TY - JOUR
T1 - Candidate probiotic Lactiplantibacillus plantarum HNU082 rapidly and convergently evolves within human, mice, and zebrafish gut but differentially influences the resident microbiome
AU - Huang, Shi
AU - Jiang, Shuaiming
AU - Huo, Dongxue
AU - Allaband, Celeste
AU - Estaki, Mehrbod
AU - Cantu, Victor
AU - Belda-Ferre, Pedro
AU - Vázquez-Baeza, Yoshiki
AU - Zhu, Qiyun
AU - Ma, Chenchen
AU - Li, Congfa
AU - Zarrinpar, Amir
AU - Liu, Yang Yu
AU - Knight, Rob
AU - Zhang, Jiachao
N1 - Funding Information:
The project was supported by the National Natural Science Foundation of China (No. 31701577). CA is supported by NIH T32 OD017863. AZ is supported by NIH K08 DK102902, R21 MH117780, R01 HL148801. Y.-Y.L. is supported by NIH grants: R01AI141529, R01HD093761, R01AG067744, UH3OD023268, U19AI095219, and U01HL089856. This work was supported in part by NIDDK grant P30 DK120515, P30 DK063491, and UL1 TR001442 and NCCIH grant DP1-AT010885. This work was also supported by IBM Research through the AI Horizons Network, UC San Diego AI for Healthy Living program in partnership with the UC San Diego Center for Microbiome Innovation.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.]
AB - 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.]
KW - Adaptive evolution
KW - Lactiplantibacillus plantarum
KW - Probiotic
KW - Universal strategy
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U2 - 10.1186/s40168-021-01102-0
DO - 10.1186/s40168-021-01102-0
M3 - Article
C2 - 34193290
AN - SCOPUS:85110076121
VL - 9
JO - Microbiome
JF - Microbiome
SN - 2049-2618
IS - 1
M1 - 151
ER -