Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features

Niv Zmora, Gili Zilberman-Schapira, Jotham Suez, Uria Mor, Mally Dori-Bachash, Stavros Bashiardes, Eran Kotler, Maya Zur, Dana Regev-Lehavi, Rotem Ben Zeev Brik, Sara Federici, Yotam Cohen, Raquel Linevsky, Daphna Rothschild, Andreas E. Moor, Shani Ben-Moshe, Alon Harmelin, Shalev Itzkovitz, Nitsan Maharshak, Oren ShiboletHagit Shapiro, Meirav Pevsner-Fischer, Itai Sharon, Zamir Halpern*, Eran Segal, Eran Elinav

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Empiric probiotics are commonly consumed by healthy individuals as means of life quality improvement and disease prevention. However, evidence of probiotic gut mucosal colonization efficacy remains sparse and controversial. We metagenomically characterized the murine and human mucosal-associated gastrointestinal microbiome and found it to only partially correlate with stool microbiome. A sequential invasive multi-omics measurement at baseline and during consumption of an 11-strain probiotic combination or placebo demonstrated that probiotics remain viable upon gastrointestinal passage. In colonized, but not germ-free mice, probiotics encountered a marked mucosal colonization resistance. In contrast, humans featured person-, region- and strain-specific mucosal colonization patterns, hallmarked by predictive baseline host and microbiome features, but indistinguishable by probiotics presence in stool. Consequently, probiotics induced a transient, individualized impact on mucosal community structure and gut transcriptome. Collectively, empiric probiotics supplementation may be limited in universally and persistently impacting the gut mucosa, meriting development of new personalized probiotic approaches. Probiotics transiently colonize the human gut mucosa in highly individualized patterns, thereby differentially impacting the indigenous microbiome and host gene-expression profile, a trait which is predictable by baseline host and microbiome features, but not by stool shedding.

Original languageEnglish
Pages (from-to)1388-1405.e21
JournalCell
Volume174
Issue number6
DOIs
StatePublished - 6 Sep 2018

Funding

FundersFunder number
Crown Endowment Fund for Immunological Research
European Foundation
Gurwin Family Fund for Scientific Research
Howard Hughes Medical Institute
Bill and Melinda Gates Foundation
Achelis Foundation
Gilead Sciences
Leona M. and Harry B. Helmsley Charitable Trust
Canadian Institute for Advanced Research
College of Natural Resources and Sciences, Humboldt State University
European Research Council
European Foundation for the Study of Diabetes
Minerva Foundation
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung171548, 171562
Weizmann Institute of Science
German-Israeli Foundation for Scientific Research and Development
Else Kröner-Fresenius-Stiftung
Israel Science Foundation
Centre National de la Recherche Scientifique
Abisch-Frenkel-Stiftung
Helmholtz Association
Crown Human Genome Center
Rising Tide Foundation
Benoziyo Endowment Fund for the Advancement of Science

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