Background <p>Wild isolates of <i>Toxoplasma gondii</i> may exhibit different virulence characteristics and host adaptability compared with those of laboratory strains. In this study, we isolated a novel rodent-derived <i>T. gondii</i> strain, denoted TgRodGz1, and evaluated its pathogenic features. </p> Methods <p>TgRodGz1 was isolated from T. gondii-positive wild rodents in Guangdong Province and compared with the RH and Me49 strains in C57BL/6 mice. Virulence and intestinal injury were evaluated by survival analysis, brain cyst quantification, histopathology, tight junction assessment and qPCR. Gut microbiota and metabolic alterations were analyzed by metagenomic sequencing and LC–MS/MS-based metabolomics.</p> Results <p>Compared with the<i>T. gondii</i> laboratory strains RH and Me49, TgRodGz1 was associated with more pronounced intestinal injury, including villus atrophy, barrier disruption and downregulation of tight junction proteins and increased gut permeability and inflammation. Metagenomic analysis revealed significant intestinal flora dysbiosis, with a marked reduction in beneficial bacteria and expansion of pathogenic bacteria. Metabolomic analysis revealed suppression of arachidonic acid (ARA) metabolism during TgRodGz1 infection. Supplementation with ARA did not directly inhibit parasite growth but significantly alleviated intestinal lesions, reduced brain cyst burden and attenuated inflammatory responses, including microglial activation.</p> Conclusions <p> These findings suggest that TgRodGz1 represents a distinct <i>T. gondii</i> genotype associated with pronounced intestinal pathology and suggest that ARA supplementation may alleviate intestinal and neuroinflammatory changes associated with <i>T. gondii</i> infection.</p> Graphical Abstract <p></p>

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The gut metabolite arachidonic acid alleviates intestinal injury induced by a Toxoplasma gondii strain isolated from a wild rodent

  • Hao Yuan,
  • Yining Song,
  • Linchong Nie,
  • Zipeng Yang,
  • Liulu Yang,
  • Kunmei Yang,
  • Yurong Yang,
  • Wenhao Li,
  • Xianghe Wang,
  • Xiu-Xiang Zhang,
  • Yan Hua,
  • Zi-Guo Yuan

摘要

Background

Wild isolates of Toxoplasma gondii may exhibit different virulence characteristics and host adaptability compared with those of laboratory strains. In this study, we isolated a novel rodent-derived T. gondii strain, denoted TgRodGz1, and evaluated its pathogenic features.

Methods

TgRodGz1 was isolated from T. gondii-positive wild rodents in Guangdong Province and compared with the RH and Me49 strains in C57BL/6 mice. Virulence and intestinal injury were evaluated by survival analysis, brain cyst quantification, histopathology, tight junction assessment and qPCR. Gut microbiota and metabolic alterations were analyzed by metagenomic sequencing and LC–MS/MS-based metabolomics.

Results

Compared with theT. gondii laboratory strains RH and Me49, TgRodGz1 was associated with more pronounced intestinal injury, including villus atrophy, barrier disruption and downregulation of tight junction proteins and increased gut permeability and inflammation. Metagenomic analysis revealed significant intestinal flora dysbiosis, with a marked reduction in beneficial bacteria and expansion of pathogenic bacteria. Metabolomic analysis revealed suppression of arachidonic acid (ARA) metabolism during TgRodGz1 infection. Supplementation with ARA did not directly inhibit parasite growth but significantly alleviated intestinal lesions, reduced brain cyst burden and attenuated inflammatory responses, including microglial activation.

Conclusions

These findings suggest that TgRodGz1 represents a distinct T. gondii genotype associated with pronounced intestinal pathology and suggest that ARA supplementation may alleviate intestinal and neuroinflammatory changes associated with T. gondii infection.

Graphical Abstract