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Lactiplantibacillus plantarum ZJ316 inhibits Helicobacter pylori-induced inflammation by regulating the p38 MAPK signaling pathway
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Shiying WU*, Mingyang HU, Yi XU, Luying XIE, Yuenuo LUO, Jiayi FAN, Qing GU*
Acta Microbiologica Sinica | 2025, 65(12) : 5362 - 5379
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Acta Microbiologica Sinica | 2025, 65(12): 5362-5379
Research Article
Lactiplantibacillus plantarum ZJ316 inhibits Helicobacter pylori-induced inflammation by regulating the p38 MAPK signaling pathway
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Shiying WU*, Mingyang HU, Yi XU, Luying XIE, Yuenuo LUO, Jiayi FAN, Qing GU*
Affiliations
  • Zhejiang Key Laboratory of Food Microbiology and Nutritional Health, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
Published: 2025-12-04 doi: 10.13343/j.cnki.wsxb.20250368
Outline
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Helicobacter pylori infection is a major causative factor for chronic gastritis and gastric cancer, while current antibiotic therapies are facing increasingly severe resistance. Probiotics have emerged as a promising approach for anti-H. pylori research due to their high safety. Notably, certain Lactobacillus strains have been demonstrated to effectively alleviate H. pylori-induced inflammatory responses, yet their underlying molecular regulatory mechanisms remain unclear. Objective To investigate the molecular mechanism by which Lactiplantibacillus plantarum ZJ316 inhibits the H. pylori-induced inflammatory response by modulating the p38 mitogen-activated protein kinase (MAPK) signaling pathway in the host cells and assess the regulatory effect of this strain on gastric microecological homeostasis, thus providing a theoretical basis for the development of probiotic therapeutics targeting H. pylori. Methods We integrated cell experiments (human gastric adenocarcinoma cell line AGS) and animal experiments (C57BL/6 mice) and employed Western blotting (to determine the phosphorylation level of p38 MAPK), transcriptome sequencing and RT-qPCR (to analyze differential gene expression), ELISA [to determine the levels of inflammatory cytokines interleukin (IL)-8 and IL-10], 16S rRNA gene sequencing (to unveil the gastric flora structure), and hematoxylin-eosin staining (to observe gastric mucosal damage) to systematically study the intervention effect of L. plantarum ZJ316 on H. pylori infection. Results At the cellular level, L. plantarum ZJ316 inhibited H. pylori-induced p38 MAPK phosphorylation, with the inhibition rates of 21.95% and 33.72% at the time points of 1 h and 2 h, respectively (P<0.01). It down-regulated the expression of pathway genes such as MAP3K8 and FOS, and lowered the mRNA levels of the pro-inflammatory cytokines interferon-γ, tumor necrosis factor-α, and IL-6 by 43.26%, 35.95%, and 51.91%, respectively (P<0.01). The combination of this strain with adezmapimod, a p38 MAPK-specific inhibitor, further enhanced the inhibitory effect. In animal experiments, L. plantarum ZJ316 significantly attenuated gastric mucosal pathological injury and inflammatory response, and 16S rRNA gene sequencing revealed that ZJ316 reduced the relative abundance of pathogenic Pseudomonadota and significantly increased the relative abundance of Bacillota [(54.8±9.9)% vs. (27.8±5.9)%, P<0.01] in the stomach. When ZJ316 was combined with adezmapimod, the relative abundance of Bacteroidota was elevated [(58.5±5.2)% vs. (47.8±6.9)%, P<0.05], and specific beneficial genera such as Alistipes were synergistically enriched (an increase of 69.52% compared with the H. pylori group). Conclusion L. plantarum ZJ316 alleviated the inflammatory response triggered by H. pylori infection by inhibiting the p38 MAPK pathway and remodeled the gastric microecological structure. The findings provide a theoretical basis for the inhibition of H. pylori-induced inflammation by lactobacilli and the development of probiotic-based functional foods.

Lactiplantibacillus plantarum ZJ316  /  Helicobacter pylori  /  p38 MAPK  /  inflammatory response
Shiying WU, Mingyang HU, Yi XU, Luying XIE, Yuenuo LUO, Jiayi FAN, Qing GU. Lactiplantibacillus plantarum ZJ316 inhibits Helicobacter pylori-induced inflammation by regulating the p38 MAPK signaling pathway[J]. Acta Microbiologica Sinica, 2025 , 65 (12) : 5362 -5379 . DOI: 10.13343/j.cnki.wsxb.20250368
  • National Natural Science Foundation of China(32001667)
  • Zhejiang Gongshang University Provincial Colleges and Universities Basic Research Operating Expenses Program(QRK23006)
Year 2025 volume 65 Issue 12
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Article Info
doi: 10.13343/j.cnki.wsxb.20250368
  • Receive Date:2025-05-06
  • Online Date:2025-12-08
  • Published:2025-12-04
Article Data
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History
  • Received:2025-05-06
  • Accepted:2025-06-19
Funding
National Natural Science Foundation of China(32001667)
Zhejiang Gongshang University Provincial Colleges and Universities Basic Research Operating Expenses Program(QRK23006)
Affiliations
    Zhejiang Key Laboratory of Food Microbiology and Nutritional Health, Zhejiang Gongshang University, Hangzhou, Zhejiang, China

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*E-mail: GU Qing, ;
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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