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Background <p>Citrulline (Cit), an effective precursor of arginine (Arg), escapes hepatic catabolism to be almost completely absorbed into the systemic circulation, thereby being efficiently converted to Arg in the kidneys to enhance its systemic bioavailability. This study investigated the effects of dietary Cit supplementation on lactation performance in sows, as well as the underlying mechanisms related to intestinal health in their suckling piglets, using multi-omics analyses.</p> Results <p>Dietary Arg and Cit supplementation significantly increased average daily feed intake of lactating sows. Milk fat content and plasma nitric oxide (NO) concentration increased significantly in the Arg group and the 40%Cit group (<i>P</i> &lt; 0.05), while milk threonine content increased slightly (<i>P</i> = 0.084). Consequently, the average daily gain of suckling piglets over the 21-day lactation period was also significantly improved. Furthermore, maternal 40%Cit supplementation improved the intestinal health of offspring by enhancing jejunal morphology and upregulating the expression of the tight junction protein occludin (<i>P</i> &lt; 0.05), indicating a strengthened intestinal barrier. Mechanistically, this was achieved by activating the mTOR/S6 pathway in the piglets' jejunum. Maternal 40%Cit supplementation upregulated the expression of proteins related to mitochondrial fusion and fission (MFN2 and MFF, <i>P</i> &lt; 0.05), and the protein expression of OPA1 showed an increasing trend (<i>P</i> = 0.097), indicating the structural and functional status of mitochondria was improved. Maternal 40%Cit supplementation also modulated the gut microbiota of piglets, increasing the abundance of beneficial bacteria (<i>Lachnoclostridium</i>). Metabolomic analysis of sow milk identified 58 differential metabolites. Among these metabolites, palmitic acid levels were significantly increased and positively correlated with the abundance of <i>Lachnoclostridium</i> in the intestine (<i>P</i> &lt; 0.05).</p> Conclusions <p>Dietary Cit supplementation enhanced sow lactation performance and improved intestinal barrier function in their offspring via activation of the jejunal mTOR/S6 pathway and improved mitochondrial structure and function in the piglet jejunum. These benefits were further supported by modulation of the gut microbiota and alterations in the milk fat and metabolome, ultimately promoting piglet growth.</p> Graphical Abstract <p></p>

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Unraveling the effector mechanism of citrulline on sow lactation and offspring growth: an integrative multi-omics analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月16日

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  • Yating Chen,
  • Shenglan Hu,
  • Yiwen Ji,
  • Fang Gu,
  • Chenyang Zhang,
  • Kaiguo Gao,
  • Xiaolu Wen,
  • Li Wang,
  • Xiaoli Dong,
  • Jisoo Tak,
  • Hao Xiao,
  • Yaoyao Xia

摘要

Background

Citrulline (Cit), an effective precursor of arginine (Arg), escapes hepatic catabolism to be almost completely absorbed into the systemic circulation, thereby being efficiently converted to Arg in the kidneys to enhance its systemic bioavailability. This study investigated the effects of dietary Cit supplementation on lactation performance in sows, as well as the underlying mechanisms related to intestinal health in their suckling piglets, using multi-omics analyses.

Results

Dietary Arg and Cit supplementation significantly increased average daily feed intake of lactating sows. Milk fat content and plasma nitric oxide (NO) concentration increased significantly in the Arg group and the 40%Cit group (P < 0.05), while milk threonine content increased slightly (P = 0.084). Consequently, the average daily gain of suckling piglets over the 21-day lactation period was also significantly improved. Furthermore, maternal 40%Cit supplementation improved the intestinal health of offspring by enhancing jejunal morphology and upregulating the expression of the tight junction protein occludin (P < 0.05), indicating a strengthened intestinal barrier. Mechanistically, this was achieved by activating the mTOR/S6 pathway in the piglets' jejunum. Maternal 40%Cit supplementation upregulated the expression of proteins related to mitochondrial fusion and fission (MFN2 and MFF, P < 0.05), and the protein expression of OPA1 showed an increasing trend (P = 0.097), indicating the structural and functional status of mitochondria was improved. Maternal 40%Cit supplementation also modulated the gut microbiota of piglets, increasing the abundance of beneficial bacteria (Lachnoclostridium). Metabolomic analysis of sow milk identified 58 differential metabolites. Among these metabolites, palmitic acid levels were significantly increased and positively correlated with the abundance of Lachnoclostridium in the intestine (P < 0.05).

Conclusions

Dietary Cit supplementation enhanced sow lactation performance and improved intestinal barrier function in their offspring via activation of the jejunal mTOR/S6 pathway and improved mitochondrial structure and function in the piglet jejunum. These benefits were further supported by modulation of the gut microbiota and alterations in the milk fat and metabolome, ultimately promoting piglet growth.

Graphical Abstract