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Tunable control of B. infantis abundance and gut metabolites by co-administration of human milk oligosaccharides.
Reens, Abigail L; Cosetta, Casey M; Saur, Russell; Trofimuk, Olivia; Brooker, Sarah L; Lee, Martin L; Sun, Adam K; McKenzie, Gregory J; Button, Julie E.
Afiliação
  • Reens AL; Prolacta Bioscience, Duarte, CA, USA.
  • Cosetta CM; Prolacta Bioscience, Duarte, CA, USA.
  • Saur R; Prolacta Bioscience, Duarte, CA, USA.
  • Trofimuk O; Prolacta Bioscience, Duarte, CA, USA.
  • Brooker SL; Prolacta Bioscience, Duarte, CA, USA.
  • Lee ML; Prolacta Bioscience, Duarte, CA, USA.
  • Sun AK; Department of Biostatistics, University of California Los Angeles Fielding School of Public Health, Los Angeles CA, USA.
  • McKenzie GJ; Prolacta Bioscience, Duarte, CA, USA.
  • Button JE; Prolacta Bioscience, Duarte, CA, USA.
Gut Microbes ; 16(1): 2304160, 2024.
Article em En | MEDLINE | ID: mdl-38235736
ABSTRACT
Precision engineering of the gut microbiome holds promise as an effective therapeutic approach for diseases associated with a disruption in this microbial community. Engrafting a live biotherapeutic product (LBP) in a predictable, controllable manner is key to the consistent success of this approach and has remained a challenge for most LBPs under development. We recently demonstrated high-level engraftment of Bifidobacterium longum subsp. infantis (B. infantis) in adults when co-dosed with a specific prebiotic, human milk oligosaccharides (HMO). Here, we present a cellular kinetic-pharmacodynamic approach, analogous to pharmacokinetic-pharmacodynamic-based analyses of small molecule- and biologic-based drugs, to establish how HMO controls expansion, abundance, and metabolic output of B. infantis in a human microbiota-based model in gnotobiotic mice. Our data demonstrate that the HMO dose controls steady-state abundance of B. infantis in the microbiome, and that B. infantis together with HMO impacts gut metabolite levels in a targeted, HMO-dependent manner. We also found that HMO creates a privileged niche for B. infantis expansion across a 5-log range of bacterial inocula. These results demonstrate remarkable control of both B. infantis levels and the microbiome community metabolic outputs using this synbiotic approach, and pave the way for precision engineering of desirable microbes and metabolites to treat a range of diseases.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Bifidobacterium / Microbioma Gastrointestinal Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Gut Microbes Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Bifidobacterium / Microbioma Gastrointestinal Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Gut Microbes Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos