Little is known about the replication and dynamic transcription of probiotics during their “passenger” journey in the human GI tract, which has therefore limited the understanding of their probiotic mechanisms. Here, metagenomic and metatranscriptomic sequencing was used to expose the in vivo expression patterns of the probiotic Lactobacillus casei Zhang (LcZ), which was compared with its in vitro growth transcriptomes, as well as the dynamics of the indigenous microbiome response to probiotic consumption. Extraction of the strain-specific reads revealed that replication and transcripts from the ingested LcZ were increased, while those from the resident L. casei strains remained unchanged. Mapping of all sequencing reads to LcZ genome showed that gene expression in vitro and in vivo differed dramatically. Approximately 39% of mRNAs and 45% of sRNAs of LcZ well-expressed were repressed after ingestion into human gut. The expression of ABC transporter genes and amino acid metabolism genes was induced at day 14 of ingestion, and genes for sugar and SCFA metabolism were activated at day 28 of ingestion. Expression of rli28c sRNA with peaked expression during the in vitro stationary phase was also activated in the human gut; this sRNA repressed LcZ growth and lactic acid production in vitro. However, the response of the human gut microbiome to LcZ was limited and heterogeneous. These findings implicate the ingested probiotic has to change its transcription patterns to survive and adapt in the human gut, and the time-dependent activation patterns indicate highly dynamic cross-talk between the probiotic and human gut microbes.

人们对益生菌在人类胃肠道中的“过客”旅程中的复制和动态转录知之甚少，因此限制了对其益生菌机制的理解。在这里，宏基因组和宏转录组测序用于揭示益生菌干酪乳杆菌(LcZ) 的体内表达模式，并将其与其体外生长转录组进行比较，以及本地微生物组对益生菌消耗的反应动态。菌株特异性读数的提取显示，来自摄入的 LcZ 的复制和转录增加了，而来自常驻干酪乳杆菌的复制和转录增加了应变保持不变。将所有测序读数映射到 LcZ 基因组表明体外和体内的基因表达存在显着差异。在摄入人体肠道后，大约 39% 的 LcZ mRNA 和 45% 的 sRNAs 被抑制。ABC 转运蛋白基因和氨基酸代谢基因在摄入第 14 天被诱导表达，糖和 SCFA 代谢基因在摄入第 28 天被激活。在体外稳定期达到峰值的 rli28c sRNA 在人肠道中的表达也被激活；这种 sRNA 在体外抑制了 LcZ 的生长和乳酸的产生。然而，人类肠道微生物群对 LcZ 的反应是有限且异质的。这些发现表明，摄入的益生菌必须改变其转录模式才能在人类肠道中生存和适应，