Long-Term Sucralose Consumption Alters Gut Microbiota and Hepatic Lipid Metabolism and Increases Depressive-like Behavior in Young Mice
- 1Department of Food and Nutrition, Chungnam National University, Daejeon 34134, Republic of Korea
- 2Glocal Lifecare Convergence Program, Interdisciplinary Education Center for the Innovative Next Generation Leaders in Glocal Lifecare, Chungnam National University, Daehak-ro 99, Yuseong-gu, Daejeon 34134, Republic of Korea
- 3Research Center for Microbiome-Brain Disorders, Chungnam National University, Daejeon 34134, Republic of Korea
Abstract
Background: Sucralose is widely used as a non-nutritive sweetener, yet its systemic consequences of long-term exposure remain incompletely understood. This study investigated the effects of long-term sucralose consumption on metabolic homeostasis and neurobehavioral outcomes. Methods: Male C57BL/6J mice were treated with 5 mg/kg body weight sucralose under non-stressed and unpredictable chronic mild stress conditions for 14 weeks. Results: Sucralose altered hepatic cholesterol regulation without significantly increasing serum triglyceride or total cholesterol relative to water controls. Significant treatment–stress interactions were detected for hepatic Srb1 (F = 6.511, p = 0.004) and intestinal Npc1l1 (F = 3.763, p = 0.032), indicating stress-dependent modulation of cholesterol absorption. Hepatic inflammation also showed significant interactions for Il6 (p < 0.001) and Tnfa (p = 0.003). In addition, the sucralose group exhibited heightened neuroinflammation, cerebral endoplasmic reticulum stress, and increased depressive-like behaviors. 16S rRNA sequencing demonstrated reduced α-diversity and a shift in microbial composition and predicted carbohydrate processing and transport functions. Spearman correlation analysis linked microbial, intestinal, hepatic, neuroinflammatory, and behavioral variables within sucralose-treated mice. Conclusions: Long-term sucralose consumption altered gut microbial composition, hepatic cholesterol regulation, and neuroinflammatory and behavioral outcomes.
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BibTeX
@article{ortutu2026longterm,
title = {{Long-Term Sucralose Consumption Alters Gut Microbiota and Hepatic Lipid Metabolism and Increases Depressive-like Behavior in Young Mice}},
author = {Beulah Favour Ortutu and Kyeong-sook Keum and Jin Gyeom Kim and Su-In Yoon and Jin Ah Cho},
journal = {Nutrients},
year = {2026},
month = oct,
doi = {10.3390/nu18203452},
url = {https://www.mdpi.com/2072-6643/18/20/3452},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Long-Term Sucralose Consumption Alters Gut Microbiota and Hepatic Lipid Metabolism and Increases Depressive-like Behavior in Young Mice
AU - Beulah Favour Ortutu
AU - Kyeong-sook Keum
AU - Jin Gyeom Kim
AU - Su-In Yoon
AU - Jin Ah Cho
PY - 2026
DA - 2026/10/01
JO - Nutrients
DO - 10.3390/nu18203452
UR - https://www.mdpi.com/2072-6643/18/20/3452
AB - Background: Sucralose is widely used as a non-nutritive sweetener, yet its systemic consequences of long-term exposure remain incompletely understood. This study investigated the effects of long-term sucralose consumption on metabolic homeostasis and neurobehavioral outcomes. Methods: Male C57BL/6J mice were treated with 5 mg/kg body weight sucralose under non-stressed and unpredictable chronic mild stress conditions for 14 weeks. Results: Sucralose altered hepatic cholesterol regulation without significantly increasing serum triglyceride or total cholesterol relative to water controls. Significant treatment–stress interactions were detected for hepatic Srb1 (F = 6.511, p = 0.004) and intestinal Npc1l1 (F = 3.763, p = 0.032), indicating stress-dependent modulation of cholesterol absorption. Hepatic inflammation also showed significant interactions for Il6 (p < 0.001) and Tnfa (p = 0.003). In addition, the sucralose group exhibited heightened neuroinflammation, cerebral endoplasmic reticulum stress, and increased depressive-like behaviors. 16S rRNA sequencing demonstrated reduced α-diversity and a shift in microbial composition and predicted carbohydrate processing and transport functions. Spearman correlation analysis linked microbial, intestinal, hepatic, neuroinflammatory, and behavioral variables within sucralose-treated mice. Conclusions: Long-term sucralose consumption altered gut microbial composition, hepatic cholesterol regulation, and neuroinflammatory and behavioral outcomes.
SN - 2072-6643
ER -