Vidisha Mohad, PhD, Richard Hodin, MD, and Nima Saedi, PhD | Massachusetts General Hospital and Harvard Medical School
Competition Sponsor: U.S. National Academy of Medicine
Awardee Year: 2020
Aging increases the vulnerability to many gastrointestinal diseases and is associated with the chronic inflammation, referred to as inflammaging. Aging- associated alteration in the microbiota has been associated with increased gut permeability and increased barrier dysfunction. Although the microbiome has been established as an important regulator of homeostasis, the role of the intestinal alkaline phosphatase (IAP, brush border enzyme secreted into the intestinal lumen by enterocytes) a in regulation of the commensal bacteria in aging gut is largely unknown. Our goal is to advance the knowledge of IAP-microbiota relationship and identifying mechanism of microbial modulation to improve epithelial barrier function. The overall aim of this proposal is to investigate the role of IAP in barrier function by enhancing the healthy gut microbiome in a microfluidic intestine-on-a-chip model. The novel intestine-on-a-chip model will allow a stable coculture of the anaerobic and aerobic microbial communities along with the mucus producing intestinal epithelium derived from primary mouse epithelial cells. We will first elucidate how the aging-induced microbial dysbiosis results in an increased gut permeability and epithelial barrier dysfunction. As a second aim, we will determine how IAP contributes to the crosstalk between the aged microbiome and aging-induced gut barrier dysfunction. Determination relationship between IAP, age-related intestinal barrier dysfunction, and microbiota dysbiosis will help in novel breakthrough approach to prevent a variety of aging-related diseases in humans.
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