An Epilepsy Ireland part-funded study investigating how the bacteria in the gut affect people with autoimmune encephalitis has been published in the renowned medical journal, Epilepsia. The study was led by Prof. Gianpiero Cavalleri of the Royal College of Surgeons Ireland and funding for the study was provided by Epilepsy Ireland via the Health Research Board/Health Research Charities Ireland Joint Funding scheme (HRB/HRCI JFS).
The study also involved international collaboration, with researchers and research institutions from the US, UK and Italy also involved.
Autoimmune encephalitis (AE) is a rare cause of epilepsy. In AE, the body’s immune system mistakenly targets healthy brain tissue, responding as though it were fighting off a virus or bacteria. It does this by generating a large number of proteins known as antibodies, which then begin to attack the brain’s healthy cells.
LGI1‐antibody encephalitis (LGI1‐Ab‐E) is a specific type of AE in which the immune system makes antibodies against the LGI1 protein on brain cells. These antibodies attacking this protein can cause epilepsy, as well as several other challenging symptoms, in patients living with AE.
Previous research has shown that more than 90% of patients with LGI1 antibodies have a specific immune-related gene variant, called HLA-DRB1*07:01. This genetic variant increases the risk of AE, but it is also found in around 12% of the rest of the world’s healthy population.
This means that other triggers - possibly environmental - may be involved in a person developing AE. The gut microbiome (the trillions of bacteria in our digestive system) is a strong candidate because it can influence immunity and brain health.
Therefore, as part of their research, the study aimed to find out whether people with LGI1‐Ab‐E have a different gut microbiome compared to closely matched healthy people, and whether those differences might link to the known genetic risk factor (HLA‐DRB1*07:01).
As part of their investigations, the researchers recruited 42 people with LGI1‐Ab‐E and 27 healthy controls (often spouses or close relatives as they would have a similar environment/diet) from Ireland and the UK.
They collected stool and saliva samples for gut microbiome analysis using advanced DNA sequencing and they then compared the bacterial composition and the predicted functional capacity of the microbiome between patients with LGI1‐Ab‐E and healthy controls.
This yielded the following key findings:
- Although no individual bacterial species was significantly more or less common in patients after statistical analysis, there was a trend towards patients having more bacteria in the mouth and small intestine.
- Researchers found that people with LGI1-Ab-E had a different gut bacteria balance compared to healthy individuals. Specifically, they had fewer Firmicutes and more Bacteroidetes. This shift was more pronounced in those carrying more copies of the HLA-DRB1*07:01 gene variant, suggesting a possible link between genetics, gut microbiome changes, and immune-related dysfunction.
- Researchers looked at biological pathways in the gut and found some clear differences between people with AE and healthy individuals. In healthy controls, certain gut functions were more active, especially those involved in making coenzyme A (which helps with energy production and metabolism) and those involved in producing short-chain fatty acids (SCFAs), which are important for gut health and reducing inflammation.
As a result of their findings, the researchers have concluded that LGI1‐Ab‐E is associated with subtle but consistent changes in the gut microbiome which might contribute to brain‐targeting autoimmune reactions and inflammation. This could explain why only some HLA‐DRB1*07:01 carriers get the disease.
However, the researchers have acknowledged that larger studies are needed to confirm and expand on these findings.
The publication of this Epilepsy Ireland supported research is timely as we have recently launched our 9th Research Funding Call under the HRB/HRCI JFS. This research which has been published in the leading medical journal, Epilepsia, shows the impact of our research investments and how it can help fund vital research and help provide future research pathways for those investigating AE.
In addition, at our National Conference, we will be joined by the lead author of the paper Dr. Edmund Gilbert from the RCSI, who will discuss this research in more detail as well as the role of the microbiome in epilepsy. If you’d like to join us and hear more about this research and from other incredible speakers, visit the ‘Epilepsy Ireland National Conference 2025’ page on our website.
We would like to congratulate all the researchers involved in this important study - particularly Professor Gianpiero Cavalleri and all the researchers at the RCSI and FutureNeuro who were involved in this research. We would also like to take this opportunity to thank all our supporters who made this research possible. Without your continued efforts on our behalf, we would not be able to provide funding to research like this, and to be seeking to support new research investments under our 9th Research Funding Call.
You can read this study in full by visiting the Online Wiley website and if you or a loved one need any information or support on your journey with epilepsy, please do not hesitate to get in touch with your local Community Resource Officer. You can find their details by visiting the ‘Our Local Service’ page on our website.