The role of superoxide dismutase SOD-1 in microbe-gut-brain interaction

Gut microbes play an important role in regulating host physiology and metabolism. Recent
studies indicate that gut microbes affect memory formation and neurodegenerative disease
manifestation.
However, it is not fully understood how gut microbes influence gut–brain
communication. The nematode C. elegans has a relatively simple nervous system and will
readily ingest microbes from a petri dish. Therefore, C. elegans is a well-established model
organism for studying the neural basis of behaviors and host–microbe interactions. By
combining the two areas of research, we recently discovered that superoxide dismutase-1
(SOD-1), an enzyme that converts superoxide to less harmful peroxide, acts as a reactive
sensor of reactive oxygen species in the nervous system and regulates the behavioral response
to microbes. Our data indicate a previously unknown function of SOD-1 and suggest a potential
role for SOD-1 in regulating microbe-induced gut–brain communication.
In aim 1, we will determine how bacteria activate SOD-1. In aim 2, we will determine whether a neuropeptide
functions as a signaling molecule between the gut and the nervous system to modulate the
SOD-1 dependent response. In aim 3, we will define how SOD-1 and glutamatergic signaling
regulate behavioral response to microbes. The proposed work will advance our knowledge in
several ways. Our genetic model will open up a new research area for understanding the
microbe-induced communication at the gut–brain axis. In addition, the proposed experiments
will unveil new regulatory pathways of SOD-1. Our results may help to elucidate the underlying
mechanisms of gut dysbiosis among elderly adults and patients with neurodegenerative
diseases and may lead to the identification of potential therapeutic target.

Grant Number: 5R01GM131156-06
NIH Institute/Center: NIH
Principal Investigator: Howard Chang