U.S. flag

An official website of the United States government, Department of Justice.

Identification of Clostridium perfringens enterotoxin as a novel candidate trigger for Sudden Infant Death Syndrome

Award Information

Award #
2016-DN-BX-0176
Funding Category
Competitive
Location
Congressional District
Status
Past Project Period End Date
Funding First Awarded
2016
Total funding (to date)
$546,721

Description of original award (Fiscal Year 2016, $546,721)

As submitted by the proposer: Sudden Infant Death Syndrome (SIDS) is the leading cause of death in children between one month and one year of age. Surely, the impact of SIDS on parents and families is tragic. However, the exact cause of this disease remains unknown. Our current understanding of SIDS involves unexplained abnormalities in the region of the brain that controls our automatic desire to breathe. In SIDS, the neurons of this brain region are diminished in number. Furthermore, there is evidence of inflammation, suggesting that some form of damage has previously occurred. Typically, SIDS victims are laid down to sleep for the night and find themselves in sleeping positions that obstruct the airway (e.g. face down). Without this automatic respiratory drive, these infants fail to reposition themselves such that they can breathe adequately. They ultimately die from suffocation. The leading hypothesis for how SIDS related brain damage occurs is that there is a defect during brain development; however, we suggest that other mechanisms may be play. Bacterial toxins have also drawn attention in SIDS research. One toxin in particular, Clostridium perfringens enterotoxin, has been previously implicated. Interestingly, researchers have found that C. perfringens bacteria can be identified in the intestinal tracts of 81% of SIDS victims compared to just 20% of healthy infants. Furthermore, damage to the intestinal wall has been identified in 84% of SIDS cases and can be recreated in an animal model by exposing rodent intestinal tissue to enterotoxin. Comparison of high magnification images reveals striking similarities between the intestinal damage present in SIDS victims and the intestinal damage found in experimental animals. How enterotoxin may cause the lack of respiratory drive present in SIDS victims currently remains unknown. Preliminary data from our laboratory has identified that neurons comprising the brains respiratory center express claudin-3, a receptor for enterotoxin; hence these neurons will be damaged by enterotoxin if exposed. This novel finding provides mechanism for how enterotoxin may cause the brain damage found in SIDS. In light of this, we wish to collect brain and serum samples from SIDS victims to probe for enterotoxin. Additionally, we wish to collect intestinal contents and perform bacterial culture for C. perfringens, similar to what has been performed in previous studies. We will improve these bacterial culture studies by probing for C. perfringens carriage of the enterotoxin gene. Finally, we wish to characterize the SIDS gut microbiome and compare to that of controls. Note: This project contains a research and/or development component, as defined in applicable law. ca/ncf
Date Created: September 16, 2016