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Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier
Open accessAbstract
AIM: To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. METHODS: Male C57BL/6J mice were divided into three groups, normal control were fed standard chow and model group were fed a high-fat diet (HFD) for 16 wk, the intervention group were fed HFD for 16 wk and treated with NaB for 8 wk. Gut microbiota from each group were detected at baseline and at 16 wk, liver histology were evaluated and gastrointestinal barrier indicator such as zonula occluden-1 (ZO-1) were detected by immunohistochemistry and realtime-PCR, further serum or liver endotoxin were determined by ELISA and inflammation- or metabolism-associated genes were quantified by real-time PCR. RESULTS: . These bacteria can produce butyric acid in what seems like a virtuous circle. And butyrate restored HFD induced intestinal mucosa damage, increased the expression of ZO-1 in small intestine, further decreased the levels of gut endotoxin in serum and liver compared with HF group. Endotoxin-associated genes such as TLR4 and Myd88, pro-inflammation genes such as MCP-1, TNF-α, IL-1, IL-2, IL-6 and IFN-γ in liver or epididymal fat were obviously downregulated after NaB intervention. Liver inflammation and fat accumulation were ameliorated, the levels of TG and cholesterol in liver were decreased after NaB intervention, NAS score was significantly decreased, metabolic indices such as FBG and HOMA-IR and liver function indicators ALT and AST were improved compared with HF group. CONCLUSION: NaB may restore the dysbiosis of gut microbiota to attenuate steatohepatitis, which is suggested to be a potential gut microbiota modulator and therapeutic substance for NAFLD.
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“Zhou et al. reported that sodium butyrate (NaB) reduced the entry of inflammatory factors into the liver by regulating gut microbial dysbiosis, thereby reducing steatohepatitis induced by a high-fat diet [21].”
From Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson’s Disease (2023) · cites this paper as [21]
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Blaak, E. E., Canfora, E. E., Theis, S., Frost, G., Groen, A. K., Mithieux, G., Nauta, A., Scott, K., Stahl, B., van Harsselaar, J., et al. (2020) · Beneficial Microbes · doi:10.3920/bm2020.0057 · Cited by 1,103
Short-chain fatty acids in diseases
Zhang, D., Jian, Y., Zhang, Y., Li, Y., Gu, L.-T., Sun, H.-H., Liu, M., Zhou, H., Wang, Y., & Xu, Z. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01219-9 · Cited by 813
Role of gut microbiota-generated short-chain fatty acids in metabolic and cardiovascular health
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The role of the microbiome in NAFLD and NASH
Kolodziejczyk, A. A., Zheng, D., Shibolet, O., & Elinav, E. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201809302 · Cited by 523
Li, H., Zhou, D.-D., Gan, R., Huang, S., Zhao, C., Shang, A., Xu, X., & Li, H. (2021) · Nutrients · doi:10.3390/nu13093211 · Cited by 514
Self-citation
Metadata
- Authors
- Zhou, D., Pan, Q., Xin, F.-Z., Zhang, R.-N., He, C.-X., Chen, G.-Y., Liu, C., Chen, Y.-W., & Fan, J.-G.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Venue
- World Journal of Gastroenterology
- Publisher
- Baishideng Publishing Group Inc.
- Published
- 2017
- Volume
- 23
- Issue
- 1
- Pages
- 60
- ISSN
- 1007-9327 (ISSN-L)
- PMC
- PMC5221287
- OpenAlex
- W2571212804
- Cited by
- 441
- References
- 56
- Citations by year
- 2026: 34 · 2025: 61 · 2024: 66 · 2023: 58 · 2022: 68 · 2021: 46 · 2020: 50 · 2019: 30 · 2018: 17 · 2017: 11
- FWCI
- 12.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- World Journal of Gastroenterology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- sodium butyrate, non-alcoholic fatty liver disease, steatohepatitis, high-fat diet, gut microbiota, intestinal barrier, zonula occludens-1, endotoxin, gut-liver axis, gut dysbiosis, inflammation, insulin resistance, butyrate
- MeSH terms
- Gastrointestinal Microbiome, Animals, Drug Evaluation, Preclinical, Humans, Immunohistochemistry, Inflammation, Intestinal Mucosa, Lactobacillus, Liver, Liver Function Tests, Male, Mice, Inbred C57BL, Specific Pathogen-Free Organisms, Tumor Necrosis Factor-alpha, Cytokines, Butyric Acid, Mice, Diet, High-Fat, Real-Time Polymerase Chain Reaction, Zonula Occludens-1 Protein, Dysbiosis, Non-alcoholic Fatty Liver Disease
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