Abstract
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.
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Abbreviations
- CCL:
-
Chemokine (C–C motif) ligand
- CON:
-
Control group
- Gly:
-
Glycine
- GLY + LPS:
-
Glycine plus LPS co-treatment group
- H&E:
-
Hematoxylin and eosin
- IECs:
-
Intestinal epithelial cells
- IFN-γ:
-
Interferon-γ
- IL-1β:
-
Interleukin-1β
- LPS:
-
Lipopolysaccharide
- MYD88:
-
Myeloid differentiation factor 88
- NF-κB:
-
Nuclear factor κB
- OTU:
-
Operational taxonomic unit
- PCA:
-
Principal component analysis
- qRT-PCR:
-
Quantitative real-time PCR
- TLR4:
-
Toll-like receptor 4
- TNF-α:
-
Tumor necrosis factor-α
- TUNEL:
-
Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling
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This work was supported by the National Natural Science Foundation of China (Nos. 31625025, 31572410, and 31272451).
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YZ and ZW: designed the study, performed the laboratory work, and drafted the manuscript; TM: conducted the 16S rDNA sequencing and data analyses; HJ: provided methodology; YY: analyzed the data; ZW had primary responsibility for final content. All authors read and approved the final manuscript.
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This animal study was approved by the Animal Use and Care Committee of China Agricultural University.
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Zhang, Y., Mu, T., Jia, H. et al. Protective effects of glycine against lipopolysaccharide-induced intestinal apoptosis and inflammation. Amino Acids 54, 353–364 (2022). https://doi.org/10.1007/s00726-021-03011-w
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DOI: https://doi.org/10.1007/s00726-021-03011-w