State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing, 100193, China.
Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, 100193, China.
Amino Acids. 2022 Mar;54(3):353-364. doi: 10.1007/s00726-021-03011-w. Epub 2021 Jun 4.
Intestinal dysfunction is commonly observed in humans and animals. Glycine (Gly) is a functional amino acid with anti-inflammatory and anti-apoptotic properties. The objective of this study was to test the protective effects of Gly against lipopolysaccharide (LPS)-induced intestinal injury. 28 C57BL/6 mice with a body weight (BW) of 18 ± 2 g were randomly assigned into four groups: CON (control), GLY (orally administered Gly, 5 g/kg BW/day for 6 days), LPS (5 mg/kg BW on day 7, i. p.), and GLY + LPS (Gly pretreatment and LPS administration). Histological alterations, inflammatory responses, epithelial cell apoptosis, and changes of the intestinal microbiota were analyzed. Results showed that, compared with the CON group, mice in the LPS treatment group showed decreased villus height, increased crypt depth, and decreased ratio of villus height to crypt depth, which were significantly attenuated by Gly. Neither LPS nor Gly treatment altered morphology of the distal colon tissues. LPS increased the apoptosis of jejunum and colon epithelial cells and protein abundance of cleaved caspase3 in the jejunum, which were markedly abrogated by Gly. LPS also elevated the mRNA levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MYD88), pro-inflammatory cytokines, and chemokines in the jejunum and colon. These alterations were significantly suppressed by Gly. In addition, Gly supplementation attenuated infiltration of CD4, CD8 T-lymphocytes, CD11b and F4/80 macrophages in the colon. Furthermore, Gly increased the relative abundance of Mucispirillum, Lachnospiraceae-NK4A136-group, Anaerotruncus, Faecalibaculum, Ruminococcaceae-UCG-014, and decreased the abundance of Bacteroides at genus level. Supplementation with Gly might be a nutritional strategy to ameliorate LPS-induced intestinal injury in mice.
肠道功能障碍在人和动物中很常见。甘氨酸（Gly）是一种具有抗炎和抗凋亡作用的功能性氨基酸。本研究旨在测试甘氨酸（Gly）对脂多糖（LPS）诱导的肠道损伤的保护作用。28 只体重（BW）为 18±2 g 的 C57BL/6 小鼠被随机分为四组：CON（对照组）、GLY（口服甘氨酸，5 g/kg BW/天，连续 6 天）、LPS（第 7 天 5 mg/kg BW，腹腔注射）和 GLY+LPS（甘氨酸预处理和 LPS 给药）。分析了组织学改变、炎症反应、上皮细胞凋亡和肠道微生物群的变化。结果表明，与 CON 组相比，LPS 处理组小鼠的绒毛高度降低，隐窝深度增加，绒毛高度与隐窝深度的比值降低，这些变化均被甘氨酸显著改善。LPS 或甘氨酸处理均未改变远端结肠组织的形态。LPS 增加了空肠和结肠上皮细胞的凋亡以及空肠中 cleaved caspase3 的蛋白丰度，这些变化均被甘氨酸明显阻断。LPS 还增加了空肠和结肠中 Toll 样受体 4（TLR4）、髓样分化因子 88（MYD88）、促炎细胞因子和趋化因子的 mRNA 水平。这些变化均被甘氨酸显著抑制。此外，甘氨酸补充剂减轻了结肠中 CD4、CD8 T 淋巴细胞、CD11b 和 F4/80 巨噬细胞的浸润。此外，甘氨酸增加了 Mucispirillum、Lachnospiraceae-NK4A136 组、Anaerotruncus、Faecalibaculum、Ruminococcaceae-UCG-014 的相对丰度，降低了属水平的 Bacteroides 的丰度。甘氨酸的补充可能是一种改善 LPS 诱导的小鼠肠道损伤的营养策略。
