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

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

Journal: Cell 2019;174(6):1388-1405.e21

PMID: 30193112

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Evidence regarding the efficacy of probiotics in colonising the gut mucosa are sparse. The authors investigated whether probiotics colonise the gut mucosa in mice and humans, using both gut mucosa and stool samples. They found that, in both mice and humans, results from stool samples only partially correlate with colonisation of the gut mucosa as determined through gut mucosa samples. Whilst results were fairly uniform in mice, in humans a person-specific resistance to colonisation of the gut mucosa by probiotics was observed. Inter-person variation could be predicted by the composition of the pre-probiotic microbiome and host immune features.

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.

Copyright © 2018 Elsevier Inc. All rights reserved.

Address: Immunology Department, Weizmann Institute of Science, Rehovot, 7610001, Israel; Internal Medicine Department, Tel Aviv Sourasky Medical Center, Tel Aviv, 6423906, Israel.; Immunology Department, Weizmann Institute of Science, Rehovot, 7610001, Israel.; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 7610001, Israel; Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, 7610001, Israel.; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 7610001, Israel.; Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, 7610001, Israel.; Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv, 6423906, Israel; Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.; Migal Galilee Research Institute, Kiryat Shmona, 11016, Israel; Tel Hai College, Upper Galilee, 1220800, Israel.; Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv, 6423906, Israel; Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel. Electronic address: [email protected].; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 7610001, Israel; Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, 7610001, Israel. Electronic address: [email protected].; Immunology Department, Weizmann Institute of Science, Rehovot, 7610001, Israel. Electronic address: [email protected].

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