Skip to main content

Advertisement

SpringerLink
Log in

Gut Lactobacillus and Probiotics Lactobacillus lactis/rhamnosis Ameliorate Liver Fibrosis in Prevention and Treatment

  • Microbial Pathogenesis and Host-Microbe Interaction
  • Published:
Journal of Microbiology Aims and scope Submit manuscript

Abstract

The progression and exacerbation of liver fibrosis are closely related to the gut microbiome. It is hypothesized that some probiotics may slow the progression of liver fibrosis. In human stool analysis [healthy group (n = 44) and cirrhosis group (n = 18)], difference in Lactobacillus genus between healthy group and cirrhosis group was observed. Based on human data, preventive and therapeutic effect of probiotics Lactobacillus lactis and L. rhamnosus was evaluated by using four mice fibrosis models. L. lactis and L. rhamnosus were supplied to 3,5-diethoxycarbonyl-1,4-dihydrocollidine or carbon tetrachloride-induced liver fibrosis C57BL/6 mouse model. Serum biochemical measurements, tissue staining, and mRNA expression in the liver were evaluated. The microbiome was analyzed in mouse cecal contents. In the mouse model, the effects of Lactobacillus in preventing and treating liver fibrosis were different for each microbe species. In case of L. lactis, all models showed preventive and therapeutic effects against liver fibrosis. In microbiome analysis in mouse models administered Lactobacillus, migration and changes in the ratio and composition of the gut microbial community were confirmed. L. lactis and L. rhamnosus showed preventive and therapeutic effects on the progression of liver fibrosis, suggesting that Lactobacillus intake may be a useful strategy for prevention and treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

Data available within the article or its supplementary materials.

References

  • Acharya, C., & Bajaj, J. S. (2019). Altered microbiome in patients with cirrhosis and complications. Clinical Gastroenterology and Hepatology, 17, 307–321.

    Article  PubMed  Google Scholar 

  • Arroyo, V., Moreau, R., Kamath, P. S., Jalan, R., Gines, P., Nevens, F., Fernandez, J., To, U., Garcia-Tsao, G., & Schnabl, B. (2016). Acute-on-chronic liver failure in cirrhosis. Nature Reviews Disease Primers, 2, 16041.

    Article  PubMed  Google Scholar 

  • Azad, M. A. K., Sarker, M., Li, T., & Yin, J. (2018). Probiotic species in the modulation of gut microbiota: An overview. BioMed Research International, 2018, 9478630.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bajaj, J. S., Heuman, D. M., Hylemon, P. B., Sanyal, A. J., Puri, P., Sterling, R. K., Luketic, V., Stravitz, R. T., Siddiqui, M. S., Fuchs, M., Thacker, L. R., Wade, J. B., Daita, K., Sistrun, S., White, M. B., Noble, N. A., Thorpe, C., Kakiyama, G., Pandak, W. M., … Gillevet, P. M. (2014). Randomised clinical trial: Lactobacillus gg modulates gut microbiome, metabolome and endotoxemia in patients with cirrhosis. Alimentary Pharmacology & Therapeutics, 39, 1113–1125.

    Article  CAS  Google Scholar 

  • Bataller, R., & Brenner, D. A. (2005). Liver fibrosis. Journal of Clinical Investigation, 115, 209–218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Belkaid, Y., & Hand, T. W. (2014). Role of the microbiota in immunity and inflammation. Cell, 157, 121–141.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carroll, I. M., Andrus, J. M., Bruno-Barcena, J. M., Klaenhammer, T. R., Hassan, H. M., & Threadgill, D. S. (2007). Anti-inflammatory properties of Lactobacillusgasseri expressing manganese superoxide dismutase using the interleukin 10-deficient mouse model of colitis. American Journal of Physiology-Gastrointestinal and Liver Physiology, 293, G729-738.

    Article  CAS  PubMed  Google Scholar 

  • Dong, S., Chen, Q. L., Song, Y. N., Sun, Y., Wei, B., Li, X. Y., Hu, Y. Y., Liu, P., & Su, S. B. (2016). Mechanisms of ccl4-induced liver fibrosis with combined transcriptomic and proteomic analysis. The Journal of Toxicological Sciences, 41, 561–572.

    Article  CAS  PubMed  Google Scholar 

  • Edgar, R. C. (2010). Search and clustering orders of magnitude faster than blast. Bioinformatics, 26, 2460–2461.

    Article  CAS  PubMed  Google Scholar 

  • Famouri, F., Shariat, Z., Hashemipour, M., Keikha, M., & Kelishadi, R. (2017). Effects of probiotics on nonalcoholic fatty liver disease in obese children and adolescents. Journal of Pediatric Gastroenterology and Nutrition, 64, 413–417.

    Article  CAS  PubMed  Google Scholar 

  • Fukui, H. (2019). Role of gut dysbiosis in liver diseases: What have we learned so far? Diseases, 7, 58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghiassi-Nejad, Z., & Friedman, S. L. (2008). Advances in antifibrotic therapy. Expert Review of Gastroenterology & Hepatology, 2, 803–816.

    Article  Google Scholar 

  • Hemarajata, P., & Versalovic, J. (2013). Effects of probiotics on gut microbiota: Mechanisms of intestinal immunomodulation and neuromodulation. Therapeutic Advances in Gastroenterology, 6, 39–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang, C. H., Li, S. W., Huang, L., & Watanabe, K. (2018). Identification and classification for the Lactobacilluscasei group. Frontiers in Microbiology, 9, 1974.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kanmani, P., & Kim, H. (2022). Probiotics counteract the expression of hepatic profibrotic genes via the attenuation of tgf-beta/smad signaling and autophagy in hepatic stellate cells. PLoS ONE, 17, e0262767.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim, S. K., Guevarra, R. B., Kim, Y. T., Kwon, J., Kim, H., Cho, J. H., Kim, H. B., & Lee, J. H. (2019). Role of probiotics in human gut microbiome-associated diseases. Journal of Microbiology and Biotechnology, 29, 1335–1340.

    Article  PubMed  Google Scholar 

  • Lee, N. Y., Joung, H. C., Kim, B. K., Kim, B. Y., Park, T. S., & Suk, K. T. (2020a). Lactobacillus lactis ckdb001 ameliorate progression of nonalcoholic fatty liver disease through of gut microbiome: Addendum. Gut Microbes, 12, 1829449.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee, N. Y., Yoon, S. J., Han, D. H., Gupta, H., Youn, G. S., Shin, M. J., Ham, Y. L., Kwak, M. J., Kim, B. Y., Yu, J. S., Lee, D. Y., Park, T. S., Park, S. H., Kim, B. K., Joung, H. C., Choi, I. S., Hong, J. T., Kim, D. J., Han, S. H., & Suk, K. T. (2020b). Lactobacillus and pediococcus ameliorate progression of non-alcoholic fatty liver disease through modulation of the gut microbiome. Gut Microbes, 11, 882–899.

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu, Y., Chen, K., Li, F., Gu, Z., Liu, Q., He, L., Shao, T., Song, Q., Zhu, F., Zhang, L., Jiang, M., Zhou, Y., Barve, S., Zhang, X., McClain, C. J., & Feng, W. (2020). Probiotic Lactobacillusrhamnosus gg prevents liver fibrosis through inhibiting hepatic bile acid synthesis and enhancing bile acid excretion in mice. Hepatology, 71, 2050–2066.

    Article  CAS  PubMed  Google Scholar 

  • Markowiak, P., & Slizewska, K. (2017). Effects of probiotics, prebiotics, and synbiotics on human health. Nutrients, 9, 1–30.

    Article  Google Scholar 

  • Marotta, F., Barreto, R., Wu, C. C., Naito, Y., Gelosa, F., Lorenzetti, A., Yoshioka, M., & Fesce, E. (2005). Experimental acute alcohol pancreatitis-related liver damage and endotoxemia: Synbiotics but not metronidazole have a protective effect. Chinese Journal of Digestive Diseases, 6, 193–197.

    Article  CAS  PubMed  Google Scholar 

  • Mulaw, G., SisayTessema, T., Muleta, D., & Tesfaye, A. (2019). In vitro evaluation of probiotic properties of lactic acid bacteria isolated from some traditionally fermented Ethiopian food products. International Journal of Microbiology, 2019, 7179514.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ortega, M. A., Fraile-Martinez, O., Naya, I., Garcia-Honduvilla, N., Alvarez-Mon, M., Bujan, J., Asunsolo, A., & de la Torre, B. (2020). Type 2 diabetes mellitus associated with obesity (diabesity). The central role of gut microbiota and its translational applications. Nutrients, 12, 2749.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pan, F., Zhang, L., Li, M., Hu, Y., Zeng, B., Yuan, H., Zhao, L., & Zhang, C. (2018). Predominant gut lactobacillus murinus strain mediates anti-inflammaging effects in calorie-restricted mice. Microbiome., 6, 54.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pose, E., Sancho-Bru, P., & Coll, M. (2019). 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet: A rodent model in cholestasis research. Methods in Molecular Biology, 1981, 249–257.

    Article  CAS  PubMed  Google Scholar 

  • Ray, K. (2017). Alcoholic liver disease: Gut-liver axis: Ppis, enterococcus and promotion of alcoholic liver disease. Nature Reviews Gastroenterology & Hepatology, 14, 689.

    Article  Google Scholar 

  • Schnabl, B., & Brenner, D. A. (2014). Interactions between the intestinal microbiome and liver diseases. Gastroenterology, 146, 1513–1524.

    Article  CAS  PubMed  Google Scholar 

  • Schuppan, D., & Afdhal, N. H. (2008). Liver cirrhosis. The Lancet, 371, 838–851.

    Article  CAS  Google Scholar 

  • Segawa, S., Wakita, Y., Hirata, H., & Watari, J. (2008). Oral administration of heat-killed lactobacillus brevis sbc8803 ameliorates alcoholic liver disease in ethanol-containing diet-fed c57bl/6n mice. International Journal of Food Microbiology, 128, 371–377.

    Article  CAS  PubMed  Google Scholar 

  • Sharma, V., Garg, S., & Aggarwal, S. (2013). Probiotics and liver disease. The Permanente Journal, 17, 62–67.

    Article  PubMed  PubMed Central  Google Scholar 

  • Shi, D., Lv, L., Fang, D., Wu, W., Hu, C., Xu, L., Chen, Y., Guo, J., Hu, X., Li, A., Guo, F., Ye, J., Li, Y., Andayani, D., & Li, L. (2017). Administration of Lactobacillus salivarius li01 or Pediococcus pentosaceus li05 prevents ccl4-induced liver cirrhosis by protecting the intestinal barrier in rats. Scientific Reports, 7, 6927.

    Article  PubMed  PubMed Central  Google Scholar 

  • Trautwein, C., Friedman, S. L., Schuppan, D., & Pinzani, M. (2015). Hepatic fibrosis: Concept to treatment. Journal of Hepatology, 62, S15-24.

    Article  CAS  PubMed  Google Scholar 

  • Turnbaugh, P. J., & Stintzi, A. (2011). Human health and disease in a microbial world. Frontiers in Microbiology, 2, 190.

    Article  PubMed  PubMed Central  Google Scholar 

  • Walker, A. W., & Lawley, T. D. (2013). Therapeutic modulation of intestinal dysbiosis. Pharmacological Research, 69, 75–86.

    Article  CAS  PubMed  Google Scholar 

  • Wang, H., Zhou, C., Huang, J., Kuai, X., & Shao, X. (2020). The potential therapeutic role of Lactobacillusreuteri for treatment of inflammatory bowel disease. American Journal of Translational Research, 12, 1569–1583.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wiegand, J., & Berg, T. (2013). The etiology, diagnosis and prevention of liver cirrhosis: Part 1 of a series on liver cirrhosis. Deutsches Ärzteblatt International, 110, 85–91.

    PubMed  PubMed Central  Google Scholar 

  • Wynn, T. A. (2008). Cellular and molecular mechanisms of fibrosis. Journal of Pathology, 214, 199–210.

    Article  CAS  PubMed  Google Scholar 

  • Wynn, T. A., & Ramalingam, T. R. (2012). Mechanisms of fibrosis: Therapeutic translation for fibrotic disease. Nature Medicine, 18, 1028–1040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xie, J. T., Shao, Z. H., Vanden Hoek, T. L., Chang, W. T., Li, J., Mehendale, S., Wang, C. Z., Hsu, C. W., Becker, L. B., Yin, J. J., & Yuan, C. S. (2006). Antioxidant effects of ginsenoside re in cardiomyocytes. European Journal of Pharmacology, 532, 201–207.

    Article  CAS  PubMed  Google Scholar 

  • Yanguas, S. C., Cogliati, B., Willebrords, J., Maes, M., Colle, I., van den Bossche, B., de Oliveira, C., Andraus, W., Alves, V. A. F., Leclercq, I., & Vinken, M. (2016). Experimental models of liver fibrosis. Archives of Toxicology, 90, 1025–1048.

    Article  CAS  PubMed  Google Scholar 

  • Yoon, S. H., Ha, S. M., Kwon, S., Lim, J., Kim, Y., Seo, H., & Chun, J. (2017). Introducing ezbiocloud: A taxonomically united database of 16s rrna gene sequences and whole-genome assemblies. International Journal of Systematic and Evolutionary Microbiology, 67, 1613–1617.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, Y. J., Li, S., Gan, R. Y., Zhou, T., Xu, D. P., & Li, H. B. (2015). Impacts of gut bacteria on human health and diseases. International Journal of Molecular Sciences, 16, 7493–7519.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This research was supported by Hallym University Research Fund, Korea National Research Foundation (2020R1A6A1A03043026, and 2021M3A9I4021433), Bio Industrial Technology Development Program (20018494) funded by the Ministry of Trade, Industry and Energy (MOTIE, Korea), and the Promotion of Innovative Businesses for Regulation-Free Special Zones funded by the Ministry of SMEs and Startups (MSS, Korea) (P0020622).

Author information

Author notes

  1. Sung Min Won and Sang Jun Yoon contributed equally to this work.

Authors and Affiliations

  1. Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, 24252, Republic of Korea

    Sung Min Won, Na Young Lee, Ki-Kwang Oh, Haripriya Gupta, Satya Priya Sharma, Jin Ju Jeong, Raja Ganesan, Sang Jun Yoon, Dong Joon Kim & Ki Tae Suk

  2. Chong Kun Dang Bio Research Institute, Ansan, Republic of Korea

    Kyung Hwan Kim, Byoung Kook Kim & Hyun Chae Joung

  3. Department of Pathology, Hallym University College of Medicine, Chuncheon, 24252, Republic of Korea

    Sang Hak Han

Authors
  1. Sung Min Won
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Na Young Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ki-Kwang Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Haripriya Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Satya Priya Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kyung Hwan Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Byoung Kook Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hyun Chae Joung
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jin Ju Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Raja Ganesan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sang Hak Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sang Jun Yoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Dong Joon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Ki Tae Suk
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SMW, NYL, and SKK: analysis and interpretation of the data, collection and assembly of data, drafting of the article. SMW and KTS: conception and design, critical revision of the article for important intellectual content, final approval of the article. KKO, HG, SPS, KHK, BKK, HCJ, JJJ, RG, SHH, SJY, and DJK: critical revision of the article for important intellectual content and provision of study materials.

Corresponding author

Correspondence to Ki Tae Suk.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest, including relevant financial interests, activities, relationships, affiliations, and any other conflict of interest as explicitly and implicitly expressed in the Editorial Policies for Authors.

Ethical approval

This study was controlled in accordance with ethical guidelines from the 1975 Helsinki Declaration as reflected by prior approval by the institutional review notice for human research in the hospital participating in the trial (2016-134). Basic information has been registered on ClinicalTrials.gov for registration in the public trial registry (NCT04339725). Informed consent for enrollment was received from each participant. This experiment was designed by selecting a candidate for the treatment of liver disease among the probiotics that approved by Ministry of Food and Drug Safety, Korean. All the procedures were licensed by the Institutional Animal Care and Use Committee of the College of Medicine, Hallym University R1(2019-04).

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 733 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Won, S.M., Lee, N.Y., Oh, KK. et al. Gut Lactobacillus and Probiotics Lactobacillus lactis/rhamnosis Ameliorate Liver Fibrosis in Prevention and Treatment. J Microbiol. 61, 245–257 (2023). https://doi.org/10.1007/s12275-023-00014-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12275-023-00014-y

Keywords

Search

Navigation