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Background <p>Weaning-induced diarrhoea and growth retardation in piglets are associated with impaired intestinal barrier function and decreased levels of colonic short-chain fatty acids (SCFAs). Although SCFA supplementation has been proposed to mitigate these issues, the efficacy and optimal dosage of sodium isobutyrate remain unclear.</p> Results <p>We investigated the effects of sodium isobutyrate supplementation (500, 1,000, 2,000, and 4,000&#xa0;mg/kg diet) on weaned piglets (Duroc × Landrace × Yorkshire, 28 d of age; <i>n</i> = 8). After a 28-d feeding trial, supplementation at 500–2,000&#xa0;mg/kg significantly improved average daily gain and feed efficiency and reduced diarrhoea frequency, with maximal benefits observed at 1,000&#xa0;mg/kg (<i>P</i> &lt; 0.0001). Additionally, 500–1,000&#xa0;mg/kg sodium isobutyrate supplementation increased the apparent digestibility of crude protein, organic matter, and crude fibre (<i>P</i> &lt; 0.05). Serum biochemical parameters were unaffected, although secretory immunoglobulin A (SIgA) levels significantly increased upon supplementation with 500–1,000&#xa0;mg/kg (<i>P</i> &lt; 0.05). 16S rRNA gene sequencing indicated that sodium isobutyrate increased the abundance of beneficial colonic microbiota. The 1,000&#xa0;mg/kg group presented the most pronounced effect, with a significant increase of the relative abundance of <i>Prevotella</i> and the greatest improvement in SCFA concentrations (<i>P</i> &lt; 0.05). Metabolomics revealed elevated levels of colonic indole-3-lactic acid and 3-hydroxybutyrate upon supplementation with 1,000&#xa0;mg/kg (<i>P</i> &lt; 0.05). Transcriptomic analyses indicated activation of protein digestion and absorption pathways, and PI3K-Akt signalling, marked by <i>TSG-6</i> upregulation and the suppression of <i>ISG15</i> and <i>DDIT4</i> expression (<i>P</i> &lt; 0.05). Supplementation with 1,000&#xa0;mg/kg was associated with improved intestinal barrier-related markers, including reduced serum D-lactate, diamine oxidase, and lipopolysaccharide levels, increased tight junction protein expression; activation of G protein-coupled receptors; and inhibition of TLR4/MyD88/NF-κB signalling (<i>P</i> &lt; 0.05), suggesting enhanced barrier function.</p> Conclusions <p>In conclusion, dietary supplementation with 1,000&#xa0;mg/kg sodium isobutyrate was associated with improved intestinal morphology, reduced serum permeability, increased expression of tight junction proteins, and enhanced immune function in weaned piglets, suggesting enhanced colonic barrier function and providing dosage guidance and mechanistic insights for future applications.</p> Graphical Abstract <p></p>

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Dietary supplementation with sodium isobutyrate enhances growth performance and colonic barrier function in weaned piglets via microbiota-metabolite-host interactions

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月8日

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  • Xiuyu Fang,
  • Zihan Chi,
  • Zhengyi Wang,
  • Xinlin Wang,
  • Xingrui Qu,
  • Shuang Zhang,
  • Feng Gao,
  • Baoming Shi,
  • Xuan Zhao

摘要

Background

Weaning-induced diarrhoea and growth retardation in piglets are associated with impaired intestinal barrier function and decreased levels of colonic short-chain fatty acids (SCFAs). Although SCFA supplementation has been proposed to mitigate these issues, the efficacy and optimal dosage of sodium isobutyrate remain unclear.

Results

We investigated the effects of sodium isobutyrate supplementation (500, 1,000, 2,000, and 4,000 mg/kg diet) on weaned piglets (Duroc × Landrace × Yorkshire, 28 d of age; n = 8). After a 28-d feeding trial, supplementation at 500–2,000 mg/kg significantly improved average daily gain and feed efficiency and reduced diarrhoea frequency, with maximal benefits observed at 1,000 mg/kg (P < 0.0001). Additionally, 500–1,000 mg/kg sodium isobutyrate supplementation increased the apparent digestibility of crude protein, organic matter, and crude fibre (P < 0.05). Serum biochemical parameters were unaffected, although secretory immunoglobulin A (SIgA) levels significantly increased upon supplementation with 500–1,000 mg/kg (P < 0.05). 16S rRNA gene sequencing indicated that sodium isobutyrate increased the abundance of beneficial colonic microbiota. The 1,000 mg/kg group presented the most pronounced effect, with a significant increase of the relative abundance of Prevotella and the greatest improvement in SCFA concentrations (P < 0.05). Metabolomics revealed elevated levels of colonic indole-3-lactic acid and 3-hydroxybutyrate upon supplementation with 1,000 mg/kg (P < 0.05). Transcriptomic analyses indicated activation of protein digestion and absorption pathways, and PI3K-Akt signalling, marked by TSG-6 upregulation and the suppression of ISG15 and DDIT4 expression (P < 0.05). Supplementation with 1,000 mg/kg was associated with improved intestinal barrier-related markers, including reduced serum D-lactate, diamine oxidase, and lipopolysaccharide levels, increased tight junction protein expression; activation of G protein-coupled receptors; and inhibition of TLR4/MyD88/NF-κB signalling (P < 0.05), suggesting enhanced barrier function.

Conclusions

In conclusion, dietary supplementation with 1,000 mg/kg sodium isobutyrate was associated with improved intestinal morphology, reduced serum permeability, increased expression of tight junction proteins, and enhanced immune function in weaned piglets, suggesting enhanced colonic barrier function and providing dosage guidance and mechanistic insights for future applications.

Graphical Abstract