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Published on: February 3, 2016
Gut microbiota from essential tremor patients aggravates tremors in mice
Ruo-Xin Zhang1, Jia-Ting Xu1, Hao-Jie Zhong1
1Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota-Targeted Therapies of Guangdong Province, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
Background And Objective:
Essential tremor (ET) lacks effective treatments because its underlying mechanism is largely unknown, but may involve gut microbiota via the microbiome-gut-brain axis. We explored the effects of gut microbiota on ET in mice.
Methods:
Specific pathogen-free C57BL/6J mice were gavaged with stools from ET patients or matched healthy individuals. After 3 weeks of gavaging, behavioral tests were performed on all mice. Next, each mouse was injected with harmaline to induce tremors. The tremor duration was recorded; the tremor score was estimated every 30 min. Behavioral tests were repeated after modeling. Intestinal tissues and fecal samples of the mice were examined using histology and 16Sr DNA sequencing, respectively.
Results:
Compared with mice receiving microbiota from healthy controls, mice receiving fecal suspensions from ET patients showed worse performance in the pre-modeling behavioral tests. After modeling, ET-group mice showed significantly greater tremor scores, longer tremor duration, and worse motor performance. They also had significantly lower body weight and lower fecal pellet count. Pathological scoring revealed more severe intestinal lesions in ET-group mice. The 16S rDNA sequencing data revealed significant differences in microbiota indices, and a correlation between these indices and tremors in mice. Functional predictions indicated that the abundance of GABA-related enzymes was altered in ET-group mice.
Conclusion:
Mice transplanted with gut microbiota from ET patients showed worse performance in behavioral tests. After modeling, ET-group mice presented longer tremor duration, higher tremor score, and worse motor performance. This study provides evidence for gut microbiota dysbiosis that may affect the pathogenesis of ET.
Insights
Gut microbiota from essential tremor (ET) patients worsened tremor symptoms and motor performance in mice. This suggests gut dysbiosis may play a role in essential tremor pathogenesis.
Area of Science:
- Neuroscience
- Microbiology
- Gastroenterology
Background:
- Essential tremor (ET) is a neurological disorder with unknown mechanisms and limited treatment options.
- The gut-brain axis and microbiome-gut-brain axis are increasingly recognized as potential modulators of neurological conditions.
- This study investigates the role of gut microbiota in the pathogenesis of essential tremor.
Purpose of the Study:
- To explore the effects of gut microbiota transplantation from essential tremor patients on ET-like symptoms in mice.
- To assess behavioral and motor performance changes in mice receiving ET patient-derived microbiota.
- To analyze the gut microbial composition and intestinal pathology in response to ET microbiota.
Main Methods:
- Fecal microbiota transplantation from ET patients and healthy controls into C57BL/6J mice.
- Behavioral tests and tremor modeling using harmaline injection.
- Assessment of tremor duration, tremor score, motor performance, body weight, and fecal output.
- Histological examination of intestinal tissues and 16S rDNA sequencing of fecal samples.
Main Results:
- Mice receiving ET patient microbiota exhibited poorer pre-modeling behavioral test performance.
- Post-modeling, ET-group mice showed significantly increased tremor scores, longer tremor duration, and impaired motor function.
- ET-group mice had reduced body weight, lower fecal pellet counts, more severe intestinal lesions, and altered gut microbiota composition, including changes in GABA-related enzymes.
Conclusions:
- Gut microbiota transplantation from ET patients induces and exacerbates ET-like symptoms in mice.
- Significant alterations in gut microbiota composition and function are associated with ET pathogenesis.
- This study provides evidence supporting gut dysbiosis as a contributing factor to essential tremor.
