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. 2024 Jan 3:102:skae140.
doi: 10.1093/jas/skae140.

Dietary supplementation with dihydroartemisinin improves intestinal barrier function in weaned piglets with intrauterine growth retardation by modulating the gut microbiota

Yu Niu  1 , Ruiqiang Zhang  1 , Caimei Yang  1 , Jintian He  2 , Tian Wang  2
Affiliations

Dietary supplementation with dihydroartemisinin improves intestinal barrier function in weaned piglets with intrauterine growth retardation by modulating the gut microbiota

Yu Niu et al. J Anim Sci. .

Abstract

The aim of this study was to investigate whether dietary dihydroartemisinin (DHA) supplementation could improve intestinal barrier function and microbiota composition in intrauterine growth restriction (IUGR) weaned piglets. Twelve normal birth weight (NBW) piglets and 24 IUGR piglets at 21 d of age were divided into three groups, which were fed a basal diet (NBW-CON and IUCR-CON groups) and an 80 mg/kg DHA diet (IUGR-DHA group). At 49 d of age, eight piglets of each group with similar body weights within groups were slaughtered, and serum and small intestine samples were collected. The results showed that IUGR piglets reduced growth performance, impaired the markers of intestinal permeability, induced intestinal inflammation, decreased intestinal immunity, and disturbed the intestinal microflora. Dietary DHA supplementation increased average daily gain, average daily feed intake, and body weight at 49 d of age in IUGR-weaned piglets (P < 0.05). DHA treatment decreased serum diamine oxidase activity and increased the numbers of intestinal goblet cells and intraepithelial lymphocytes, concentrations of jejunal mucin-2 and ileal trefoil factor 3, and intestinal secretory immunoglobin A and immunoglobin G (IgG) concentrations of IUGR piglets (P < 0.05). Diet supplemented with DHA also upregulated mRNA abundances of jejunal IgG, the cluster of differentiation 8 (CD8), major histocompatibility complex-I (MHC-I), and interleukin 6 (IL-6) and ileal IgG, Fc receptor for IgG (FcRn), cluster of differentiation 8 (CD4), CD8, MHC-I, IL-6 and tumor necrosis factor α (TNF-α), and enhanced mRNA abundance and protein expression of intestinal occludin and ileal claudin-1 in IUGR piglets (P < 0.05). In addition, DHA supplementation in the diet improved the microbial diversity of the small intestine of IUGR piglets and significantly increased the relative abundance of Actinobacteriota, Streptococcus, Blautia and Streptococcus in the jejunum, and Clostridium sensu_ stricto_in the ileum (P < 0.05). The intestinal microbiota was correlated with the mRNA abundance of tight junction proteins and inflammatory response-related genes. These data suggested that DHA could improve the markers of intestinal barrier function in IUGR-weaned piglets by modulating gut microbiota. DHA may be a novel nutritional candidate for preventing intestinal dysfunction in IUGR pigs.

Keywords: barrier function; dihydroartemisinin; intestine; intrauterine growth retardation; microbiota; piglet.

Plain language summary

Intrauterine growth retardation (IUGR) is defined as the restricted development of the mammalian fetus or its organs during pregnancy, which has high morbidity and mortality during the perinatal period and improves the risk of metabolic diseases in the long term. Dihydroartemisinin (DHA) is a derivative of artemisinin that possesses anti-inflammatory and immunoregulatory effects. Therefore, this experiment was conducted to investigate whether dietary DHA supplementation could improve the intestinal barrier function and microbiota composition in IUGR-weaned piglets. The result showed that IUGR could lead to intestinal barrier dysfunction. Dietary supplementation with DHA improved growth performance and attenuated intestinal barrier dysfunction by decreasing the markers of intestinal permeability, increasing the mucus layer barrier, enhancing immunity, and reducing the inflammatory response in IUGR piglets, which may be attributed to the improvement of the intestinal microbiota. Moreover, the study indicated that the gut microflora was correlated with the gene expression of tight junction proteins and immune function. This study may provide a new nutritional strategy for the maintenance of intestinal health in IUGR pigs.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1.
Figure 1.
Effect of dietary dihydroartemisinin (DHA) supplementation on the d-lactate (d-LA) concentration (A) and diamine oxidase (DAO) activity (B) in the serum of weaned piglets with intrauterine growth retardation (IUGR). NBW-CON, normal body weight (NBW) weaned piglets fed with basal diet; IUGR-CON, IUGR weaned piglets fed with basal diet. IUGR-DHA, IUGR weaned piglets fed with a basal diet supplemented with 80 mg/kg DHA. Data were presented as mean ± SEM (n = 8). *, a significant difference (P < 0.05) between NBW-CON group and IUGR-CON group; #, a significant difference (P < 0.05) between IUGR-DHA group and IUGR-CON group.
Figure 2.
Figure 2.
Effect of dietary dihydroartemisinin (DHA) supplementation on the numbers of goblet cells (GCs) and intraepithelial lymphocytes (IELs) in the intestine of weaned piglets with intrauterine growth retardation (IUGR). NBW-CON, normal body weight (NBW) weaned piglets fed with basal diet; IUGR-CON, IUGR weaned piglets fed with basal diet. IUGR-DHA, IUGR weaned piglets fed with basal diet supplemented with 80 mg/kg DHA. Data were presented as mean ± SEM (n = 8). *, a significant difference (P < 0.05) between NBW-CON group and IUGR-CON group; #, a significant difference (P < 0.05) between IUGR-DHA group and IUGR-CON group.
Figure 3.
Figure 3.
Effect of dietary dihydroartemisinin (DHA) supplementation on the concentrations of mucin 2 (MUC2) and trefoil factor 3 (TFF3) in the intestine of weaned piglets with intrauterine growth retardation (IUGR). NBW-CON, normal body weight (NBW) weaned piglets fed with basal diet; IUGR-CON, IUGR weaned piglets fed with basal diet. IUGR-DHA, IUGR weaned piglets fed with basal diet supplemented with 80 mg/kg DHA. Data were presented as mean ± SEM (n = 8). *, a significant difference (P < 0.05) between NBW-CON group and IUGR-CON group; #, a significant difference (P < 0.05) between IUGR-DHA group and IUGR-CON group.
Figure 4.
Figure 4.
Effect of dietary dihydroartemisinin (DHA) supplementation on the concentrations of secretory immunoglobulin A (sIgA) and immunoglobulin G (IgG) in the intestine of weaned piglets with intrauterine growth retardation (IUGR). NBW-CON, normal body weight (NBW) weaned piglets fed with basal diet; IUGR-CON, IUGR weaned piglets fed with basal diet. IUGR-DHA, IUGR weaned piglets fed with basal diet supplemented with 80 mg/kg DHA. Data were presented as mean ± SEM (n = 8). *, a significant difference (P < 0.05) between NBW-CON group and IUGR-CON group; #, a significant difference (P < 0.05) between IUGR-DHA group and IUGR-CON group.
Figure 5.
Figure 5.
Effect of dietary dihydroartemisinin (DHA) supplementation on the related mRNA abundance of immune function in the jejunum (A) and ileum (B) of weaned piglets with intrauterine growth retardation (IUGR). NBW-CON, normal body weight (NBW) weaned piglets fed with basal diet; IUGR-CON, IUGR weaned piglets fed with basal diet. IUGR-DHA, IUGR weaned piglets fed with basal diet supplemented with 80 mg/kg DHA. Data were presented as mean ± SEM (n = 8). *, a significant difference (P < 0.05) between NBW-CON group and IUGR-CON group; #, a significant difference (P < 0.05) between IUGR-DHA group and IUGR-CON group.
Figure 6.
Figure 6.
Effect of dietary dihydroartemisinin (DHA) supplementation on the mRNA abundances of tight junction proteins in the jejunum (A) and ileum (B) of weaned piglets with intrauterine growth retardation (IUGR). NBW-CON, normal body weight (NBW) weaned piglets fed with basal diet; IUGR-CON, IUGR weaned piglets fed with basal diet. IUGR-DHA, IUGR weaned piglets fed with basal diet supplemented with 80 mg/kg DHA. Data were presented as mean ± SEM (n = 8). *, a significant difference (P < 0.05) between NBW-CON group and IUGR-CON group; #, a significant difference (P < 0.05) between IUGR-DHA group and IUGR-CON group.
Figure 7.
Figure 7.
Effect of dietary dihydroartemisinin (DHA) supplementation on the protein expressions of claudin-1 (A) and occludin (B) in the jejunum and ileum of weaned piglets with intrauterine growth retardation (IUGR). The bands were the representative Western blot images of claudin-1 (20 kDa), occludin (65 kDa), and β-actin (45 kDa). NBW-CON, normal body weight (NBW) weaned piglets fed with basal diet; IUGR-CON, IUGR weaned piglets fed with basal diet. IUGR-DHA, IUGR weaned piglets fed with basal diet supplemented with 80 mg/kg DHA. Data were presented as mean ± SEM (n = 8). *, a significant difference (P < 0.05) between NBW-CON group and IUGR-CON group; #, a significant difference (P < 0.05) between IUGR-DHA group and IUGR-CON group.
Figure 8.
Figure 8.
Effect of dietary dihydroartemisinin (DHA) supplementation on the jejunal microbiota structure of weaned piglets with intrauterine growth retardation (IUGR). (A-D) Alpha diversity analysis. (E) PCoA analysis based on the Bray-Curtis distance. (F-G) Relative abundance of jejunal microbial communities at the phylum level. (H-K) Relative abundance of jejunal microbial communities at the genus level. (L) The Spearman correlation analysis between jejunal microbiota and mRNA abundance of tight junction proteins and immunity. NC, normal body weight weaned piglets fed with basal diet; IC, IUGR weaned piglets fed with basal diet. ID, IUGR weaned piglets fed with basal diet supplemented with 80 mg/kg DHA. *P < 0.05, **P < 0.01.
Figure 9.
Figure 9.
Effect of dietary dihydroartemisinin (DHA) supplementation on the ileal microbiota structure of weaned piglets with intrauterine growth retardation (IUGR). (A-D) Alpha diversity analysis. (E) PCoA analysis based on the Bray-Curtis distance. (F) Relative abundance of ileal microbial communities at the phylum level. (G-H) Relative abundance of ileal microbial communities at genus level. (I) The Spearman correlation analysis between ileal microbiota and mRNA abundance of tight junction proteins and immunity. NC, normal body weight weaned piglets fed with basal diet; IC, IUGR weaned piglets fed with basal diet. ID, IUGR weaned piglets fed with a basal diet supplemented with 80 mg/kg DHA. *P < 0.05, **P < 0.01.
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References

    1. Ansari, M. T., Iqbal I., and Sunderland V. B... 2009. Dihydroartemisinin-cyclodextrin complexation: solubility and stability. Arch. Pharm. Res. 32:155–165. doi: 10.1007/s12272-009-1130-4 - DOI - PubMed
    1. Bai, K., Jiang L. Y., Li Q. M., Zhang J. F., Zhang L. L., and Wang T... 2021. Dietary dimethylglycine sodium salt supplementation improves growth performance, redox status, and skeletal muscle function of intrauterine growth-restricted weaned piglets. J. Anim. Sci. 99:skb186. doi: 10.1093/jas/skab186 - DOI - PMC - PubMed
    1. Beagley, K. W., Fujihashi K., Lagoo A. S., Lagoo-Deenadaylan S., and Elson C. O... 1995. Differences in intraepithelial lymphocyte T cell subsets isolated from murine small versus large intestine. J. Immunol. 154:5611–5619. doi: 10.1084/jem.181.6.2295 - DOI - PubMed
    1. Bernstein, I. M., Horbar J. D., Badger G. J., Ohlsson A., and Golan A... 2000. Morbidity and mortality among very-low-birth-weight neonates with intrauterine growth restriction. Am. J. Obstet. Gynecol. 182:198–206. doi: 10.1016/s0002-9378(00)70513-8 - DOI - PubMed
    1. Camara-Lemarroy, C. R., Escobedo-Zúñiga N., Guzmán-de la Garza F. J., Castro-Garza J., Vargas-Villarreal J., and Góngora-Rivera F... 2018. D-Lactate and intestinal fatty-acid binding protein are elevated in serum in patients with acute ischemic stroke. Acta Neurol. Belg. 121:87–93. doi: 10.1007/s13760-018-0940-x - DOI - PubMed