Grant Abstract: Hyaluronan Matrices in Vascular Pathologies

Grant Number: 5P01HL107147-05
PI Name: Hascall
Project Title: Hyaluronan Matrices in Vascular Pathologies

Abstract: The presence of low levels of circulating bacterial products are now thought to contribute to multiple
pervasive conditions that affect a large proportion of the United States population, such as obesity, diabetes,
asthma, atherosclerosis and fatty liver disease. The products can be bacterial cells themselves or
components such as LPS, or metabolites created by fermentation in the bacterial environment that enter
across the intestinal epithelial barrier and travel to extra-intestinal areas. The intestinal microbiome, or the
deverse resident microbial population that lives in the gut, plays a key in what metabolites are produced as
well as the health and permeability of the intestine. Imbalance or ‘dysbiosis’ of the bacteria of the microbiome
contributes to a ‘leaky gut’ and offers less resistance to pathogens. We propose to test a novel oral prebiotic
supplement, modeled after a beneficial component of human milk, hyaluronan (HA), in a human pilot study.
Pre-clinical data from our group show that oral hyaluronan (HA) supplements can shift the microbiome to
contain more of the Bacteroidetes family (S24-7) that are associated with resistance to obesity, diabetes and
Inflammation in mice. In addition the same HA supplements protect against bacterial colitis, infection with
Salmonella Typhimurium as well as a rodent model of enteropathogenic E. coli. Furthermore administration
of oral HA supplements to mice reduces bacterial pathogen translocation to lymph nodes. We think that
specific HA supplement, by modifying the human intestinal microbiome, will foster overall health and
attenuate the development of common non-communicable diseases.

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