Disentangling microbiota-dependent and -independent impacts of antibiotics on host physiology
5 affiliations
- 1Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
- 2Racah Institute of Physics, The Hebrew University of Jerusalem, Jerusalem, Israel
- 3Rachel and Selim Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel
- 4Analytical Chemistry Laboratory, Tel-Hai College, Kiryat Shmona, Israel
- 5Department of Natural Compounds and Analytical Chemistry, MIGAL Galilee Research Institute, Kiryat Shmona, Israel
Abstract
Antibiotics are believed to affect host physiology by altering the gut microbiota. However, it remains unclear which effects of antibiotics are microbiota dependent and which are microbiota independent. Here we present a resource encompassing host and microbiota responses to antibiotic treatment and a computational tool with which to analyse them. Metagenomic and transcriptomic analyses of conventional and germ-free mice revealed that antibiotic administration routes and their combinations affect host and microbiota responses. We developed CompoRes—a computational tool that distinguishes the microbiota-independent impact of antibiotic-induced perturbations, revealing that antibiotics directly impact host physiology. We found that diurnal expression of major histocompatibility complex class II in the mouse colon is controlled by glucose via feeding. This pattern was lost during antibiotic treatment as vancomycin altered feeding behaviour in a microbiota-independent and evolutionarily conserved manner. Together, our study establishes a direct, non-microbial pathway by which antibiotics reshape host immunity and circadian physiology.
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BibTeX
@article{zelik2026disentangling,
title = {{Disentangling microbiota-dependent and -independent impacts of antibiotics on host physiology}},
author = {Lilach Zelik and Yehonatan Levin and Jasmin Sawaed and Shahar Telpaz and Mor Zigdon and Meital Nuriel-Ohayon and Elad Rubin and Ateret Gordon and Zheniya Mogilevski and Amit Yehuda and Aya Awad and Hanaa Shaalan and Shira Ben-Simon and Sonia Modilevsky and Maria Naama and Jay Dalvi and Lelyan Moadi and Marina Kurtz and Shira Perez and Sondra Turjeman and Michal Werbner and Soliman Khatib and Omry Koren and Amir Erez and Shai Bel},
journal = {Nature Microbiology},
year = {2026},
month = oct,
doi = {10.1038/s41564-026-02453-w},
url = {https://doi.org/10.1038/s41564-026-02453-w},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Disentangling microbiota-dependent and -independent impacts of antibiotics on host physiology
AU - Lilach Zelik
AU - Yehonatan Levin
AU - Jasmin Sawaed
AU - Shahar Telpaz
AU - Mor Zigdon
AU - Meital Nuriel-Ohayon
AU - Elad Rubin
AU - Ateret Gordon
AU - Zheniya Mogilevski
AU - Amit Yehuda
AU - Aya Awad
AU - Hanaa Shaalan
AU - Shira Ben-Simon
AU - Sonia Modilevsky
AU - Maria Naama
AU - Jay Dalvi
AU - Lelyan Moadi
AU - Marina Kurtz
AU - Shira Perez
AU - Sondra Turjeman
AU - Michal Werbner
AU - Soliman Khatib
AU - Omry Koren
AU - Amir Erez
AU - Shai Bel
PY - 2026
DA - 2026/10/19
JO - Nature Microbiology
DO - 10.1038/s41564-026-02453-w
UR - https://doi.org/10.1038/s41564-026-02453-w
AB - Antibiotics are believed to affect host physiology by altering the gut microbiota. However, it remains unclear which effects of antibiotics are microbiota dependent and which are microbiota independent. Here we present a resource encompassing host and microbiota responses to antibiotic treatment and a computational tool with which to analyse them. Metagenomic and transcriptomic analyses of conventional and germ-free mice revealed that antibiotic administration routes and their combinations affect host and microbiota responses. We developed CompoRes—a computational tool that distinguishes the microbiota-independent impact of antibiotic-induced perturbations, revealing that antibiotics directly impact host physiology. We found that diurnal expression of major histocompatibility complex class II in the mouse colon is controlled by glucose via feeding. This pattern was lost during antibiotic treatment as vancomycin altered feeding behaviour in a microbiota-independent and evolutionarily conserved manner. Together, our study establishes a direct, non-microbial pathway by which antibiotics reshape host immunity and circadian physiology.
SN - 2058-5276
ER -