Probiotic Lactobacillus casei Shirota prevents acute liver injury by reshaping the gut microbiota to alleviate excessive inflammation and metabolic disorders.

Ren Yan, Kaicen Wang, Qiangqiang Wang, Huiyong Jiang, Yingfeng Lu, Xiaoxiao Chen, Hua Zhang, Xiaoling Su, Yiling Du, Lifeng Chen, Lanjuan Li, Longxian Lv
Author Information
  1. Ren Yan: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
  2. Kaicen Wang: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
  3. Qiangqiang Wang: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
  4. Huiyong Jiang: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
  5. Yingfeng Lu: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
  6. Xiaoxiao Chen: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
  7. Hua Zhang: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
  8. Xiaoling Su: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
  9. Yiling Du: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
  10. Lifeng Chen: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
  11. Lanjuan Li: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
  12. Longxian Lv: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China. ORCID

Abstract

Millions of people die from liver diseases annually, and liver failure is one of the three major outcomes of liver disease. The gut microbiota plays a crucial role in liver diseases. This study aimed to explore the effects of Lactobacillus casei strain Shirota (LcS), a probiotics used widely around the world, on acute liver injury (ALI), as well as the underlying mechanism. Sprague Dawley rats were intragastrically administered LcS suspensions or placebo once daily for 7 days before induction of ALI by intraperitoneal injection of D-galactosamine (D-GalN). Histopathological examination and assessments of liver biochemical markers, inflammatory cytokines, and the gut microbiota, metabolome and transcriptome were conducted. Our results showed that pretreatment with LcS reduced hepatic and intestinal damage and reduced the elevation of serum gamma-glutamyltranspeptidase (GGT), total bile acids, IL-5, IL-10, G-CSF and RANTES. The analysis of the gut microbiota, metabolome and transcriptome showed that LcS lowered the ratio of Firmicutes to Bacteroidetes; reduced the enrichment of metabolites such as chenodeoxycholic acid, deoxycholic acid, lithocholic acid, d-talose and N-acetyl-glucosamine, reduce the depletion of d-glucose and l-methionine; and alleviated the downregulation of retinol metabolism and PPAR signalling and the upregulation of the pyruvate metabolism pathway in the liver. These results indicate the promising prospect of using LcS for the treatment of liver diseases, particularly ALI.

References

  1. J Neurogastroenterol Motil. 2019 Jan 31;25(1):148-158 [PMID: 30646486]
  2. Clin Exp Allergy. 2008 Aug;38(8):1282-9 [PMID: 18510694]
  3. Scand J Gastroenterol. 2014 May;49(5):552-63 [PMID: 24621348]
  4. Ann Lab Med. 2018 Jan;38(1):71-73 [PMID: 29071824]
  5. Nat Commun. 2019 Apr 3;10(1):1523 [PMID: 30944313]
  6. Cell Metab. 2014 Feb 4;19(2):193-208 [PMID: 24440037]
  7. Curr Opin Cell Biol. 2015 Feb;32:13-20 [PMID: 25460777]
  8. Transl Res. 2019 Apr;206:107-118 [PMID: 30615844]
  9. Benef Microbes. 2017 Oct 13;8(5):697-703 [PMID: 28726510]
  10. Benef Microbes. 2017 Feb 7;8(1):23-29 [PMID: 27903092]
  11. Clin Exp Med. 2017 Aug;17(3):269-280 [PMID: 27655446]
  12. Cell Metab. 2010 Nov 3;12(5):509-20 [PMID: 21035761]
  13. J Mol Biol. 2019 Jul 26;431(16):2932-2945 [PMID: 31132360]
  14. Clin Liver Dis. 2018 Nov;22(4):773-805 [PMID: 30266162]
  15. Front Microbiol. 2019 Jul 31;10:1477 [PMID: 31417501]
  16. Anal Bioanal Chem. 2017 Feb;409(5):1231-1245 [PMID: 27822648]
  17. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4794-9 [PMID: 21383142]
  18. Can J Gastroenterol. 2003 Nov;17(11):655-9 [PMID: 14631461]
  19. EMBO Rep. 2016 Sep;17(9):1292-303 [PMID: 27418314]
  20. Environ Microbiol. 2016 Jul;18(7):2272-86 [PMID: 27243236]
  21. Biosci Microbiota Food Health. 2018;37(1):9-18 [PMID: 29387517]
  22. Endocr Metab Immune Disord Drug Targets. 2019;19(5):549-570 [PMID: 30360751]
  23. Eur J Nutr. 2017 Feb;56(1):45-53 [PMID: 26419583]
  24. Microb Biotechnol. 2020 Nov;13(6):1860-1876 [PMID: 32652882]
  25. Hepatology. 2015 Aug;62(2):635-43 [PMID: 25678132]
  26. Eur J Nutr. 2013 Dec;52(8):1853-63 [PMID: 23307112]
  27. Hepatology. 2020 Jun;71(6):2050-2066 [PMID: 31571251]
  28. Annu Rev Physiol. 2006;68:159-91 [PMID: 16460270]
  29. Gut. 2000 Oct;47(4):553-62 [PMID: 10986217]
  30. Mucosal Immunol. 2017 Jan;10(1):104-116 [PMID: 27118489]
  31. Lancet. 2019 Sep 7;394(10201):869-881 [PMID: 31498101]
  32. Benef Microbes. 2017 Apr 26;8(2):153-162 [PMID: 28443383]
  33. Front Microbiol. 2018 Aug 21;9:1967 [PMID: 30186272]
  34. Curr Opin Gastroenterol. 2014 May;30(3):332-8 [PMID: 24625896]
  35. Arch Surg. 1970 Oct;101(4):478-83 [PMID: 5457245]
  36. Autoimmun Rev. 2017 Sep;16(9):885-896 [PMID: 28698093]
  37. FEMS Microbiol Lett. 2009 Apr;293(2):263-70 [PMID: 19243441]
  38. Cell Metab. 2016 Jul 12;24(1):41-50 [PMID: 27320064]
  39. Gut. 2020 Apr;69(4):665-672 [PMID: 31243055]
  40. Cell Mol Gastroenterol Hepatol. 2019;7(2):275-284 [PMID: 30686780]
  41. J Clin Biochem Nutr. 2018 Nov;63(3):233-237 [PMID: 30487675]
  42. J Cell Physiol. 2019 Mar;234(3):2277-2295 [PMID: 30191985]
  43. Gastroenterology. 2011 Sep;141(3):959-71 [PMID: 21699778]
  44. FASEB J. 2019 Sep;33(9):9706-9730 [PMID: 31237779]
  45. Nat Chem Biol. 2015 Sep;11(9):685-90 [PMID: 26192599]
  46. Appl Microbiol Biotechnol. 2019 Dec;103(23-24):9673-9686 [PMID: 31713675]
  47. Hepatology. 1981 Sep-Oct;1(5):431-5 [PMID: 7308988]
  48. Biomed Pharmacother. 2021 Jan;133:111000 [PMID: 33202285]
  49. World J Gastroenterol. 2016 Jul 14;22(26):5958-70 [PMID: 27468190]
  50. Gastroenterology. 2011 Feb;140(2):638-45 [PMID: 20977905]

MeSH Term

Animals
Gastrointestinal Microbiome
Inflammation
Lacticaseibacillus casei
Liver
Metabolic Diseases
Probiotics
Rats
Rats, Sprague-Dawley

Word Cloud

Created with Highcharts 10.0.0liverLcSgutmicrobiotadiseasesALIreducedacidLactobacilluscaseiShirotaacuteinjurymetabolometranscriptomeresultsshowedmetabolismMillionspeopledieannuallyfailureonethreemajoroutcomesdiseaseplayscrucialrolestudyaimedexploreeffectsstrainprobioticsusedwidelyaroundworldwellunderlyingmechanismSpragueDawleyratsintragastricallyadministeredsuspensionsplacebodaily7 daysinductionintraperitonealinjectionD-galactosamineD-GalNHistopathologicalexaminationassessmentsbiochemicalmarkersinflammatorycytokinesconductedpretreatmenthepaticintestinaldamageelevationserumgamma-glutamyltranspeptidaseGGTtotalbileacidsIL-5IL-10G-CSFRANTESanalysisloweredratioFirmicutesBacteroidetesenrichmentmetaboliteschenodeoxycholicdeoxycholiclithocholicd-taloseN-acetyl-glucosaminereducedepletiond-glucosel-methioninealleviateddownregulationretinolPPARsignallingupregulationpyruvatepathwayindicatepromisingprospectusingtreatmentparticularlyProbioticpreventsreshapingalleviateexcessiveinflammationmetabolicdisorders

Similar Articles

Cited By