ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Food Microbiology
Genomic and Phenotypic Characterization of Two Novel Human-Derived Limosilactobacillus reuteri Strains with Unique Probiotic Traits
Provisionally accepted- Sun Yat-sen University, Guangzhou, China
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Abstract Background: Limosilactobacillus reuteri is recognized for its diverse host-beneficial functions, though these are highly strain-specific. This study aimed to genomically and functionally characterize two novel L. reuteri isolates to assess their potential for specific health-associated applications. Methods: We isolated and genomically sequenced two novel L. reuteri strains, LLR2 and LLR3. Their functional potential was systematically evaluated through in vitro assays, including assessment of reuterin production, the ability to stimulate mucin production in co-culture with intestinal epithelial LS174T cells, and anti-inflammatory activity in a human brain microvascular endothelial cell (hCMEC/D3) model of LPS-induced inflammation. Results: Comparative genomic analysis revealed distinct genetic architectures between LLR2 and LLR3, reflecting divergent evolutionary trajectories. Functionally, pronounced strain-specific differences were observed: LLR3 produced the antimicrobial compound reuterin, while LLR2 did not. In co-culture with LS174T cells, both strains decrease the production of Mucin-2, a key component of the gut barrier, with LLR2 showing significantly greater efficacy. Conversely, in the hCMEC/D3 inflammation model, LLR3 demonstrated a significantly stronger anti-inflammatory effect, suppressing the LPS-induced expression of IL-6 and TNF-α. Conclusions: This study expands the genomic repository of L. reuteri and provides clear experimental evidence of strain-specific functional profiles. Our findings establish a foundation for the precision selection of L. reuteri strains such as LLR2 for gut barrier reinforcement and LLR3 for inflammation modulation in tailored applications for gut health and gut-brain axis research.
Keywords: Comparative genomics, Limosilactobacillus reuteri, Probiotics, Strain isolation, Strain-specificity
Received: 11 Oct 2025; Accepted: 28 Nov 2025.
Copyright: © 2025 Yang, Zhan, Wu, Wang, Zou, Li, Lu and Ge. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhenhuang Ge
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
