Microbiota small molecules correlate with Inflammatory Bowel Disease (IBD) pathogenesis, yet the molecular mechanisms behind remain elusive. We recently developed gene manipulation tools in multiple gut Clostridia commensals, and by mutating the responsible gene and mono-colonizing germ-free mice with the mutant, we can switch specific microbiota metabolites on/off in vivo and found that metabolites derived […]
Diet plays a unique role in Crohn’s disease (CD) pathogenesis and therapy. In pediatric CD, commercial formulas used as exclusive enteral nutrition (EEN) are effective at inducing both clinical and biochemical remission. This study assesses the impact of a whole-food blended smoothie as EEN on CD activity and the intestinal microbiome. The primary aims of […]
Patients with Inflammatory Bowel Disease (IBD) can experience many years of inflammation and remission in the gastrointestinal tract. As a result, the intestines can undergo a structural change known as fibrosis, which narrows the inside. This narrowing is a major, and sometimes life-threatening, health issue for patients because it can block the passage of digested […]
Our gut microbiome has a strong influence on a variety of diseases, including Inflammatory Bowel Disease (IBD). Fungi form an integral part the human gut microbiome, and studies in mice showed that fungi may have a substantial influence on inflammation and IBD development, while antibody responses against fungi constitute important clinical IBD diagnostic tools. However, […]
Crohn’s disease is a chronic inflammatory disease of the intestinal tract. It has been increasingly appreciated that two factors are involved beyond the genetic setup of individuals: 1) Intestinal microbial dysbiosis and 2) immune system dysregulation. Intestinal microbial dysbiosis refers to changes in the billions of bacteria that are growing in our gut. In healthy […]
Diet is thought to be a major environmental factor contributing to Inflammatory Bowel Disease (IBD) and represents a non-invasive path to improve this debilitating condition. To leverage diet to treat IBD the precise ways that dietary components influence development or healing of inflammation need to be determined. We discovered that different dietary protein sources have […]
Accumulating data supports the concept that Inflammatory Bowel Disease (IBD) has a preclinical period that may be amenable to early diagnosis and intervention. Understanding the molecular underpinnings of this preclinical period in disease pathogenesis offers new opportunities in risk prediction and prevention. We have recently reported the first data from a large study using longitudinal […]
Recently there has been increased evidence that patients with Crohn’s disease (CD) commonly have disrupted sleep, and disrupted sleep correlates with the risk of disease flare. The sleep/wake cycle, immune function, and multiple biological processes are orchestrated by the circadian clock. The central circadian clock in the brain entrains these processes to the environment by […]
The microbes that flourish within our guts are central to many aspects of human health. Which microbes are present can dictate susceptibility to a number of acute and chronic diseases, including IBD. This proposal will use a mouse model with a defined and stable set of bacteria to probe how mice interact with specific members […]
NOD2 was the first and to date the most frequent gene associated with Inflammatory Bowel Disease (IBD). The NOD2 protein functions as a sensor of bacteria by binding molecules (peptidoglycans) shed from the bacterial cell wall. The IBD mutations in NOD2 result in its inactivation or partial loss of function. In 2019 we reported that […]
