Commensal consortia decolonize Enterobacteriaceae via ecological control

Munehiro Furuichi, Takaaki Kawaguchi, Marie-Madlen Pust, Keiko Yasuma-Mitobe, Damian R. Plichta, Naomi Hasegawa, Takashi Ohya, Shakti K. Bhattarai, Satoshi Sasajima, Yoshimasa Aoto, Timur Tuganbaev, Mizuki Yaginuma, Masahiro Ueda, Nobuyuki Okahashi, Kimiko Amafuji, Yuko Kiridoshi, Kayoko Sugita, Martin Stražar, Julian Avila-Pacheco, Kerry Pierce, Clary B. Clish, Ashwin N. Skelly, Masahira Hattori, Nobuhiro Nakamoto, Silvia Caballero, Jason M. Norman, Bernat Olle, Takeshi Tanoue, Wataru Suda, Makoto Arita, Vanni Bucci, Koji Atarashi, Ramnik J. Xavier () and Kenya Honda ()
Additional contact information
Munehiro Furuichi: Keio University School of Medicine
Takaaki Kawaguchi: Keio University School of Medicine
Marie-Madlen Pust: Broad Institute of MIT and Harvard
Keiko Yasuma-Mitobe: Keio University School of Medicine
Damian R. Plichta: Broad Institute of MIT and Harvard
Naomi Hasegawa: Keio University School of Medicine
Takashi Ohya: Keio University School of Medicine
Shakti K. Bhattarai: UMass Chan Medical School
Satoshi Sasajima: Keio University School of Medicine
Yoshimasa Aoto: Keio University School of Medicine
Timur Tuganbaev: Keio University School of Medicine
Mizuki Yaginuma: Keio University School of Medicine
Masahiro Ueda: RIKEN Center for Integrative Medical Sciences
Nobuyuki Okahashi: RIKEN Center for Integrative Medical Sciences
Kimiko Amafuji: Keio University School of Medicine
Yuko Kiridoshi: Keio University School of Medicine
Kayoko Sugita: Keio University School of Medicine
Martin Stražar: Broad Institute of MIT and Harvard
Julian Avila-Pacheco: Broad Institute of MIT and Harvard
Kerry Pierce: Broad Institute of MIT and Harvard
Clary B. Clish: Broad Institute of MIT and Harvard
Ashwin N. Skelly: Keio University School of Medicine
Masahira Hattori: RIKEN Center for Integrative Medical Sciences
Nobuhiro Nakamoto: Keio University School of Medicine
Silvia Caballero: Vedanta Biosciences
Jason M. Norman: Vedanta Biosciences
Bernat Olle: Vedanta Biosciences
Takeshi Tanoue: Keio University School of Medicine
Wataru Suda: RIKEN Center for Integrative Medical Sciences
Makoto Arita: RIKEN Center for Integrative Medical Sciences
Vanni Bucci: UMass Chan Medical School
Koji Atarashi: Keio University School of Medicine
Ramnik J. Xavier: Broad Institute of MIT and Harvard
Kenya Honda: Keio University School of Medicine

Nature, 2024, vol. 633, issue 8031, 878-886

Abstract: Abstract Persistent colonization and outgrowth of potentially pathogenic organisms in the intestine can result from long-term antibiotic use or inflammatory conditions, and may perpetuate dysregulated immunity and tissue damage1,2. Gram-negative Enterobacteriaceae gut pathobionts are particularly recalcitrant to conventional antibiotic treatment3,4, although an emerging body of evidence suggests that manipulation of the commensal microbiota may be a practical alternative therapeutic strategy5–7. Here we isolated and down-selected commensal bacterial consortia from stool samples from healthy humans that could strongly and specifically suppress intestinal Enterobacteriaceae. One of the elaborated consortia, comprising 18 commensal strains, effectively controlled ecological niches by regulating gluconate availability, thereby re-establishing colonization resistance and alleviating Klebsiella- and Escherichia-driven intestinal inflammation in mice. Harnessing these activities in the form of live bacterial therapies may represent a promising solution to combat the growing threat of proinflammatory, antimicrobial-resistant Enterobacteriaceae infection.

Date: 2024
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DOI: 10.1038/s41586-024-07960-6

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