ArticleCell host & microbe2023
An early-life microbiota metabolite protects against obesity by regulating intestinal lipid metabolism.
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Article in Cell host & microbe, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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71citing papers in PubMed, 1 pooled it
14.3field-weighted citation impact, top 1% of its field
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Effects of Exercise on Gut Microbiota of Adults: A Systematic Review and Meta-Analysis.Nutrients · 2024Pooled it
- Immunometabolism and rheumatic disease-advancing targeted therapies.EULAR rheumatology open · 2026Review
- Extracellular Vesicle-Encapsulated Small RNAs From Clostridium Butyricum Modulate Host Intestinal Lipid Metabolism.Journal of extracellular vesicles · 2026Article
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- Effects of phenylalanine supplementation on meat fatty acid composition, gut microbiota, and pork volatile organic compound profile in finishing pigs.Journal of animal science and biotechnology · 2026Article
- Oxidative Stress as a Pathophysiological Core of Obesity: Preclinical Evidence for Antioxidant-Based Therapy Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
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- Thiazolidinedione Use and Risk of Bacterial Enteric Infection Among Adults With Type 2 Diabetes Mellitus.Open forum infectious diseases · 2026Article
- Treatment with saponins fromNutrition research and practice · 2026Article
- Intestinal cGAS-STING-IFN signalling promotes obesity by downregulating microbiota-derived IAA in male mice.Nature metabolism · 2026Article
- Complementary Protective Effects of Lactiplantibacillus Plantarum GUANKE and Picolinic Acid Against Influenza A Virus Infection in Mice.Probiotics and antimicrobial proteins · 2026Article
- Integrating host-microbiota metabolic networks: how aromatic amino acids shape immune homeostasis and affect disease progression.Cellular & molecular immunology · 2026Review
- Small intestine microbiota development prevents early-life adiposity via IL-22-mediated intestinal PPARα suppression.bioRxiv : the preprint server for biology · 2026Article
- Rational engineering of facultative anaerobiosis enables commensal survival in the oxygenated gut.bioRxiv : the preprint server for biology · 2026Article
- Modulation of the gut microbiome-adipose tissue AXIS by maqui supplementation improved insulin resistance and lipid metabolism in mice under a high-fat diet.Food chemistry. Molecular sciences · 2026Article
- Integrated multi-omics implicates the gut microbiota and bilirubin in abdominal fat deposition in Huainan yellow chickens.Poultry science · 2026Article
- Metabotherapy for intestinal disease: using metabolites to prevent and treat disorders of the gut.Nature reviews. Gastroenterology & hepatology · 2026Review
- Phenyllactic Acid Restores Intestinal Epithelial Barrier to Alleviate Hypertriglyceridemic Acute Pancreatitis via a PPARγ-Dependent Mechanism.Antioxidants (Basel, Switzerland) · 2026Article
- Live and heat-treatediScience · 2026Article
- Aspartate aminotransferase is required forInfection and immunity · 2026Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 6 institutions in 3 countries.
Catherine D SheltonDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Elizabeth SingDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Jessica MoDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Nicolas G ShealyDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Woongjae YooDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
Julia ThomasDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Gillian N FitzDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Pollyana R CastroDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo 12083-862, Brazil.
Tara T HickmanDepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Teresa P TorresDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Nora J FoegedingDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Jacob K ZiebaDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
M Wade CalcuttMass Spectrometry Research Center and Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Simona G CodreanuCenter for Innovative Technology and Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA.
Stacy D SherrodCenter for Innovative Technology and Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA.
John A McLeanCenter for Innovative Technology and Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA.
Sun H PeckDepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Biomedical Engineering, Vanderbilt University School of Engineering, Nashville, TN 37232, USA; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Fan YangDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Nicholas O MarkhamDepartment of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Institute of Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Min LiuDepartment of Pathology and Molecular Medicine, Metabolic Diseases Institute, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
Mariana X ByndlossDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute of Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Digestive Disease Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Microbiome Innovation Center, Vanderbilt University, Nashville, TN 37235, USA; Howard Hughes Medical Institute, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: mariana.x.byndloss@vumc.org.
Vanderbilt University Medical Center · USVanderbilt University · USPohang University of Science and Technology · KRUniversidade Estadual de Campinas (UNICAMP) · BRUniversity of Cincinnati Medical Center · USVA Tennessee Valley Healthcare System · US
Funding
Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8MTranslational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9MVanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ALVIN C POWERS · 2012 to 2026
$29.3MShop Module CoreP30EY008126 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI David J. Calkins · 1989 to 2026
$19.6MTRAINING PROGRAM IN ENVIRONMENTAL TOXICOLOGYT32ES007028 · NIEHS · VANDERBILT UNIVERSITY · PI F PETER Guengerich, Fiona Edith Harrison · 1985 to 2026
$15.7MVanderbilt Mouse Metabolic Physiology CenterU24DK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2001 to 2015
$14.9MTRAINING IN GASTROENTEROLOGYT32DK007673 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 1992 to 2026
$8.4MChemical Biology of Infectious Diseases (CBID) Training ProgramT32AI112541 · NIAID · VANDERBILT UNIVERSITY · PI Eric P Skaar · 2015 to 2026
$4.0MMechanisms of Salmonella-mediated disruption of colonization resistance in the inflamed gutR01AI168302 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Mariana Xavier Byndloss · 2022 to 2026
$2.4MObesogenic diet-induced intestinal epithelium repair responses link dysbiosis and cardiovascular diseaseR01DK131104 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Mariana Xavier Byndloss · 2022 to 2026
$2.4MIllumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600kLSM880-Airyscan Confocal Microscope for Large Shared ResourceS10OD021630 · OD · VANDERBILT UNIVERSITY · PI WELLS, K. SAM · 2016 to 2016
$560kBLRD VA IK2 BX005401BLRD VA IK2 BX005699NCI NIH HHS P30 CA068485NEI NIH HHS P30 EY008126NIAID NIH HHS F31 AI161882NIAID NIH HHS R01 AI168302NIAID NIH HHS T32 AI112541NIDDK NIH HHS P30 DK020593NIDDK NIH HHS P30 DK058404NIDDK NIH HHS R01 DK131104NIDDK NIH HHS T32 DK007673NIDDK NIH HHS U24 DK059637NIEHS NIH HHS T32 ES007028NIH HHS S10 OD021630NIH HHS S10 OD023475NIH HHS S10 OD026929
Abstract
The mechanisms by which the early-life microbiota protects against environmental factors that promote childhood obesity remain largely unknown. Using a mouse model in which young mice are simultaneously exposed to antibiotics and a high-fat (HF) diet, we show that Lactobacillus species, predominant members of the small intestine (SI) microbiota, regulate intestinal epithelial cells (IECs) to limit diet-induced obesity during early life. A Lactobacillus-derived metabolite, phenyllactic acid (PLA), protects against metabolic dysfunction caused by early-life exposure to antibiotics and a HF diet by increasing the abundance of peroxisome proliferator-activated receptor γ (PPAR-γ) in SI IECs. Therefore, PLA is a microbiota-derived metabolite that activates protective pathways in the small intestinal epithelium to regulate intestinal lipid metabolism and prevent antibiotic-associated obesity during early life.
Indexed as
MicrobiotaPediatric ObesityAnimalsAnti-Bacterial AgentsChildDiet, High-FatHumansLipid MetabolismMiceMice, Inbred C57BLPolyestersAnti-Bacterial AgentsPolyestersantibioticsarachnoid barrierbrain fibroblastsearly-lifeintestinal epitheliumLactobacillusleptomeningesmetabolismmicrobiotaobesitysingle-cell RNA sequencingtricellular junction
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