The proper communication between gut and brain is pivotal for the maintenance of health and, dysregulation of the gut-brain axis can lead to several clinical disorders. In Parkinson’s disease (PD) 85% of all patients experienced constipation many years before showing any signs of motor phenotypes. For differential diagnosis and preventive treatment, there is an urgent need for the identification of biomarkers indicating early disease stages long before the disease phenotype manifests. DJ-1 is a chaperone protein involved in the protection against PD and genetic mutations in this protein have been shown to cause familial PD. However, how the deficiency of DJ-1 influences the risk of PD remains incompletely understood. In the present study, we provide evidence that DJ-1 is implicated in shaping the gut microbiome including; their metabolite production, inflammation and innate immune cells (ILCs) development. We revealed that deficiency of DJ-1 leads to a significant increase in two specific genera/species, namely Alistipes and Rikenella. In DJ-1 knock-out (DJ-1^-/-) mice the production of fecal calprotectin and MCP-1 inflammatory proteins were elevated. Fecal and serum metabolic profile showed that malonate which influences the immune system was significantly more abundant in DJ-1^−/− mice. DJ-1 appeared also to be involved in ILCs development. Further, inflammatory genes related to PD were augmented in the midbrain of DJ-1^−/− mice. Our data suggest that metabolites and inflammation produced in the gut could be used as biomarkers for PD detection. Perhaps, these metabolites and inflammatory mediators could be involved in triggering inflammation resulting in PD pathology.

肠道和大脑之间的适当沟通对于维持健康至关重要，而肠道-大脑轴的失调会导致几种临床疾病。在帕金森病 (PD) 中，85% 的所有患者在表现出任何运动表型迹象之前多年就经历了便秘。对于鉴别诊断和预防性治疗，迫切需要在疾病表型出现之前很久就识别出表明疾病早期阶段的生物标志物。DJ-1 是一种参与 PD 保护的伴侣蛋白，该蛋白的基因突变已被证明会导致家族性 PD。然而，DJ-1 的缺乏如何影响 PD 的风险仍然不完全清楚。在本研究中，我们提供的证据表明 DJ-1 与塑造肠道微生物群有关，包括：它们的代谢产物产生、炎症和先天免疫细胞 (ILC) 的发育。我们揭示了 DJ-1 的缺乏导致两个特定属/种的显着增加，即Alistipes和Rikenella。在 DJ-1 敲除 (DJ-1 ^-/- ) 小鼠中，粪便钙卫蛋白和 MCP-1 炎症蛋白的产生升高。粪便和血清代谢谱显示影响免疫系统的丙二酸在 DJ-1 ^-/-小鼠中明显更丰富。DJ-1 似乎也参与了 ILC 的开发。此外，与 PD 相关的炎症基因在 DJ-1 ^-/-小鼠的中脑中增加。我们的数据表明，肠道中产生的代谢物和炎症可用作 PD 检测的生物标志物。也许，这些代谢物和炎症介质可能参与引发炎症，导致 PD 病理。