Micro-Guests' Role in Pathologic Processes

Newswise — We host more microbiota than our own cells. These micro-guests produce metabolites that are only beginning to be appreciated as important factors in pathologic processes, from chronic inflammatory diseases to preterm birth. In this morning’s President’s Invited Session, Gary Wu, MD, and Rebecca Simmons, MD, both from the University of Pennsylvania, will share the most recent findings and ongoing trials that are beginning to define the complex host-guest relationship in inflammatory bowel disease (IBD) and pre-term birth.

The gut environment has a starring role in IBD’s chronic inflammatory disease process, and Wu’s research supports the idea that both diet and gut microbiota greatly influence this environment. Genetic host factors also predispose IBD but appear to have less influence in the development of this disease. IBD features a deeply altered gut microbiota composition, which in turn changes the gut’s environment so that it may help perpetuate the chronicity of this disease. Wu seeks to modify the gut environment and its microbiota with the goal of developing novel interventions to treat and/or prevent IBD.

A clinically effective dietary intervention specifically for Crohn’s disease (a form of IBD) is exclusive enteral nutrition (EEN), which consists of amino acids, simple carbohydrates, and triglycerides. This elemental diet with no other food intake, is highly efficacious, but the mechanisms responsible for this response remain undefined. Using EEN as a therapeutic probe, Wu hopes to identify the biological mechanisms that underlie this response as a modality to define better diets for patients with IBD.

Wu asks, “Are we providing something beneficial in EEN that is halting disease, or are we excluding something that was exacerbating or causing the disease?” He plans to share a strategy for a study in human subjects evaluating the potential role of dietary emulsifiers in the composition and/or function of the gut microbiome as one example of how dietary modifications may be involved in disease pathogenesis.

The environment of the fetus is key to health outcomes decades later, and Simmons is working to determine how a mother’s microbiome may impact her fetus. It has long been known that pre-term birth is associated with cognitive and motor defects in childhood. However, data are accumulating that demonstrate that pre-term birth is also associated with the development of insulin resistance and increased visceral fat deposition later in life.

These findings indicate that much like inter-uterine growth restriction, pre-term birth may increase risk for cardiovascular disease, stroke, Type 2 diabetes, and other chronic diseases. Simmons will discuss new research from the March of Dimes-funded Prematurity Research Center at the University of Pennsylvania showing changes in the vaginal microbiome and metabolome in women who go on to deliver preterm babies.

“Metabolic instruction of immunity is well described in cancer but has not been described in pre-term birth,” she says, which leads to the hypothesis that the maternal microbiota metabolites affect metabolism in both mom and baby, possibly signaling to immune cells to initiate preterm birth.

Simmons will also highlight the controversy surrounding a possible microbiome in the placenta—an improbable evolutionary outcome—and guide the audience through the subtle difficulties in microbiome research. The potential for unrelated environmental contamination in these studies requires rigorous controls, as evidenced by subsequent studies that found no microbiome in the placenta. 

The specific metabolites created by these micro-guests and their effect on human disease is far from clear, but these promising human studies will continue to shed light on this long overlooked symbiosis.