Probiotic-directed modulation of gut microbiota is basal microbiome dependent

Abstract

As an effective means to improve quality of life and prevent diseases, the demand for probiotics and related products has increased in recent years. However, it is still unclear whether a particular probiotic strain will have similar beneficial effects on healthy adults from different regions. In this study, the probiotic Lactobacillus casei Zhang (LCZ) was consumed by healthy adults from six different Asian regions and the changes in gut microbiota were compared using PacBio single molecule, real-time (SMRT) sequencing technology based on samples collected before, during and after consumption of LCZ. Our results reveal that the effect of LCZ consumption on individuals was closely related to the composition of that individual's basal gut microbiota. A Gut Microbiota Variability Index (GMVI) was proposed to quantitatively compare the effects of LCZ on human gut microecology. Subjects from Xinjiang and Singapore regions had the highest and lowest GMVI, respectively. In general, consumption of LCZ increased the relative abundance of certain beneficial bacteria such as Lactobacillus, Roseburia, Coprococcus and Eubacterium rectale, while it inhibited growth of certain harmful bacteria such as Blautia and Ralstonia pickettii. In addition, consumption of LCZ was responsible for the conversion of some participants from Prevotella copri/Faecalibacterium prausnitzii (PF) enterotype to Faecalibacterium prausnitzii/Bacteroides dorei (FB) enterotype and consistently increased the abundance of lactic acid bacteria in the gut. It also increased/enhanced phosphate metabolic modules, amino acid transport systems, and isoleucine biosynthesis, but conversely decreased lipopolysaccharide biosynthesis. These changes could have health benefits for healthy adults.

Keywords: lactobacillus casei Zhang; Probiotics; enteropypes; gut microbiota; lactic acid bacteria.

Figure 1.

Basal composition characteristics of the gut microbiota of participants from six regions prior to consumption of the probiotic LCZ. a, b and c represent: phylum-level, genus-level and species-level bacterial composition, respectively, as determined using PacBio SMRT sequencing of 16 S rRNA genes. Each pie chart and column chart shows the mean composition of participants from each region. d: the relationship between F/B index and BMI index of participants from each region. e shows the core OTUs of gut microbiota in participants from each region. The color of squares represents the median of the relative abundance of each OTU.

Figure 2.

Comparison of α diversity indicators and species-level bacterial composition of the gut microbiota amongst participants from six regions prior to consumption of the probiotic LCZ. a and b represent: the number of observed OTUs and Shannon diversity index of the gut microbiota from participants from each region, respectively. Dots represent outliers from the respective groups. c: the gut microbiota that vary significantly in abundance amongst subjects from different regions. Species corresponding to the diagonal indicates that the average relative abundance of those species in this region are higher than those in the other five regions.

Figure 3.

Enterotype analysis based on species-level bacterial composition of the gut microbiota of participants from six regions prior to consumption of the probiotic LCZ. a: all subjects divided into two different enterotypes. b: clustering of all the participants based on species composition data. The optimal number of clusters was chosen by maximizing the Calinski–Harabasz index and the clustering is displayed in the PCA plot. c, d and e represent: the relative abundances of P. copri, F. prausnitzii and B. dorei in each enterotype, respectively. f, g and h represent: the relationship between the relative abundances of P. copri, F. prausnitzii, B. dorei and the whole composition of gut microbiota, respectively.

Figure 4.

Effects of LCZ intake on the whole gut microbiota composition of participants from six regions. a and b represent: PCoA score plots based on unweighted and weighted UniFrac distance, respectively. Each point represents the mean principal component scores of all participants from one region at one time point, and the error bar represents the standard deviation. c: the height of each column represents the average distance amongst all samples at the same time point in a particular region. The error bar indicates the standard deviation of the distance between samples. d: the Weighed UniFrac distances of gut microbiota in participants before and after LCZ intake by paired calculation. There is no significant difference between groups with the same letter.

Figure 5.

Composition characteristics of gut LAB in participants from six regions. a and b represent: genus-level and species-level gut LAB composition in participants from six regions, respectively. c and e represent: the number of observed OTUs and Shannon diversity index of gut LAB in participants from six regions, respectively. Dots represent outliers of the respective groups. d: LefSe analysis of gut LAB in participants from six regions at day 0. f: LAB species that with significantly relative abundance between PF and FB enterotypes.

Figure 6.

Effect of consumption of the probiotic LCZ on the gut LAB of participants from six regions. a: Changes in the number of observed OTUs of gut LAB in participants from each region at different times during the period of consumption of LCZ. b: The quantity of Lactobacillus casei as determined using ddPCR.