Phage endolysin enables targeted manipulation of the small intestinal microbiota and uncovers niche overlap between oral and butyrate-producing taxa
- 1Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland
- 2Present Address: Interactions Hôtes-Pathogènes-Environnements (IHPE), UMR 5244, CNRS, Université de Montpellier, Université de Perpignan, IFREMER, Montpellier, France
- 3Laboratory of Bacteriophages and Phage Therapy, Center for Research and Innovation in Clinical Pharmaceutical Sciences (CRISP), Lausanne University Hospital, Lausanne, Switzerland
Abstract
Small intestinal oral bacterial overgrowth (SIOBO) is associated with impaired nutrient absorption and is a key contributor to environmental enteric disorder (EED) and stunted child growth. Here, we explore the use of a phage-derived lysin as a precision antimicrobial to selectively target Streptococcus salivarius within complex microbial communities. Using a newly developed bioinformatic and wet-lab pipeline, we identified, cloned, and produced a prophage-encoded lysin from S. salivarius and demonstrated its potent and specific lytic activity against 49 S. salivarius strains isolated from stunted children, while sparing related species such as S. mitis, S. parasanguinis, and S. thermophilus. Application of the lysin to human stool-derived in vitro communities and to mice colonized with S. salivarius led to an approximate 2–3 log reduction in S. salivarius abundance while preserving overall bacterial community. We observed a negative correlation between S. salivarius and Coprococcus (now Allocoprococcus) comes in vitro, and Eubacterium xylanophilum, Akkermansia, Lactobacillus and Ruminococcus in vivo. Spent-medium assays confirmed niche overlap between 10 clinical strains of S. salivarius and 28 taxa commonly recognized as butyrate producers. These results suggest that phage-derived lysins offer multiple benefits by selectively removing ectopically colonized oral taxa and indirectly promoting beneficial anaerobes.
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BibTeX
@article{garneau2026phage,
title = {{Phage endolysin enables targeted manipulation of the small intestinal microbiota and uncovers niche overlap between oral and butyrate-producing taxa}},
author = {Julian R. Garneau and Aline Altenried and Youzheng Teo and Xiaobing Wu and Sarah C. McHugh and Michael Taschner and Carla Hernández-Cabanyero and Johann Mignolet and Pénélope Gomes and Hugues de Villiers de la Noue and Grégory Resch and Pascale Vonaesch},
journal = {NPJ Biofilms and Microbiomes},
year = {2026},
month = jul,
doi = {10.1038/s41522-026-01087-4},
url = {https://doi.org/10.1038/s41522-026-01087-4},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Phage endolysin enables targeted manipulation of the small intestinal microbiota and uncovers niche overlap between oral and butyrate-producing taxa
AU - Julian R. Garneau
AU - Aline Altenried
AU - Youzheng Teo
AU - Xiaobing Wu
AU - Sarah C. McHugh
AU - Michael Taschner
AU - Carla Hernández-Cabanyero
AU - Johann Mignolet
AU - Pénélope Gomes
AU - Hugues de Villiers de la Noue
AU - Grégory Resch
AU - Pascale Vonaesch
PY - 2026
DA - 2026/07/13
JO - NPJ Biofilms and Microbiomes
DO - 10.1038/s41522-026-01087-4
UR - https://doi.org/10.1038/s41522-026-01087-4
AB - Small intestinal oral bacterial overgrowth (SIOBO) is associated with impaired nutrient absorption and is a key contributor to environmental enteric disorder (EED) and stunted child growth. Here, we explore the use of a phage-derived lysin as a precision antimicrobial to selectively target Streptococcus salivarius within complex microbial communities. Using a newly developed bioinformatic and wet-lab pipeline, we identified, cloned, and produced a prophage-encoded lysin from S. salivarius and demonstrated its potent and specific lytic activity against 49 S. salivarius strains isolated from stunted children, while sparing related species such as S. mitis, S. parasanguinis, and S. thermophilus. Application of the lysin to human stool-derived in vitro communities and to mice colonized with S. salivarius led to an approximate 2–3 log reduction in S. salivarius abundance while preserving overall bacterial community. We observed a negative correlation between S. salivarius and Coprococcus (now Allocoprococcus) comes in vitro, and Eubacterium xylanophilum, Akkermansia, Lactobacillus and Ruminococcus in vivo. Spent-medium assays confirmed niche overlap between 10 clinical strains of S. salivarius and 28 taxa commonly recognized as butyrate producers. These results suggest that phage-derived lysins offer multiple benefits by selectively removing ectopically colonized oral taxa and indirectly promoting beneficial anaerobes.
SN - 2055-5008
ER -