2. Academic Validation
  3. Pro-inflammatory Polarization of Macrophages Causes Intestinal Inflammation in Low-Birth-Weight Piglets and Mice

Pro-inflammatory Polarization of Macrophages Causes Intestinal Inflammation in Low-Birth-Weight Piglets and Mice

  • J Nutr. 2023 Apr 19;S0022-3166(23)37559-X. doi: 10.1016/j.tjnut.2023.04.016.
Xiangyu Zhang 1,  Yujun Wu 1,  Xiaoyi Liu 1,  Xu Lin 1,  Yisi Liu 1,  Luyuan Kang 1,  Hao Ye 2,  Zhenyu Wang 1,  Yingying Ma 1,  Zhaolai Dai 1,  Dongsheng Che 3,  Yu Pi 1,  Lianqiang Che 4,  Junjun Wang 1,  Dandan Han 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
  • 2 Department of Animal Sciences, Wageningen University, Wageningen 6700 AH, Netherlands.
  • 3 College of Animal Science and Technology, Jilin Agricultural University, Jilin, 130118, China.
  • 4 Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Institute of Animal Nutrition, Sichuan Agricultural University, Sichuan 611130, China.
  • 5 State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China. Electronic address: handandan@cau.edu.cn.
PMID: 37084872 DOI: 10.1016/j.tjnut.2023.04.016
Abstract

Background: Low-birth-weight (LBW) Animals suffer from intestinal damage and inflammation in their early life.

Objectives: The aim of this study was to investigate the role of macrophages in intestinal inflammation in LBW piglets and mice.

Methods: Major genes involved in intestinal barrier function such as claudin-1, zonula occludens-1 (ZO-1), occludin, and Mucin 2 and inflammatory cytokines such as IL-1β, TNF-α, IL-10, and IL-13 were evaluated in 21-day-old, normal birth weight (NBW) and LBW piglets and mice. Macrophage markers such as CD16/32, CD163, and CD206 were also assessed by immunofluorescence and flow cytometry. Polarized and unpolarized macrophages were further transferred into NBW and LBW mice, followed by evaluation of intestinal permeability and inflammation.

Results: Claudin-1 mRNA in LBW piglets as well as claudin-1, occludin, ZO-1 and Mucin 2 mRNAs in LBW mice was significantly downregulated. IL-1β and TNF-α were significantly upregulated in LBW piglets (P < 0.05). LBW mice showed a reduced expression of IL-10 and IL-13 (P < 0.05), with a heightened IL-6 level (P < 0.01) in the jejunum. CD16, a marker for M1 macrophages, was significantly elevated in the jejunum of LBW piglets, whereas CD163, a marker for M2 macrophages, was significantly decreased (P < 0.05). Similarly, LBW mice had more CD11b+CD16/32+ M1 macrophages (P < 0.05) and fewer CD206+ M2 macrophages (P < 0.01) than NBW mice. Moreover, transfer of M1 macrophages exacerbated intestinal inflammation in LBW mice. Furthermore, two major glycolysis-associated genes, Hexokinase 2 (HK2) and Lactate Dehydrogenase A (LDHA), were significantly upregulated in LBW piglets and mice (P < 0.05).

Conclusions: This study revealed for the first time that the intestinal macrophages are polarized towards a pro-inflammatory phenotype in LBW piglets and mice, contributing to intestinal inflammation. The findings of this study provide new options for the management of intestinal inflammation in LBW Animals.

Keywords

glycolysis; intestinal barrier; intestinal inflammation; low-birth-weight; macrophage.

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