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Lactobacillus paracasei R3 Alleviates Tumor Progression in Mice with Colorectal Cancer

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Abstract

Lactobacillus paracasei (L. paracasei), a common probiotic lactobacillus, has important functions in the food industry and human health. However, different strains of L. paracasei inevitably show differences in activity and colonization resistance, leading to differentiation in their functions, as well as their physical or chemical properties. The purpose of this study was to evaluate the characteristics of L. paracasei R3 (L.p R3) isolated from healthy human feces and determine whether the criteria for edible probiotics is met. The hemolysis type, biofilm-forming ability, antibiotic susceptibility, toxicity, and effective activity of L.p R3 were determined by establishing its probiotic activity traits in vitro and in vivo. The results showed that L.p R3 had a moderate biofilm formation ability, was sensitive to 11 antibiotics, was resistant to eight antibiotics, and was not hemolytic. The culture characteristics, morphology, and biochemical responses of the strain were consistent with the seed batch characteristics. In toxicity assays, L.p R3-fed mice showed no abnormalities in body weight, growth, or various organs. Additionally, L.p R3 was found to be effective in the prevention and treatment of colorectal cancer. In conclusion, our results revealed that L.p R3 has potential value as an edible probiotic without toxic side effects and alleviated the tumor progression of colorectal cancer in mice.

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References

  1. World Health Organization & Food and Agriculture Organization of the United Nations (2001) Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. American Córdoba Park Hote, Córdoba

    Google Scholar 

  2. Gupta V, Garg R (2009) Probiotics. Indian J Med Microbiol 27(3):202–209. https://doi.org/10.4103/0255-0857.53201

    Article  CAS  PubMed  Google Scholar 

  3. Stefanovic E, Fitzgerald G, McAuliffe O (2017) Advances in the genomics and metabolomics of dairy lactobacilli: a review. Food Microbiol 61:33–49. https://doi.org/10.1016/j.fm.2016.08.009

    Article  CAS  PubMed  Google Scholar 

  4. Zhao H, Chen X, Zhang L, Meng F, Zhou L, Pang X, Lu Z, Lu Y (2022) Lacticaseibacillus rhamnosus Fmb14 prevents purine induced hyperuricemia and alleviate renal fibrosis through gut-kidney axis. Pharmacol Res 182:106350. https://doi.org/10.1016/j.phrs.2022.106350

    Article  CAS  PubMed  Google Scholar 

  5. De Boeck I, van den Broek MFL, Allonsius CN, Spacova I, Wittouck S, Martens K, Wuyts S, Cauwenberghs E, Jokicevic K, Vandenheuvel D, Eilers T, Lemarcq M, De Rudder C, Thys S, Timmermans JP, Vroegop AV, Verplaetse A, Van de Wiele T, Kiekens F, Hellings PW, Vanderveken OM, Lebeer S (2020) Lactobacilli have a niche in the human nose. Cell Rep 31(8):107674. https://doi.org/10.1016/j.celrep.2020.107674

    Article  CAS  PubMed  Google Scholar 

  6. Jobin C (2018) Precision medicine using microbiota. Science 359(6371):32–34. https://doi.org/10.1126/science.aar2946

    Article  CAS  PubMed  Google Scholar 

  7. Weiss GA, Hennet T (2017) Mechanisms and consequences of intestinal dysbiosis. Cell Mol Life Sci 74(16):2959–2977. https://doi.org/10.1007/s00018-017-2509-x

    Article  CAS  PubMed  Google Scholar 

  8. Gensollen T, Iyer SS, Kasper DL, Blumberg RS (2016) How colonization by microbiota in early life shapes the immune system. Science 352(6285):539–544. https://doi.org/10.1126/science.aad9378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yu LX, Schwabe RF (2017) The gut microbiome and liver cancer: mechanisms and clinical translation. Nat Rev Gastroenterol Hepatol 14(9):527–539. https://doi.org/10.1038/nrgastro.2017.72

    Article  PubMed  PubMed Central  Google Scholar 

  10. Schwabe RF, Greten TF (2020) Gut microbiome in HCC-mechanisms, diagnosis and therapy. J Hepatol 72(2):230–238. https://doi.org/10.1016/j.jhep.2019.08.016

    Article  CAS  PubMed  Google Scholar 

  11. Zitvogel L, Ma Y, Raoult D, Kroemer G, Gajewski TF (2018) The microbiome in cancer immunotherapy: diagnostic tools and therapeutic strategies. Science 359(6382):1366–1370. https://doi.org/10.1126/science.aar6918

    Article  CAS  PubMed  Google Scholar 

  12. Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, Luke JJ, Gajewski TF (2018) The commensal microbiome is associated with anti-pd-1 efficacy in metastatic melanoma patients. Science 359(6371):104–108. https://doi.org/10.1126/science.aao3290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Derosa L, Hellmann MD, Spaziano M, Halpenny D, Fidelle M, Rizvi H, Long N, Plodkowski AJ, Arbour KC, Chaft JE, Rouche JA, Zitvogel L, Zalcman G, Albiges L, Escudier B, Routy B (2018) Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann Oncol 29(6):1437–1444. https://doi.org/10.1093/annonc/mdy103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zhang S, Liang W, Luo L, Sun S, Wang F (2020) The role of t cell trafficking in ctla-4 blockade-induced gut immunopathology. BMC Biol 18(1):29. https://doi.org/10.1186/s12915-020-00765-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Li Q, Li Y, Wang Y, Xu L, Guo Y, Wang Y, Wang L, Guo C (2021) Oral administration of Bifidobacterium breve promotes antitumor efficacy via dendritic cells-derived interleukin 12. Oncoimmunology 10(1):1868122. https://doi.org/10.1080/2162402X.2020.1868122

    Article  PubMed  PubMed Central  Google Scholar 

  16. Heumann A, Assifaoui A, Da Silva BD, Thomas C, Briandet R, Laurent J, Beney L, Lapaquette P, Guzzo J, Rieu A (2020) Intestinal release of biofilm-like microcolonies encased in calcium-pectinate beads increases probiotic properties of Lacticaseibacillus paracasei. NPJ Biofilms Microbiomes 6(1):44. https://doi.org/10.1038/s41522-020-00159-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Poon T, Juana J, Noori D, Jeansen S, Pierucci-Lagha A, Musa-Veloso K (2020) Effects of a fermented dairy drink containing Lacticaseibacillus paracasei subsp. Paracasei CNCM I-1518 (Lactobacillus casei c CNCM I -1518) and the standard yogurt cultures on the incidence, duration, and severity of common infectious diseases: a systematic review and meta-analysis of randomized controlled trials. Nutrients 12(11):3443. https://doi.org/10.3390/nu12113443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dietrich CG, Kottmann T, Alavi M (2014) Commercially available probiotic drinks containing Lactobacillus casei dn-114001 reduce antibiotic-associated diarrhea. World J Gastroenterol 20(42):15837–15844. https://doi.org/10.3748/wjg.v20.i42.15837

    Article  PubMed  PubMed Central  Google Scholar 

  19. Hickson M, D’Souza AL, Muthu N, Rogers TR, Want S, Rajkumar C, Bulpitt CJ (2007) Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. BMJ 335(7610):80. https://doi.org/10.1136/bmj.39231.599815.55

    Article  PubMed  PubMed Central  Google Scholar 

  20. Pan T, Guo HY, Zhang H, Liu AP, Wang XX, Ren FZ (2014) Oral administration of Lactobacillus paracasei alleviates clinical symptoms of colitis induced by dextran sulphate sodium salt in balb/c mice. Benef Microbes 5(3):315–322. https://doi.org/10.3920/BM2013.0041

    Article  CAS  PubMed  Google Scholar 

  21. Shi Y, Meng L, Zhang C, Zhang F, Fang Y (2021) Extracellular vesicles of Lacticaseibacillus paracasei pc-h1 induce colorectal cancer cells apoptosis via PDK1/AKT/BCL-2 signaling pathway. Microb Res 255:126921. https://doi.org/10.1016/j.micres.2021.126921

    Article  CAS  Google Scholar 

  22. Zhang H, Wang Y, Sun J, Guo Z, Guo H, Ren F (2013) Safety evaluation of Lactobacillus paracasei subsp. Paracasei LC-01, a probiotic bacterium. J Microbiol 51(5):633–638. https://doi.org/10.1007/s12275-013-3336-x

    Article  PubMed  Google Scholar 

  23. Huang J, Yang Z, Li Y, Chai X, Liang Y, Lin B, Ye Z, Zhang S, Che Z, Zhang H, Zhang X, Zhang Z, Chen T, Yang W, Zeng J (2021) Lactobacillus paracasei R3 protects against dextran sulfate sodium (DSS)-induced colitis in mice via regulating Th17/Treg cell balance. J Transl Med 19(1):356. https://doi.org/10.1186/s12967-021-02943-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Iseppi R, Messi P, Camellini S, Sabia C (2019) Bacteriocin activity of Lactobacillus brevis and Lactobacillus paracasei ssp paracasei. J Med Microbiol 68(9):1359–1366. https://doi.org/10.1099/jmm.0.001045

    Article  CAS  PubMed  Google Scholar 

  25. Zhang D, Xia J, Xu Y, Gong M, Zhou Y, Xie L, Fang X (2016) Biological features of biofilm-forming ability of Acinetobacter baumannii strains derived from 121 elderly patients with hospital-acquired pneumonia. Clin Exp Med 16(1):73–80. https://doi.org/10.1007/s10238-014-0333-2

    Article  CAS  PubMed  Google Scholar 

  26. Song L, Hobaugh MR, Shustak C, Cheley S, Bayley H, Gouaux JE (1996) Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore. Science 274(5294):1859–1866. https://doi.org/10.1126/science.274.5294.1859

    Article  CAS  PubMed  Google Scholar 

  27. Tsigkrimani M, Panagiotarea K, Paramithiotis S, Bosnea L, Pappa E, Drosinos EH, Skandamis PN, Mataragas M (2022) Microbial ecology of sheep milk, artisanal feta, and kefalograviera cheeses part II: technological, safety, and probiotic attributes of lactic acid bacteria isolates. Foods 11(3):459. https://doi.org/10.3390/foods11030459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Li T, Lyu L, Zhang Y, Dong K, Li Q, Guo X, Zhu Y (2021) A newly isolated E. thailandicus strain d5B with exclusively antimicrobial activity against C. difficile might be a novel therapy for controlling CDI. Genomics 113(1 Pt 2):475–483. https://doi.org/10.1016/j.ygeno.2020.09.032

    Article  CAS  PubMed  Google Scholar 

  29. Yin D, Guo Y, Li M, Wu W, Tang J, Liu Y, Chen F, Ni Y, Sun J, Zhang H, Zhao H, Hu F (2021) Performance of VITEK 2, E-test, Kirby-Bauer disk diffusion, and modified Kirby-Bauer disk diffusion compared to reference broth microdilution for testing tigecycline susceptibility of carbapenem-resistant K. pneumoniae and A. baumannii in a multicenter study in China. Eur J Clin Microbiol Infect Dis 40(6):1149–1154. https://doi.org/10.1007/s10096-020-04123-z

    Article  CAS  PubMed  Google Scholar 

  30. National Committee for Clinical Laboratory Standards, Wayne (2004) Performance standards for antimicrobial susceptibility testing. Informational supplement M100-S14

  31. Humphries R, Bobenchik AM, Hindler JA, Schuetz AN (2021) Overview of changes to the clinical and laboratory standards institute performance standards for antimicrobial susceptibility testing, M100. J Clin Microbiol 59(12):e0021321. https://doi.org/10.1128/JCM.00213-21

    Article  PubMed  Google Scholar 

  32. Al Kassaa I, Hamze M, Hober D, Chihib NE, Drider D (2014) Identification of vaginal Lactobacilli with potential probiotic properties isolated from women in North Lebanon. Microb Ecol 67(3):722–734. https://doi.org/10.1007/s00248-014-0384-7

    Article  PubMed  Google Scholar 

  33. Grauers Wiktorin H, Nilsson MS, Kiffin R, Sander FE, Lenox B, Rydström A, Hellstrand K, Martner A (2019) Histamine targets myeloid-derived suppressor cells and improves the anti-tumor efficacy of PD-1/PD-L1 checkpoint blockade. Cancer Immunol Immunother 68(2):163–174. https://doi.org/10.1007/s00262-018-2253-6

    Article  CAS  PubMed  Google Scholar 

  34. Lu Y, Li Y, Liu Q, Tian N, Du P, Zhu F, Han Y, Liu X, Liu X, Peng X, Wang X, Wu Y, Tong L, Li Y, Zhu Y, Wu L, Zhang P, Xu Y, Chen H, Li B, Tong X (2021) MondoA-thioredoxin-interacting protein axis maintains regulatory T-cell identity and function in colorectal cancer microenvironment. Gastroenterology 161(2):575-591.e16. https://doi.org/10.1053/j.gastro.2021.04.041

    Article  CAS  PubMed  Google Scholar 

  35. Ponnapakkam T, Saulsberry T, Hill T, Hill-Odom M, Goyal N, Anbalagan M, Liu J, Foroozesh M (2018) Inhibition of breast tumor growth in mice after treatment with ceramide analog 315. Anticancer Drugs 29(9):898–903. https://doi.org/10.1097/CAD.0000000000000675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Pereira V, Lopes C, Castro A, Silva J, Gibbs P, Teixeira P (2009) Characterization for enterotoxin production, virulence factors, and antibiotic susceptibility of Staphylococcus aureus isolates from various foods in Portugal. Food Microbiol 26(3):278–282. https://doi.org/10.1016/j.fm.2008.12.008

    Article  CAS  PubMed  Google Scholar 

  37. Guillemard E, Poirel M, Schäfer F, Quinquis L, Rossoni C, Keicher C, Wagner F, Szajewska H, Barbut F, Derrien M, Malfertheiner P (2021) A randomised, controlled trial: effect of a multi-strain fermented milk on the gut microbiota recovery after Helicobacter pylori therapy. Nutrients 13(9):3171. https://doi.org/10.3390/nu13093171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Zheng X, Nie W, Xu J, Zhang H, Liang X, Chen Z (2022) Characterization of antifungal cyclic dipeptides of Lacticaseibacillus paracasei ZX1231 and active packaging film prepared with its cell-free supernatant and bacterial nanocellulose. Food Res Int 162(Pt A):112024. https://doi.org/10.1016/j.foodres.2022.112024

    Article  CAS  PubMed  Google Scholar 

  39. Jia G, Liu X, Zhi A, Li J, Wu Y, Zhang Y (2021) Characterization and selection of Lactobacillus plantarum and Lactobacillus paracasei for prevention of oral bacterial infections from Chinese pickle. AMB Expr 11(1):84. https://doi.org/10.1186/s13568-021-01245-1

    Article  CAS  Google Scholar 

  40. Cannon JP, Lee TA, Bolanos JT, Danziger LH (2005) Pathogenic relevance of Lactobacillus: a retrospective review of over 200 cases. Eur J Clin Microbiol Infect Dis 24(1):31–40. https://doi.org/10.1007/s10096-004-1253-y

    Article  CAS  PubMed  Google Scholar 

  41. Huys G, Botteldoorn N, Delvigne F, De Vuyst L, Heyndrickx M, Pot B, Dubois JJ, Daube G (2013) Microbial characterization of probiotics-advisory report of the working group “8651 probiotics” of the belgian superior health council (SHC). Mol Nutr Food Res 57(8):1479–1504. https://doi.org/10.1002/mnfr.201300065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Flemming HC, Wingender J (2010) The biofilm matrix. Nat rev Microbiol 8(9):623–633. https://doi.org/10.1038/nrmicro2415

    Article  CAS  PubMed  Google Scholar 

  43. Hall-Stoodley L, Costerton JW, Stoodley P (2004) Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol 2(2):95–108. https://doi.org/10.1038/nrmicro821

    Article  CAS  PubMed  Google Scholar 

  44. Crabbé A, Jensen P, Bjarnsholt T, Coenye T (2019) Antimicrobial tolerance and metabolic adaptations in microbial biofilms. Trends Microbiol 27(10):850–863. https://doi.org/10.1016/j.tim.2019.05.003

    Article  CAS  PubMed  Google Scholar 

  45. Han C, Song J, Hu J, Fu H, Feng Y, Mu R, Xing Z, Wang Z, Wang L, Zhang J, Wang C, Dong L (2021) Smectite promotes probiotic biofilm formation in the gut for cancer immunotherapy. Cell Rep 34(6):108706. https://doi.org/10.1016/j.celrep.2021.108706

    Article  CAS  PubMed  Google Scholar 

  46. Lee KC, Liu CF, Lin TH, Pan TM (2010) Safety and risk assessment of the genetically modified Lactococci on rats intestinal bacterial flora. Int J Food Microbiol 142(1–2):164–169. https://doi.org/10.1016/j.ijfoodmicro.2010.06.018

    Article  CAS  PubMed  Google Scholar 

  47. Ren Z, Zhao A, Zhang J, Yang C, Zhong W, Mao S, Wang S, Yuan Q, Wang P, Zhang Y (2022) Safety and tolerance of Lacticaseibacillus paracasei N1115 in caesarean-born young children: a randomised, placebo-controlled trial. Benef Microbes 13(3):205–219. https://doi.org/10.3920/BM2021.0132

    Article  CAS  PubMed  Google Scholar 

  48. Mousavi Jam SA, Morshedi M, Yari Khosroushahi A, Eftekharsadat AT, Alipour M, Alipour B (2020) Preventive and tumor-suppressive effects of Lactobacillus paracasei X12 in rat model of colorectal cancer. Iran J Pharm Res 19(4):330–342. https://doi.org/10.22037/ijpr.2019.112135.13547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Orlando A, Refolo MG, Messa C, Amati L, Lavermicocca P, Guerra V, Russo F (2012) Antiproliferative and proapoptotic effects of viable or heat-killed Lactobacillus paracasei IMPC21 and Lactobacillus rhamnosus GG in HGC-27 gastric and DLD-1 colon cell lines. Nutr Cancer 64(7):1103–1111. https://doi.org/10.1080/01635581.2012

    Article  CAS  PubMed  Google Scholar 

  50. Choi SS, Kim Y, Han KS, You S, Oh S, Kim SH (2006) Effects of Lactobacillus strains on cancer cell proliferation and oxidative stress in vitro. Lett Appl Microbiol 42(5):452–458. https://doi.org/10.1111/j.1472-765X.2006.01913.x

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thanks to high-throughput screening platform for functional strains—Longseek: A versatile, automatic high-throughput zebrafish platform for drug and probiotic screening.

Funding

This study was funded by the National Natural Science Foundation of China (NNSFC) (No. 82003786); Guangdong Province Basic and Applied Basic Research Fund (No. 2019A1515110338).

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Authors and Affiliations

  1. Center of Human Microecology Engineering and Technology of Guangdong Province, Guangdong Longsee Biomedical Corporation, Guangzhou, 510535, Guangdong, China

    Tao Chen, Baoxia Li, Kangdi Zheng, Yan Liu & Zhao Zhang

  2. School of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, Guangdong, China

    Huimei Hu & Guoqiang Qian

  3. Department of Biochemistry, Basic Medical College, Jinan University, Guangzhou, 510630, Guangdong, China

    Jianwei Jiang

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  1. Tao Chen
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  2. Baoxia Li
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  4. Yan Liu
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  5. Zhao Zhang
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Contributions

TC, GQ and JJ conceptualized and designed the study. Material preparation, data collection and analysis were performed by BL, KZ, YL, ZZ and HH. The first draft of the manuscript was written by TC, and all authors critically revised all versions of the manuscript. Resources and supervision were provided by GQ and JJ. All authors read and approved the final manuscript.

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Correspondence to Yan Liu, Guoqiang Qian or Jianwei Jiang.

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The mice and were handled in strict accordance with the Experimental Animal Regulation Ordinances defined by the Laboratory Animal Welfare and Ethics Committee. The study was approved by the animal ethics committee of Daoke Pharmaceutical Technology (Guangdong) Co., Ltd under permit number (IACUC2022-0401).

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Chen, T., Li, B., Zheng, K. et al. Lactobacillus paracasei R3 Alleviates Tumor Progression in Mice with Colorectal Cancer. Curr Microbiol 81, 38 (2024). https://doi.org/10.1007/s00284-023-03525-4

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