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Lactobacillus rhamnosus GG Attenuates Lipopolysaccharide-Induced Inflammation and Barrier Dysfunction by Regulating MAPK/NF-κB Signaling and Modulating Metabolome in the Piglet Intestine.
J Nutr. 2020 05 01; 150(5):1313-1323.JN

Abstract

BACKGROUND

Probiotic Lactobacillius rhamnosus GG (LGG) shows beneficial immunomodulation on cultured cell lines in vitro and in mouse models.

OBJECTIVE

The aim was to investigate the effects of LGG on intestinal injury and the underlying mechanisms by elucidating inflammatory signaling pathways and metabolomic response to LPS stimulation in the piglet intestine.

METHODS

Piglets (Duroc × Landrace × Large White, including males and female; 8.6 ± 1.1 kg) aged 28 d were assigned to 3 groups (n = 6/group): oral inoculation with PBS for 2 wk before intraperitoneal injection of physiological saline [control (CON)] or LPS (25 μg/kg body weight; LPS) or oral inoculation with LGG for 2 wk before intraperitoneal injection of LPS (LGG+LPS). Piglets were killed 4 h after LPS injection. Systemic inflammation, intestinal integrity, inflammation signals, and metabolomic characteristics in the intestine were determined.

RESULTS

Compared with CON, LPS stimulation significantly decreased ileal zonula occludens 1 (ZO-1; 44%), claudin-3 (44%), and occludin (41%) expression; increased serum diamineoxidase (73%), D-xylose (19%), TNF-α (43%), and IL-6 (55%) concentrations; induced p38 mitogen-activated protein kinase (p38 MAPK; 85%), extracellular signal-regulated kinase (ERK; 96%), and NF-κB p65 phosphorylation (37%) (P < 0.05). Compared with LPS stimulation alone, LGG pretreatment significantly enhanced the intestinal barrier by upregulating expressions of tight junction proteins (ZO-1, 73%; claudin-3, 55%; occludin, 67%), thereby decreasing serum diamineoxidase (26%) and D-xylose (28%) concentrations, and also reduced serum TNF-α expression (16%) and ileal p38 MAPK (79%), ERK (43%) and NF-κB p65 (37%) phosphorylation levels (P < 0.05). Metabolomic analysis showed clear separation between each group. The concentrations of caprylic acid [fold-change (FC) = 2.39], 1-mono-olein (FC = 2.68), erythritol (FC = 4.62), and ethanolamine (FC = 4.47) significantly increased in the intestine of LGG + LPS piglets compared with the LPS group (P < 0.05).

CONCLUSIONS

These data suggest that LGG alleviates gut inflammation, improves intestinal barrier function, and modulates the metabolite profile of piglets challenged with LPS. This trial was registered at the Zhejiang University (http://www.lac.zju.edu.cn) as ZJU20170529.

Authors+Show Affiliations

College of Animal Science, Zhejiang University, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, China. Institute of Animal Nutrition, College of Animal Science and Technology, Zhejiang A&F University, Hangzhou, China.College of Animal Science, Zhejiang University, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, China. Institute of Animal Nutrition, College of Animal Science and Technology, Zhejiang A&F University, Hangzhou, China.College of Animal Science, Zhejiang University, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, China. Institute of Animal Nutrition, College of Animal Science and Technology, Zhejiang A&F University, Hangzhou, China.Institute of Animal Nutrition, College of Animal Science and Technology, Zhejiang A&F University, Hangzhou, China.Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA, USA.College of Animal Science, Zhejiang University, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, China.College of Animal Science, Zhejiang University, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, China.College of Animal Science, Zhejiang University, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, China.College of Animal Science, Zhejiang University, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, China. Institute of Animal Nutrition, College of Animal Science and Technology, Zhejiang A&F University, Hangzhou, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32027752

Citation

Mao, Jiangdi, et al. "Lactobacillus Rhamnosus GG Attenuates Lipopolysaccharide-Induced Inflammation and Barrier Dysfunction By Regulating MAPK/NF-κB Signaling and Modulating Metabolome in the Piglet Intestine." The Journal of Nutrition, vol. 150, no. 5, 2020, pp. 1313-1323.
Mao J, Qi S, Cui Y, et al. Lactobacillus rhamnosus GG Attenuates Lipopolysaccharide-Induced Inflammation and Barrier Dysfunction by Regulating MAPK/NF-κB Signaling and Modulating Metabolome in the Piglet Intestine. J Nutr. 2020;150(5):1313-1323.
Mao, J., Qi, S., Cui, Y., Dou, X., Luo, X. M., Liu, J., Zhu, T., Ma, Y., & Wang, H. (2020). Lactobacillus rhamnosus GG Attenuates Lipopolysaccharide-Induced Inflammation and Barrier Dysfunction by Regulating MAPK/NF-κB Signaling and Modulating Metabolome in the Piglet Intestine. The Journal of Nutrition, 150(5), 1313-1323. https://doi.org/10.1093/jn/nxaa009
Mao J, et al. Lactobacillus Rhamnosus GG Attenuates Lipopolysaccharide-Induced Inflammation and Barrier Dysfunction By Regulating MAPK/NF-κB Signaling and Modulating Metabolome in the Piglet Intestine. J Nutr. 2020 05 1;150(5):1313-1323. PubMed PMID: 32027752.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lactobacillus rhamnosus GG Attenuates Lipopolysaccharide-Induced Inflammation and Barrier Dysfunction by Regulating MAPK/NF-κB Signaling and Modulating Metabolome in the Piglet Intestine. AU - Mao,Jiangdi, AU - Qi,Siri, AU - Cui,Yanjun, AU - Dou,Xiaoxiao, AU - Luo,Xin M, AU - Liu,Jianxin, AU - Zhu,Tao, AU - Ma,Yanfei, AU - Wang,Haifeng, PY - 2019/08/27/received PY - 2019/09/16/revised PY - 2020/01/10/accepted PY - 2020/2/7/pubmed PY - 2020/9/15/medline PY - 2020/2/7/entrez KW - Lactobacillus rhamnosus GG KW - MAPK signaling KW - immunomodulation KW - intestine KW - metabolites KW - piglet model SP - 1313 EP - 1323 JF - The Journal of nutrition JO - J. Nutr. VL - 150 IS - 5 N2 - BACKGROUND: Probiotic Lactobacillius rhamnosus GG (LGG) shows beneficial immunomodulation on cultured cell lines in vitro and in mouse models. OBJECTIVE: The aim was to investigate the effects of LGG on intestinal injury and the underlying mechanisms by elucidating inflammatory signaling pathways and metabolomic response to LPS stimulation in the piglet intestine. METHODS: Piglets (Duroc × Landrace × Large White, including males and female; 8.6 ± 1.1 kg) aged 28 d were assigned to 3 groups (n = 6/group): oral inoculation with PBS for 2 wk before intraperitoneal injection of physiological saline [control (CON)] or LPS (25 μg/kg body weight; LPS) or oral inoculation with LGG for 2 wk before intraperitoneal injection of LPS (LGG+LPS). Piglets were killed 4 h after LPS injection. Systemic inflammation, intestinal integrity, inflammation signals, and metabolomic characteristics in the intestine were determined. RESULTS: Compared with CON, LPS stimulation significantly decreased ileal zonula occludens 1 (ZO-1; 44%), claudin-3 (44%), and occludin (41%) expression; increased serum diamineoxidase (73%), D-xylose (19%), TNF-α (43%), and IL-6 (55%) concentrations; induced p38 mitogen-activated protein kinase (p38 MAPK; 85%), extracellular signal-regulated kinase (ERK; 96%), and NF-κB p65 phosphorylation (37%) (P < 0.05). Compared with LPS stimulation alone, LGG pretreatment significantly enhanced the intestinal barrier by upregulating expressions of tight junction proteins (ZO-1, 73%; claudin-3, 55%; occludin, 67%), thereby decreasing serum diamineoxidase (26%) and D-xylose (28%) concentrations, and also reduced serum TNF-α expression (16%) and ileal p38 MAPK (79%), ERK (43%) and NF-κB p65 (37%) phosphorylation levels (P < 0.05). Metabolomic analysis showed clear separation between each group. The concentrations of caprylic acid [fold-change (FC) = 2.39], 1-mono-olein (FC = 2.68), erythritol (FC = 4.62), and ethanolamine (FC = 4.47) significantly increased in the intestine of LGG + LPS piglets compared with the LPS group (P < 0.05). CONCLUSIONS: These data suggest that LGG alleviates gut inflammation, improves intestinal barrier function, and modulates the metabolite profile of piglets challenged with LPS. This trial was registered at the Zhejiang University (http://www.lac.zju.edu.cn) as ZJU20170529. SN - 1541-6100 UR - https://www.unboundmedicine.com/medline/citation/32027752/Lactobacillus_rhamnosus_GG_Attenuates_Lipopolysaccharide_Induced_Inflammation_and_Barrier_Dysfunction_by_Regulating_MAPK/NF_κB_Signaling_and_Modulating_Metabolome_in_the_Piglet_Intestine_ L2 - https://academic.oup.com/jn/article-lookup/doi/10.1093/jn/nxaa009 DB - PRIME DP - Unbound Medicine ER -