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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

Abstract

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.


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  • Table 1   Research course of probiotic LCZ

    时间

    LCZ

    实验类型和肠道分析

    文献

    第一阶段: 单菌株组学体外评价阶段

    2002年

    分离和筛选

    体外实验

    [11]

    2008年

    全基因组测定

    体外实验

    [15]

    2009年

    LCZ与多株益生菌体外益生活性比较

    体外实验

    [13]

    2009~2011年

    LCZ 生长、耐酸耐胆盐比较蛋白组学

    体外实验

    [16~18]

    2009年

    LCZ发酵马乳特性和胃肠道转运耐受性

    体外实验

    [36]

    2009年

    LCZ发酵豆乳和牛乳特性以及体外胃肠道转运耐受性

    体外实验

    [37]

    2010年

    LCZ发酵契达干酪的ACE抑制活性和γ氨基丁酸产生

    体外实验

    [38]

    2013年

    LCZ调节巨噬细胞活性

    体外细胞实验

    [24]

    第二阶段: 肠道优势菌结合益生功能体内评价阶段

    2006年

    LCZ调节正常小鼠免疫功能IgG和肠黏膜SIgA

    动物实验

    [39]

    2008年

    LCZ调节免疫功能

    动物实验

    [23]

    2010年

    LCZ抵抗脂质过氧化

    动物实验

    [26]

    2010年

    LCZ对肝癌荷瘤小鼠的抑癌作用

    动物实验

    [25]

    2012年

    LCZ降低血脂水平试验

    动物实验肝脏芯片

    [28]

    2014年

    LCZ改善糖耐量受损

    动物实验肠道优势菌Q-PCR

    [30]

    2014年

    LCZ抵抗二型糖尿病

    动物实验肠道优势菌Q-PCR

    [31]

    第三阶段: 益生功能评价与肠道菌群组学结合的阶段

    2014年

    LCZ调节不同年龄段人体肠道菌群

    小人群试验; 肠道菌群454焦磷酸测序

    [32,33]

    2015年

    LCZ抵抗乳房炎

    动物实验肠道宏基因组学测序

    待发表

    2017年

    LCZ减少脂肪累积

    动物实验肠道宏基因组学测序

    待发表

    2017年

    LCZ抵抗动物结肠癌效应

    动物实验肠道16SrDNA三代测序

    [34]

    2017年

    LCZ调节肠道慢性炎症

    动物实验肠道16SrDNA三代测序

    待发表

    2018年

    LCZ预防呼吸道感染和改善老年人群红细胞

    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

    2018年

    LCZ改变人体肠道微生物转录

    小人群样本; 肠道宏基因组学和宏转录组学测序

    待发表

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