouedA, ZhangHL, ZhangT, et al., 2021. Proteomic analysis of the host-pathogen interface in experimental cholera. Nat Chem Biol, 17(11):1199-1208.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE