Candidate probiotic Lactiplantibacillus plantarum HNU082 rapidly and convergently evolves within human, mice, and zebrafish gut but differentially influences the resident microbiome
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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.
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In a previous study, probiotic strain Lp082 rapidly acquired adaptive mutations within the gut, significantly enhanced its carbon utilization and acid tolerance.
“In our previous study, we first demonstrated that a probiotic strain, Lactiplantibacillus plantarum HNU082 (Lp082), rapidly acquired adaptive mutations within the gut, significantly enhanced its carbon utilization and acid tolerance.25”
From Gut microbiota drives structural variation of exogenous probiotics to enhance colonization (2025) · cites this paper as [25]
The method for isolating and identifying Lp082 from feces has been established in previous research.
“The method for isolating and identifying Lp082 from feces has been established in previous research.25”
From Gut microbiota drives structural variation of exogenous probiotics to enhance colonization (2025) · cites this paper as [25]
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- Authors
- Huang, S., Jiang, S., Huo, D., Allaband, C., Estaki, M., Cantu, V., Belda-Ferre, P., Vázquez-Baeza, Y., Zhu, Q., Ma, C., Li, C., Zarrinpar, A., Liu, Y.-Y., Knight, R., & Zhang, J.
- Affiliations
- Hainan University (CN)
- University of California San Diego (US)
- UC San Diego Health System (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Knight, Rob
- Zhang, Jiachao
- ORCID
- Venue
- Microbiome
- Published
- 2021-06-30
- Volume
- 9
- Issue
- 1
- Pages
- 151-151
- ISSN
- 2049-2618 (ISSN-L)
- PMC
- PMC8247228
- OpenAlex
- W3177468406
- Cited by
- 61
- References
- 47
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 11 · 2023: 13 · 2022: 12 · 2021: 1
- FWCI
- 5.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Microbiome (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Natural Science Foundation of China (31701577)
- National Institutes of Health (T32 OD017863, K08 DK102902, R01AI141529, R01HD093761, R01AG067744)
- NIDDK (P30 DK120515, P30 DK063491, and UL1 TR001442)
- National Center for Complementary and Integrative Health (DP1-AT010885)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › Aquaculture disease management and microbiota
- Keywords
- Lactobacillus plantarum, point mutations, genetic stability, host-specific adaptation, human gut microbiome, mouse gut microbiome, Bacteroides, Bifidobacterium, carbohydrate utilization, acid resistance, probiotic engineering
- MeSH terms
- Gastrointestinal Microbiome, Animals, Bifidobacterium, Humans, Zebrafish, Probiotics, Mice, Microbiota
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