Lactoferrin Modulates Intestinal Morphology and Microbiota Homeostasis in Chronic Social Defeat Stress Mice
6 affiliations
- 1Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, Poland
- 2Doctoral School of Translational Medicine, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, Poland
- 3Department of Animal Nutrition, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3, 05-110 Jabłonna, Poland
- 4Department of Immunopathology, Infectious and Parasitic Diseases, Medical University of Warsaw, Pawińskiego 3c, 02-106 Warsaw, Poland
- 5Department of Physical Chemistry, Medical University of Białystok, Kilińskiego 1, 15-089 Białystok, Poland
- 6Department of Medical Genetics, Medical University of Warsaw, Pawińskiego 3c, 02-106 Warsaw, Poland
Abstract
Chronic social stress is increasingly linked to gut–brain axis dysfunction, yet gut-targeted interventions remain underexplored. This study investigated whether oral lactoferrin (L) administration modulates the intestinal and behavioral consequences of chronic social defeat stress (CSDS) in male C57BL/6J mice. Animals were randomly assigned to four groups—Control, Control+L, CSDS, and CSDS+L—and received lactoferrin (5 mg/kg/day) or vehicle via oral gavage over 15 days concurrent with the CSDS paradigm. Behavioral assessments (fur condition scoring, splash test, open field test), intestinal permeability (FITC-dextran assay), whole gut transit, small-intestine morphology and tight junction protein expression (ZO-1, claudin-5), gut microbiota composition (16S rRNA gene sequencing), and oxidative DNA damage repair activity were evaluated. CSDS induced significant fur deterioration, body weight loss, and reduced grooming behavior, all of which were partially attenuated by L supplementation. In the ileum, CSDS increased crypt number and trended toward decreased claudin-5 expression, whereas L treatment increased crypt depth relative to stressed controls. Although alpha and beta diversity remained unchanged, CSDS prevented the physiological decline of the Firmicutes-to-Bacteroidetes ratio observed in controls, was associated with differences in gut microbiota composition, and L partially restored this trajectory. DNA repair enzyme activities were unaffected. These findings indicate that L mitigates stress-induced somatic deterioration and intestinal alterations, positioning it as a promising gut-targeted nutritional adjunct for stress-related disorders.
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BibTeX
@article{orzelgajowik2026lactoferrin,
title = {{Lactoferrin Modulates Intestinal Morphology and Microbiota Homeostasis in Chronic Social Defeat Stress Mice}},
author = {Karolina Orzeł-Gajowik and Mariusz Popek and Zuzanna Sulej and Marta Obara-Michlewska and Paweł Kowalczyk and Iwona Bukowska-Ośko and Karol Perlejewski and Karol Kramkowski and Agnieszka Pollak and Magdalena Zielińska},
journal = {Molecules},
year = {2026},
month = oct,
doi = {10.3390/molecules31203614},
url = {https://www.mdpi.com/1420-3049/31/20/3614},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Lactoferrin Modulates Intestinal Morphology and Microbiota Homeostasis in Chronic Social Defeat Stress Mice
AU - Karolina Orzeł-Gajowik
AU - Mariusz Popek
AU - Zuzanna Sulej
AU - Marta Obara-Michlewska
AU - Paweł Kowalczyk
AU - Iwona Bukowska-Ośko
AU - Karol Perlejewski
AU - Karol Kramkowski
AU - Agnieszka Pollak
AU - Magdalena Zielińska
PY - 2026
DA - 2026/10/01
JO - Molecules
DO - 10.3390/molecules31203614
UR - https://www.mdpi.com/1420-3049/31/20/3614
AB - Chronic social stress is increasingly linked to gut–brain axis dysfunction, yet gut-targeted interventions remain underexplored. This study investigated whether oral lactoferrin (L) administration modulates the intestinal and behavioral consequences of chronic social defeat stress (CSDS) in male C57BL/6J mice. Animals were randomly assigned to four groups—Control, Control+L, CSDS, and CSDS+L—and received lactoferrin (5 mg/kg/day) or vehicle via oral gavage over 15 days concurrent with the CSDS paradigm. Behavioral assessments (fur condition scoring, splash test, open field test), intestinal permeability (FITC-dextran assay), whole gut transit, small-intestine morphology and tight junction protein expression (ZO-1, claudin-5), gut microbiota composition (16S rRNA gene sequencing), and oxidative DNA damage repair activity were evaluated. CSDS induced significant fur deterioration, body weight loss, and reduced grooming behavior, all of which were partially attenuated by L supplementation. In the ileum, CSDS increased crypt number and trended toward decreased claudin-5 expression, whereas L treatment increased crypt depth relative to stressed controls. Although alpha and beta diversity remained unchanged, CSDS prevented the physiological decline of the Firmicutes-to-Bacteroidetes ratio observed in controls, was associated with differences in gut microbiota composition, and L partially restored this trajectory. DNA repair enzyme activities were unaffected. These findings indicate that L mitigates stress-induced somatic deterioration and intestinal alterations, positioning it as a promising gut-targeted nutritional adjunct for stress-related disorders.
SN - 1420-3049
ER -