Gut Microbes Regulate Innate Immunity and Epilepsy

Abstract

Epilepsy is a common chronic brain disease. There are many clinical methods to control epileptic seizures, such as anti-seizure medications (ASMs) or surgical removal of epileptogenic lesions. However, the pathophysiology of epilepsy is still unknown, making it difficult to control or prevent it. The host's immune system monitors gut microbes, interacts with microbes through pattern recognition receptors such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs) expressed by innate immune cells, and activates immune responses in the body to kill pathogens and balance the relationship between microbes and host. In addition, inflammatory responses induced by the innate immune system are seen in animal models of epilepsy and temporal lobe epilepsy brain tissue to combat pathogens or injuries. This review summarizes the potential relationship between gut microbes, innate immunity, and epilepsy based on recent research to provide more hints for researchers to explore this field further.

Keywords: central nervous system; epilepsy; gut–brain axis; innate immunity; microorganisms.

FIGURE 1

Gut–brain communication. Gut microbial surface substances and their metabolites can positively or negatively affect the CNS through the peripheral circulation or enteric nervous system, and microbial-derived neurotransmitters have regulatory effects on neurons or nerve cells after entering the brain. The metabolites can not only play an anti-inflammatory effect, protect the BBB but also play a pro-inflammatory effect, activate microglia to secrete inflammatory mediators, and then damage the BBB, leading to leakage.

FIGURE 2

Innate immune regulation within the CNS. LPS, albumin, and SCFAs in the peripheral circulation can act on various receptors, resulting in increased calcium conductance, down-regulated potassium channels, promotion of intracellular transcription, and release of immune molecules to cause BBB damage, which in turn lowers the seizure threshold or promotes epileptiform discharges, which eventually lead to seizures.