Analyses of host-microbiota interactions in aging C. elegans hosts - Project Summary/Abstract
“Analyses of host-microbiota interactions in aging C. elegans hosts”
Gut microbiota – microorganisms and their genes – influence host physiology.
Microorganisms such as bacteria can affect hosts by causing improved or poor health
states. For example, gut bacteria can provide nutrients or protection to the host, but also
can be pathogenic and cause poor intestinal function. Intestinal microbial composition is
relatively stable during adulthood, but it may begin to be less stable and more variable with
age. Recent advances in sequencing technology have allowed us to better understand how
manipulation of the types of bacteria, and their genes may lead to healthy aging of the host.
However, this work is complicated by the large inter-individual variability in aged subjects,
and the complexity of the microbiota within intestines of higher organisms. Thus, this project
aims to utilize the model organism C. elegans, a microscopic roundworm, to examine
bacterial responses in different hosts. C. elegans allows for genetic control of both the
bacteria and the hosts to ascertain bacterial gene expression and metabolism. Specifically,
bacteria can form biofilms in response to their host environments, primarily to protect
themselves from external stresses such as host immune responses. We know that bacteria
accumulate in older worms, but less is known about how bacteria form biofilms and whether
biofilm formation affects lifespan. Our proposal examines biofilm formation, expression of
biofilm-related genes during specific steps of formation, and the effect of blocking biofilms
on known models of aging. In C. elegans, models of aging include pathways that act
through insulin signaling, caloric intake, and mitochondrial respiration, all of which may
generate different host environments which affect bacteria. In addition, we examine a
component of the apical membrane of intestines, which interfaces and serves to
communicate with bacteria. In particular, we examine a class of enzymes called ceramide
glucosyltransferases, which make the complex sphingolipid glucosylceramide.
Glucosylceramides have been shown to serve as binding partners for some bacteria and
may mediate biofilm formation. Thus, animals lacking or with increased levels of
glucosylceramide may alter biofilm formation. We hope that this work on host/microbiome
interactions will inform the scientific community on the development of novel treatment
strategies to improve healthy aging via host-microbiota interactions.
