Candidate probiotic Lactiplantibacillus plantarum HNU082 rapidly and convergently evolves within human, mice, and zebrafish gut but differentially influences the resident microbiome

Shi Huang, Shuaiming Jiang, Dongxue Huo, Celeste Allaband, Mehrbod Estaki, Victor Cantu, Pedro Belda-Ferre, Yoshiki Vázquez-Baeza, Qiyun Zhu, Chenchen Ma, Congfa Li, Amir Zarrinpar, Yang Yu Liu, Rob Knight, Jiachao Zhang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Improving probiotic engraftment in the human gut requires a thorough understanding of the in vivo adaptive strategies of probiotics in diverse contexts. However, for most probiotic strains, these in vivo genetic processes are still poorly characterized. Here, we investigated the effects of gut selection pressures from human, mice, and zebrafish on the genetic stability of a candidate probiotic Lactiplantibacillus plantarum HNU082 (Lp082) as well as its ecological and evolutionary impacts on the indigenous gut microbiota using shotgun metagenomic sequencing in combination with isolate resequencing methods. Results: We combined both metagenomics and isolate whole genome sequencing approaches to systematically study the gut-adaptive evolution of probiotic L. plantarum and the ecological and evolutionary changes of resident gut microbiomes in response to probiotic ingestion in multiple host species. Independent of host model, Lp082 colonized and adapted to the gut by acquiring highly consistent single-nucleotide mutations, which primarily modulated carbohydrate utilization and acid tolerance. We cultivated the probiotic mutants and validated that these gut-adapted mutations were genetically stable for at least 3 months and improved their fitness in vitro. In turn, resident gut microbial strains, especially competing strains with Lp082 (e.g., Bacteroides spp. and Bifidobacterium spp.), actively responded to Lp082 engraftment by accumulating 10–70 times more evolutionary changes than usual. Human gut microbiota exhibited a higher ecological and genetic stability than that of mice. Conclusions: Collectively, our results suggest a highly convergent adaptation strategy of Lp082 across three different host environments. In contrast, the evolutionary changes within the resident gut microbes in response to Lp082 were more divergent and host-specific; however, these changes were not associated with any adverse outcomes. This work lays a theoretical foundation for leveraging animal models for ex vivo engineering of probiotics to improve engraftment outcomes in humans. [MediaObject not available: see fulltext.]

Original languageEnglish (US)
Article number151
JournalMicrobiome
Volume9
Issue number1
DOIs
StatePublished - Dec 2021
Externally publishedYes

Keywords

  • Adaptive evolution
  • Lactiplantibacillus plantarum
  • Probiotic
  • Universal strategy

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

Fingerprint

Dive into the research topics of 'Candidate probiotic Lactiplantibacillus plantarum HNU082 rapidly and convergently evolves within human, mice, and zebrafish gut but differentially influences the resident microbiome'. Together they form a unique fingerprint.

Cite this