Antibiotic-induced microbiome depletion alters metabolic homeostasis by affecting gut signaling and colonic metabolism
Open accessAbstract
Antibiotic-induced microbiome depletion (AIMD) has been used frequently to study the role of the gut microbiome in pathological conditions. However, unlike germ-free mice, the effects of AIMD on host metabolism remain incompletely understood. Here we show the effects of AIMD to elucidate its effects on gut homeostasis, luminal signaling, and metabolism. We demonstrate that AIMD, which decreases luminal Firmicutes and Bacteroidetes species, decreases baseline serum glucose levels, reduces glucose surge in a tolerance test, and improves insulin sensitivity without altering adiposity. These changes occur in the setting of decreased luminal short-chain fatty acids (SCFAs), especially butyrate, and the secondary bile acid pool, which affects whole-body bile acid metabolism. In mice, AIMD alters cecal gene expression and gut glucagon-like peptide 1 signaling. Extensive tissue remodeling and decreased availability of SCFAs shift colonocyte metabolism toward glucose utilization. We suggest that AIMD alters glucose homeostasis by potentially shifting colonocyte energy utilization from SCFAs to glucose.
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Secondary bile acid concentrations are significantly higher in the intestines and fecal samples of SPF mice compared with GF mice, providing strong evidence for their microbial origin.
“This phenomenon is evidenced by the significantly higher concentration of secondary BAs in the intestines and fecal samples of SPF mice compared to GF mice, providing strong evidence for their microbial origin.351–353”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [353]
Previous studies have described that successful FMT treatment of recurrent infection by C. difficile relies on restoration of correct bile acid metabolism, and that antibiotic-induced microbiome depletion reduces the secondary bile acid pool.
“Previous studies have described that successful FMT treatment of recurrent infection by C. difficile relies on restoration of correct bile acid metabolism 35,36 , and that antibioticinduced microbiome depletion reduces the secondary bile acid pool 37 .”
From Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice (2019) · cites this paper as [37]
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- Authors
- Zarrinpar, A., Chaix, A., Xu, Z. Z., Chang, M. W., Marotz, C. A., Saghatelian, A., Knight, R., & Panda, S.
- Affiliations
- Salk Institute for Biological Studies (US)
- University of California San Diego (US)
- Corresponding author
- Zarrinpar, Amir
- Panda, Satchidananda
- ORCID
- Venue
- Nature Communications
- Published
- 2018-07-20
- Volume
- 9
- Issue
- 1
- Pages
- 2872-2872
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6054678
- OpenAlex
- W2884737885
- Cited by
- 546
- References
- 51
- Citations by year
- 2026: 58 · 2025: 71 · 2024: 73 · 2023: 70 · 2022: 99 · 2021: 80 · 2020: 60 · 2019: 33 · 2018: 2
- FWCI
- 15.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- American Diabetes Association (CA014195)
- American Heart Association (18CDA34110292, 16BGIA27760160)
- Glenn Foundation for Medical Research (P30 CA014195, P30 EY019005)
- American Association for the Study of Liver Diseases
- Leona M. and Harry B. Helmsley Charitable Trust (#2012-PG-MED002, MED002, 2012-PG)
- University of Michigan (DK097153, U24 DK097153)
- American Gastroenterological Association (DK080506)
- National Institutes of Health (KL2TR000099, TL1TR001443, NIH-R01, NIH R03, UL1TR001442, GM085764, CA014195, DK097153, DK080506)
- National Eye Institute (P30EY019005)
- National Cancer Institute (P30CA014195)
- National Institute of General Medical Sciences (P50GM085764)
- National Institute of Diabetes and Digestive and Kidney Diseases (R24DK080506, R03DK114536, U24DK097153, R01DK091618, R01DK115214, K08DK102902, T32DK007202)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Keywords
- gut microbiota, glucose homeostasis, insulin sensitivity, short-chain fatty acids, butyrate, bile acids, bile acid metabolism, colonic metabolism, Firmicutes, Bacteroidetes, germ-free mice
- MeSH terms
- Gastrointestinal Microbiome, Amphotericin B, Ampicillin, Animals, Anti-Bacterial Agents, Bile Acids and Salts, Blood Glucose, Body Composition, Body Weight, Cecum, Colon, Fatty Acids, Volatile, Gene Expression Regulation, Glucose, Homeostasis, Insulin, Insulin Resistance, Male, Metronidazole, Mice, Inbred C57BL, Neomycin, Obesity, RNA, Ribosomal, 16S, Vancomycin, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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