Journal article
Antibiotics cause metabolic changes in mice primarily through microbiome modulation rather than behavioral changes
PloS one, Vol.17(3), pp.e0265023-e0265023
03/17/2022
DOI: 10.1371/journal.pone.0265023
PMCID: PMC8929607
PMID: 35298489
Abstract
The microbiome is an important and increasingly-studied mediator of organismal metabolism, although how the microbiome affects metabolism remains incompletely understood. Many investigators use antibiotics to experimentally perturb the microbiome. However, antibiotics have poorly understood yet profound off-target effects on behavior and diet, including food and water aversion, that can confound experiments and limit their applicability. We thus sought to determine the relative influence of microbiome modulation and off-target antibiotic effects on the behavior and metabolic activity of mice.
Mice treated with oral antibiotics via drinking water exhibited significant weight loss in fat, liver, and muscle tissue. These mice also exhibited a reduction in water and food consumption, with marked variability across antibiotic regimens. While administration of bitter-tasting but antimicrobially-inert compounds caused a similar reduction in water consumption, this did not cause tissue weight loss or reduced food consumption. Mice administered intraperitoneal antibiotics (bypassing the gastrointestinal tract) exhibited reduced tissue weights and oral intake, comparable to the effects of oral antibiotics. Antibiotic-treated germ-free mice did not have reduced tissue weights, providing further evidence that direct microbiome modulation (rather than behavioral effects) mediates these metabolic changes.
While oral antibiotics cause profound effects on food and water consumption, antibiotic effects on organismal metabolism are primarily mediated by microbiome modulation. We demonstrate that tissue-specific weight loss following antibiotic administration is due primarily to microbiome effects rather than food and water aversion, and identify antibiotic regimens that effectively modulate gut microbiota while minimizing off-target behavioral effects.
Details
- Title: Subtitle
- Antibiotics cause metabolic changes in mice primarily through microbiome modulation rather than behavioral changes
- Creators
- Kale S Bongers - Michigan MedicineRoderick A McDonald - Michigan MedicineKatherine M Winner - Michigan MedicineNicole R Falkowski - Michigan MedicineChristopher A Brown - Michigan MedicineJennifer M Baker - Michigan MedicineKevin J Hinkle - Michigan MedicineDaniel J Fergle - Michigan MedicineRobert P Dickson - Michigan Medicine
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.17(3), pp.e0265023-e0265023
- Publisher
- PUBLIC LIBRARY SCIENCE; SAN FRANCISCO
- DOI
- 10.1371/journal.pone.0265023
- PMID
- 35298489
- PMCID
- PMC8929607
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Grant note
- F31 HL158033 / NHLBI NIH HHS T32 AI007528 / NIAID NIH HHS R01 HL144599 / NHLBI NIH HHS T32 HL007749 / NHLBI NIH HHS
- Language
- English
- Date published
- 03/17/2022
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984696752302771
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