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Background <p>Methamphetamine (MA) abuse is a global public problem and methamphetamine addiction lacks of effective treatment. The gut microbes, involved in the gut-brain axis, remotely regulate methamphetamine addiction.</p> Results <p>In this study, we identified that <i>Lactobacillus johnsonii</i> (<i>L. johnsonii</i>) is involved in the metabolism of tyrosine. MA addiction disrupts the balance of gut microbes, reducing the abundance of <i>L. johnsonii</i>, destroying intestinal barrier integrity, and increasing the tyrosine level. The outbreak of tyrosine promotes a greater craving for MA in mice since it transfers from the intestine to VTA and NAc to promote microglia immune reactivity, which reduces energy supply to neurons and decreases presynaptic mitochondria in dopaminergic neurons. As a consequence, the dopaminergic presynaptic membrane reuptake process based on vesicular transport is affected, leading to maintain of dopamine in the synaptic cleft acting on the postsynaptic membrane with synaptic plasticity changes, resulting in MA craving. <i>L. johnsonii</i> transplantation rescues mice from MA craving by promoting the metabolism of tyrosine in intestine and improves the neuronal function in NAc and VTA.</p> Conclusions <p>Our results reveal that MA addiction disrupts gut microbiota homeostasis and promotes tyrosine-mediated dopamine system dysfunction. <i>L. johnsonii</i> transplantation is recommended for the treatment of methamphetamine craving.</p> Graphical Abstract <p></p> <p><MediaObject ID="MOESM15"> <VideoObject FileRef="MediaObjects/40168_2025_2197_MOESM15_ESM.mp4" VideoID="Dvp2A6yYRVvkdgcfzRZMhY"> <Caption Language="En" xml:lang="en"> <CaptionContent> <p>Video Abstract</p> </CaptionContent> </Caption> </VideoObject> </MediaObject></p>

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L. johnsonii alleviates methamphetamine craving via the metabolism of tyrosine

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月2日

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  • Ran Zhang,
  • Zhihao Cheng,
  • Dongsheng Liu,
  • Qin Shao,
  • Wei Sheng,
  • Hui Xu,
  • Peng Xu,
  • Youmei Wang,
  • Jiye Aa,
  • Guangji Wang,
  • Yuan Xie

摘要

Background

Methamphetamine (MA) abuse is a global public problem and methamphetamine addiction lacks of effective treatment. The gut microbes, involved in the gut-brain axis, remotely regulate methamphetamine addiction.

Results

In this study, we identified that Lactobacillus johnsonii (L. johnsonii) is involved in the metabolism of tyrosine. MA addiction disrupts the balance of gut microbes, reducing the abundance of L. johnsonii, destroying intestinal barrier integrity, and increasing the tyrosine level. The outbreak of tyrosine promotes a greater craving for MA in mice since it transfers from the intestine to VTA and NAc to promote microglia immune reactivity, which reduces energy supply to neurons and decreases presynaptic mitochondria in dopaminergic neurons. As a consequence, the dopaminergic presynaptic membrane reuptake process based on vesicular transport is affected, leading to maintain of dopamine in the synaptic cleft acting on the postsynaptic membrane with synaptic plasticity changes, resulting in MA craving. L. johnsonii transplantation rescues mice from MA craving by promoting the metabolism of tyrosine in intestine and improves the neuronal function in NAc and VTA.

Conclusions

Our results reveal that MA addiction disrupts gut microbiota homeostasis and promotes tyrosine-mediated dopamine system dysfunction. L. johnsonii transplantation is recommended for the treatment of methamphetamine craving.

Graphical Abstract

Video Abstract