ArticleMicrobiome2019
Dietary fructose-induced gut dysbiosis promotes mouse hippocampal neuroinflammation: a benefit of short-chain fatty acids.
Article in Microbiome, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers, 5 of them syntheses that pooled it.
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Who cites it
168 citing papers in PubMed, 5 syntheses or guidelines pooled it, 278 citations in OpenAlex.
- Interactions between Gut Microbiota and Oral Antihyperglycemic Drugs: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Emerging trends and hotspots in intestinal microbiota research in sepsis: bibliometric analysis.Frontiers in medicine · 2024Pooled it
- Gut microbiota bridges dietary nutrients and host immunity.Science China. Life sciences · 2023Pooled it
- Pooled it
- Pooled it
- Overconsumption of fructose aggravates acute GVHD by inducing gut dysbiosis and promoting macrophage-mediated inflammatory response.Gut microbes · 2026Article
- Beyond probiotics and pathobionts: mechanistic roles of enterococcus-derived bioactive components in health and disease.Folia microbiologica · 2026Review
- Dietary Fructose and Early-Onset Colorectal Cancer: Metabolic, Microbial, and Translational Perspectives.Microorganisms · 2026Review
- Dexpanthenol Attenuates High Fructose Corn Syrup-Induced Brain Injury by Modulating Oxidative Stress, Neuroinflammation, Apoptotic Signaling and Amyloidogenic Gene Expression.Molecular neurobiology · 2026Article
- Effects of an Antibiotic Alternative Additive on Growth Performance, Intestinal Histomorphology, Multi-Omics Profiles, and Microbiome-Host Interactions in Tibetan Pigs.Veterinary sciences · 2026Article
- Impact of Coffee Consumption on Fructose-Related Metabolic Alterations: Potential Mechanisms and Implications for Metabolic Diseases.Diseases (Basel, Switzerland) · 2026Review
- Oral hydrogel systems in lower gastrointestinal disorders: From disease-based therapy to microbiota-guided design.Materials today. Bio · 2026Review
- Insomnia: the gut microbiome connection, prospects for probiotic and postbiotic therapies, and future directions.Journal of advanced research · 2026Review
- Sex- and mouse strain-related differences in body weight gain, composition of the gut microbiota, and levels of selected metabolites in response to a Western-style diet.BMC gastroenterology · 2026Article
- Sugar ABC transporter repertoires predict ecological dynamics in gut microbiome communities.Research square · 2026Article
- NLRP6 as a candidate segmental barrier to carcinogenesis in the human gut: a hypothesis.Frontiers in immunology · 2026Review
- Bifidobacterium breve BBr60 Enhances SCFA Levels and Restores NLRP3/NLRP6 Balance in the Gut to Improve Motor Deficits in PD Mice.Probiotics and antimicrobial proteins · 2026Article
- Intestinal mucosal barrier injury: insights from interdisciplinary perspectives and therapeutic approaches.Frontiers in nutrition · 2026Review
- Short-chain fatty acids attenuate sepsis-induced gut dysbiosis and hippocampal neuroinflammation via NLRP6 inflammasome activation in mice.International journal of surgery (London, England) · 2026Article
- Dietary targeting of CNBP to rein in the EREG-EGFR cascade and restore homeostasis in colitis-associated colorectal cancer.International journal of biological sciences · 2026Article
108 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWestern-style diets arouse neuroinflammation and impair emotional and cognitive behavior in humans and animals. Our previous study showed that a high-fructose diet caused the hippocampal neuroinflammatory response and neuronal loss in animals, but the underlying mechanisms remained elusive. Here, alterations in the gut microbiota and intestinal epithelial barrier were investigated as the causes of hippocampal neuroinflammation induced by high-fructose diet.
resultsA high-fructose diet caused the hippocampal neuroinflammatory response, reactive gliosis, and neuronal loss in C57BL/6N mice. Depletion of the gut microbiota using broad-spectrum antibiotics suppressed the hippocampal neuroinflammatory response in fructose-fed mice, but these animals still exhibited neuronal loss. Gut microbiota compositional alteration, short-chain fatty acids (SCFAs) reduction, intestinal epithelial barrier impairment, NOD-like receptor family pyrin domain-containing 6 (NLRP6) inflammasome dysfunction, high levels of serum endotoxin, and FITC-dextran were observed in fructose-fed mice. Of note, SCFAs, as well as pioglitazone (a selective peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist), shaped the gut microbiota and ameliorated intestinal epithelial barrier impairment and NLRP6 inflammasome dysfunction in fructose-fed mice. Moreover, SCFAs-mediated NLRP6 inflammasome activation was inhibited by histamine (a bacterial metabolite) in ex vivo colonic explants and suppressed in murine CT26 colon carcinoma cells transfected with NLRP6 siRNA. However, pioglitazone and GW9662 (a PPAR-γ antagonist) exerted no impact on SCFAs-mediated NLRP6 inflammasome activation in ex vivo colonic explants, suggesting that SCFAs may stimulate NLRP6 inflammasome independently of PPAR-γ activation. SCFAs and pioglitazone prevented fructose-induced hippocampal neuroinflammatory response and neuronal loss in mice. Additionally, SCFAs activated colonic NLRP6 inflammasome and increased DCX
conclusionsOur findings reveal that gut dysbiosis is a critical factor for a high-fructose diet-induced hippocampal neuroinflammation in C57BL/6N mice possibly mediated by impairing intestinal epithelial barrier. Mechanistically, the defective colonic NLRP6 inflammasome is responsible for intestinal epithelial barrier impairment. SCFAs can stimulate NLRP6 inflammasome and ameliorate the impairment of intestinal epithelial barrier, resulting in the protection against a high-fructose diet-induced hippocampal neuroinflammation and neuronal loss. This study addresses a gap in the understanding of neuronal injury associated with Western-style diets. A new intervention strategy for reducing the risk of neurodegenerative diseases through SCFAs supplementation or dietary fiber consumption is emphasized.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.