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

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.