Cited by 291Inflammatory Bowel DiseaseGut microbiota and healthAnimal Nutrition and Physiology

Gut microbiota-derived butyrate regulates gut mucus barrier repair by activating the macrophage/WNT/ERK signaling pathway

Liang, Liping, Liu, Le, Zhou, Wanyan, Yang, Chenghai, Mai, Genghui, Li, Haolin, Chen, Ye·2022·Clinical Science

Abstract

Ulcerative colitis (UC) is majorly associated with dysregulation of the dynamic cross-talk among microbial metabolites, intestinal epithelial cells, and macrophages. Several studies have reported the significant role of butyrate in host–microbiota communication. However, whether butyrate provides anti-inflammatory profiles in macrophages, thus contributing to UC intestinal mucus barrier protection, has currently remained elusive. In the current study, we found that butyrate increased mucin production and the proportion of mucin-secreting goblet cells in the colon crypt in a macrophage-dependent manner by using clodronate liposomes. Furthermore, in vivo and in vitro studies were conducted, validating that butyrate facilitates M2 macrophage polarization with the elevated expressions of CD206 and arginase-1 (Arg1). In macrophages/goblet-like LS174T cells co-culture systems, butyrate-primed M2 macrophages significantly enhanced the expression of mucin-2 (MUC2) and SPDEF (goblet cell marker genes) than butyrate alone, while blockade of WNTs secretion or ERK1/2 activation significantly decreased the beneficial effect of butyrate-primed macrophages on goblet cell function. Additionally, the adoptive transfer of butyrate-induced M2 macrophages facilitated the generation of goblet cells and mucus restoration following dextran sulfate sodium (DSS) insult. Taken together, our results revealed a novel mediator of macrophage–goblet cell cross-talk associated with the regulation of epithelial barrier integrity, implying that the microbial metabolite butyrate may serve as a candidate therapeutic target for UC.

Integrity signals

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Crossref · 10.1042/cs20210778

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  • The beneficial effects of butyrate supplementation on PD pathologies might be attributed to its potent HDAC inhibitory activity and its ability to promote intestinal barrier and BBB integrity.

    “The beneficial effects of butyrate supplementation on PD pathologies might be attributed to its potent HDAC inhibitory activity and its ability to promote intestinal barrier and BBB integrity.336–339”

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Authors
Liang, L., Liu, L., Zhou, W., Yang, C., Mai, G., Li, H., & Chen, Y.
Affiliations
  • Nanfang Hospital (CN)
  • Southern Medical University Shenzhen Hospital (CN)
Corresponding author
Chen, Ye
Venue
Clinical Science
Published
2022-02
Volume
136
Issue
4
Pages
291-307
ISSN
  • 0143-5221 (ISSN-L)
  • 1470-8736
OpenAlex
W4213170708
Cited by
291
References
54
Citations by year
2026: 88 · 2025: 82 · 2024: 68 · 2023: 39 · 2022: 14
FWCI
30.62
Type
journal article
Language
en
Open access
closed
Locations
  • Clinical Science (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
Keywords
butyrate, gut microbiota, ulcerative colitis, goblet cells, MUC2, M2 macrophage polarization, Wnt signaling, ERK signaling, CD206, arginase-1, SPDEF, epithelial barrier integrity, DSS-induced colitis
MeSH terms
Gastrointestinal Microbiome, Animals, Butyrates, Cell Line, Colitis, Ulcerative, Humans, Macrophages, Mice, Inbred BALB C, Case-Control Studies, Adoptive Transfer, Goblet Cells, Mice, Wnt Signaling Pathway

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