Chinese Science Bulletin, Volume 64 , Issue 3 : 307-314(2019) https://doi.org/10.1360/N972018-00591

Probiotic effects of Lactobacillus casei Zhang: From single strain omics to metagenomics

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  • ReceivedAug 28, 2018
  • AcceptedOct 23, 2018
  • PublishedNov 26, 2018


Lactobacillus casei Zhang (LCZ) is a well-studied probiotic bacterium that was inspired by traditional Mongolian medicine and isolated from naturally fermented koumiss in Inner Mongolia. There are three major stages of LCZ research and development. It contains single strain omics and in vitro evaluation stage (Stage 1), gut dominated microbes and in vivo evaluation stage (Stage 2) as well as metagenomics and clinical evaluation stage (Stage 3). LCZ was screened out from acid resistance, bile salt tolerance and processed favorable effects of in vitro cell adhesion characteristics and regulation of macrophage activity. And then, the whole genome of LCZ was determined and analyzed, which is the first identified Lactobacillus genome in China at 2008. Antibiotics resistance experiments showed a strong stability of LCZ genome under amoxicillin or gentamycin exposure through 2000 generations of laboratory evolution. A set of functional proteins such as NagA and NagB were identified from LCZ proteomics of growth process, acid stress or bile salt tolerance. Furthermore in vivo tests, LCZ has been demonstrated to process several beneficial effects including regulating microbiota abundance and ratios, lipid peroxidation inhibition and increasing antioxidant enzymes activities, regulating cellular and humoral immunity and tumor associated immune function, hepatoprotective effect and inhibition of liver transplanted tumor growth. Researchers have long appreciated the benefits of the gut microbiota to health. Moreover, LCZ was confirmed to promote the intestinal Bacteroides abundance and thereby alleviating impaired glucose tolerance and preventing type 2 diabetes mellitus by Q-PCR methods. Using the third generation PacBio sequencing technology, LCZ could delay the colon cancer progression in mice via altered gut microbiota composition and microbial acetic acid production. Detailedly, Alloprevotella rava and Parabacteroides merdae are the precise potential health-promoting species increased by LCZ intake. In addition to modulate gut microbiota composition, probiotic LCZ also manipulate bile acids, affects its conversation and induced tissue influx of chloride ion, which can impact the expression of chloride ion related proteins (eg.CLCN3 and CFTR). Small-scale human trial indicated that LCZ could maintain the abundance of gut microbiota, increase the number of beneficial bacteria and reduce potential harmful bacteria via 454 pyrosequencing. In 2018, a large-scale, randomized, double-blind and placebo-controlled study was conducted by LCZ administration in Malaysian population. In adult subjects, it confirmed that LCZ could prevent upper respiratory tract infection including reducing the number of days for pharyngeal and general flu symptoms as well as nasal symptoms. In elderly populations, LCZ not only reduced nasal symptoms but also alleviated aged index including improving the mean corpuscular hemoglobin concentration and erythrocyte sedimentation rate. These are attributing to microbiota modulation and its mediated immunity such as increased anti-inflammatory IL-4. It is suggested that LCZ will exert more benefits in microbiota regulation and became a promising health food / special medical food for preventive or therapeutic effects.


[1] Cani P D, Delzenne N M. The gut microbiome as therapeutic target. Pharmacol Therapeutics, 2011, 130: 202-212 CrossRef Google Scholar

[2] Panwar H, Calderwood D, Grant I R, et al. Lactobacillus strains isolated from infant faeces possess potent inhibitory activity against intestinal alpha- and beta-glucosidases suggesting anti-diabetic potential. Eur J Nutr, 2014, 53: 1465-1474 CrossRef Google Scholar

[3] Larsen B, Monif G R G. Understanding the bacterial flora of the female genital tract. Clinical Infect Dis, 2001, 32: e69-e77 CrossRef Google Scholar

[4] Karimi G, Sabran M R, Jamaluddin R, et al. The anti-obesity effects of Lactobacillus casei strain Shirota versus Orlistat on high fat diet-induced obese rats. Food Nutrition Res, 2015, 59: 29273 CrossRef Google Scholar

[5] Ashraf R, Shah N P. Immune system stimulation by probiotic microorganisms. Critical Rev Food Sci Nutrition, 2014, 54: 938-956 CrossRef Google Scholar

[6] Dos Reis S A, da Conceição L L, Siqueira N P, et al. Review of the mechanisms of probiotic actions in the prevention of colorectal cancer. Nutrition Res, 2017, 37: 1-19 CrossRef Google Scholar

[7] Dong J, Zhang Y, Zhang H. Chapter 2: Health properties of traditional fermented Mongolian milk foods. In: Liong M T, ed. Beneficial Microorganisms in Food & Nutraceutical. Netherlands: Springer, 2015. Google Scholar

[8] Kozhakhmetov S, Tynybayeva I, Baikhanova D, et al. Metagenomic analysis of koumiss in Kazakhstan. Cent Asian J Glob Health, 2014, 3(Suppl): 163. Google Scholar

[9] Yao G, Yu J, Hou Q, et al. A perspective study of koumiss microbiome by metagenomics analysis based on single-cell amplification technique. Front Microbiol, 2017, 8: 165. Google Scholar

[10] Chen Y, Wang Z, Chen X, et al. Identification of angiotensin I-converting enzyme inhibitory peptides from koumiss, a traditional fermented mare's milk. J Dairy Sci, 2010, 93: 884-892 CrossRef Google Scholar

[11] Wu R, Wang L, Wang J, et al. Isolation and preliminary probiotic selection of lactobacilli from koumiss in Inner Mongolia. J Basic Microbiol, 2009, 49: 318-326 CrossRef Google Scholar

[12] Del Piano M, Morelli L, Strozzi G P, et al. Probiotics: From research to consumer. Digestive Liver Dis, 2006, 38: S248-S255 CrossRef Google Scholar

[13] Guo Z, Wang J, Yan L, et al. In vitro comparison of probiotic properties of Lactobacillus casei Zhang, a potential new probiotic, with selected probiotic strains. LWT - Food Sci Tech, 2009, 42: 1640-1646 CrossRef Google Scholar

[14] Hamon E, Horvatovich P, Bisch M, et al. Investigation of Biomarkers of Bile Tolerance in Lactobacillus casei Using Comparative Proteomics. J Proteome Res, 2012, 11: 109-118 CrossRef Google Scholar

[15] Zhang W, Yu D, Sun Z, et al. Complete genome sequence of Lactobacillus casei Zhang, a new probiotic strain isolated from traditional homemade koumiss in Inner Mongolia, China. J Bacteriology, 2010, 192: 5268-5269 CrossRef Google Scholar

[16] Wu R, Wang W, Yu D, et al. Proteomics Analysis of Lactobacillus casei Zhang, a New Probiotic Bacterium Isolated from Traditional Home-made Koumiss in Inner Mongolia of China. Mol Cell Proteomics, 2009, 8: 2321-2338 CrossRef Google Scholar

[17] Wu R, Zhang W, Sun T, et al. Proteomic analysis of responses of a new probiotic bacterium Lactobacillus casei Zhang to low acid stress. Int J Food MicroBiol, 2011, 147: 181-187 CrossRef Google Scholar

[18] Wu R, Sun Z, Wu J, et al. Effect of bile salts stress on protein synthesis of Lactobacillus casei Zhang revealed by 2-dimensional gel electrophoresis. J Dairy Sci, 2010, 93: 3858-3868 CrossRef Google Scholar

[19] Koskenniemi K, Laakso K, Koponen J, et al. Proteomics and Transcriptomics Characterization of Bile Stress Response in Probiotic Lactobacillus rhamnosus GG. Mol Cell Proteomics, 2011, 10: M110.002741 CrossRef Google Scholar

[20] Alcántara C, Zúñiga M. Proteomic and transcriptomic analysis of the response to bile stress of Lactobacillus casei BL23. Microbiology, 2012, 158: 1206–1218. Google Scholar

[21] Guo H, Pan L, Li L, et al. Characterization of Antibiotic Resistance Genes from Lactobacillus Isolated from Traditional Dairy Products. J Food Sci, 2017, 82: 724-730 CrossRef Google Scholar

[22] Zhang W, Guo H, Cao C, et al. Adaptation of Lactobacillus casei Zhang to gentamycin involves an alkaline shock protein. Front Microbiol, 2017, 8: 2316 CrossRef Google Scholar

[23] Ya T, Zhang Q, Chu F, et al. Immunological evaluation of Lactobacillus casei Zhang: A newly isolated strain from koumiss in Inner Mongolia, China. BMC Immunol, 2008, 9: 68 CrossRef Google Scholar

[24] Wang Y, Xie J, Wang N, et al. Lactobacillus casei Zhang modulate cytokine and Toll-like receptor expression and beneficially regulate poly I:C-induced immune responses in RAW264.7 macrophages. Microbiol Immunol, 2013, 57: 54-62 CrossRef Google Scholar

[25] Tuo Y, Du R T, Zhang H P. Antitumor effect and mechanism of probiotic Lb.casei Zhang on H22 tumor cell bearing mice (in Chinese). Cancer Res Prev Treatment, 2010, 37: 463–465 [托娅, 杜瑞亭, 张和平. 益生菌Lb.casei Zhang对H22荷瘤小鼠的抗肿瘤作用及机制. 肿瘤防治研究, 2010, 37: 463–465]. Google Scholar

[26] Zhang Y, Du R, Wang L, et al. The antioxidative effects of probiotic Lactobacillus casei Zhang on the hyperlipidemic rats. Eur Food Res Technol, 2010, 231: 151-158 CrossRef Google Scholar

[27] Zhang Y, Du R T, He Q W, et al. Effect of Lactobacillus casei Zhang administration on liver lipids metabolism of high-fat diet induced hypercholesterolemia rats (in Chinese). Sci Agric Sin, 2012, 45: 943–950 [张勇, 杜瑞亭, 何秋雯, 等. 饲喂益生菌Lactobacillus casei Zhang对高脂日量大鼠肝脏脂质代谢的作用. 中国农业科学, 2012, 45: 943–950]. Google Scholar

[28] Zhong Z, Zhang W, Du R, et al. Lactobacillus casei Zhang stimulates lipid metabolism in hypercholesterolemic rats by affecting gene expression in the liver. Eur J Lipid Sci Technol, 2012, 114: 244-252 CrossRef Google Scholar

[29] Wang Y, Li Y, Xie J, et al. Protective effects of probiotic Lactobacillus casei Zhang against endotoxin- and d-galactosamine-induced liver injury in rats via anti-oxidative and anti-inflammatory capacities. Int ImmunoPharmacol, 2013, 15: 30-37 CrossRef Google Scholar

[30] Zhang Y, Wang L, Zhang J, et al. Probiotic Lactobacillus casei Zhang ameliorates high-fructose-induced impaired glucose tolerance in hyperinsulinemia rats. Eur J Nutr, 2014, 53: 221-232 CrossRef Google Scholar

[31] Zhang Y, Guo X, Guo J, et al. Lactobacillus casei reduces susceptibility to type 2 diabetes via microbiota-mediated body chloride ion influx. Sci Rep, 2014, 4: 5654 CrossRef ADS Google Scholar

[32] Kwok L Y, Wang L, Zhang J, et al. A pilot study on the effect of Lactobacillus casei Zhang on intestinal microbiota parameters in Chinese subjects of different age. Beneficial Microbes, 2014, 5: 295-304 CrossRef Google Scholar

[33] Zhang J, Wang L, Guo Z, et al. 454 pyrosequencing reveals changes in the faecal microbiota of adults consuming Lactobacillus casei Zhang. FEMS Microbiol Ecol, 2014, 88: 612-622 CrossRef Google Scholar

[34] Zhang Y, Ma C, Zhao J, et al. Lactobacillus casei Zhang and vitamin K2 prevent intestinal tumorigenesis in mice via adiponectin-elevated different signaling pathways. Oncotarget, 2017, 8: 24719–24727. Google Scholar

[35] Hor Y Y, Lew L C, Lau A S Y, et al. Probiotic Lactobacillus casei Zhang (LCZ) alleviates respiratory, gastrointestinal & RBC abnormality via immuno-modulatory, anti-inflammatory & anti-oxidative actions. J Funct Foods, 2018, 44: 235-245 CrossRef Google Scholar

[36] Zhou Q, Wang J, Guo Z, et al. Fermentation characteristics and transit tolerance of Lactobacillus casei Zhang in reconstituted mare milk during storage. Int J Dairy Tech, 2009, 62: 249-254 CrossRef Google Scholar

[37] Wang J, Guo Z, Zhang Q, et al. Fermentation characteristics and transit tolerance of probiotic Lactobacillus casei Zhang in soymilk and bovine milk during storage. J Dairy Sci, 2009, 92: 2468-2476 CrossRef Google Scholar

[38] Wang H K, Dong C, Chen Y F, et al. A new probiotic cheddar cheese with high ACE-inhibitory activity and γ-aminobutyric acid content produced with koumiss-derived Lactobacillus casei Zhang. Food Tech Biotechnol, 2010, 48: 1–3. Google Scholar

[39] Zhang H P, Zhang Q J, Menghe B, et al. Effect of oral administration of L. casei Zhang on T-lymphocyte subclass, serum IgG and intestinal mucous SIgA of mouse (in Chinese). Chin Dairy Ind, 2006, 34: 4–8 [张和平, 张七斤, 孟和毕力格, 等. L.casei Zhang对小鼠T淋巴细胞亚群及血清IgG和肠黏膜SIgA的影响. 中国乳品工业, 2006, 34: 4–8]. Google Scholar

[40] Sivananthan K, Petersen A M. Review of Saccharomyces boulardii as a treatment option in IBD. ImmunoPharmacol ImmunoToxicol, 2018, 11: 1-11 CrossRef Google Scholar

  • Table 1   Research course of probiotic LCZ





    第一阶段: 单菌株组学体外评价阶段














    LCZ 生长、耐酸耐胆盐比较蛋白组学



















    第二阶段: 肠道优势菌结合益生功能体内评价阶段





























    第三阶段: 益生功能评价与肠道菌群组学结合的阶段



    小人群试验; 肠道菌群454焦磷酸测序




















    马来西亚人群; 165人随机双盲安慰剂对照试验; 肠道宏基因组学测序

    [35], 测序数据待发表



    小人群样本; 肠道宏基因组学和宏转录组学测序


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