This guest blog is provided by Kristine Klos, PhD, Minnesota Department of Health
An engaging panel including Gary Perdew and Andrew Patterson from Pennsylvania State University, Charlie Knutson from Massachusetts Institute of Technology, Peter Turnbaugh from University of California-San Francisco, and Andrew Gerwirtz from Georgia State University shared their work with us Wednesday morning in the session “Role of the Gut Microbiome in the Host Response to Xenobiotics.” These presentations focused on the complicated roles our gut microbes play in metabolizing drugs and chemicals. Many substances affect the homeostasis of the gut microbiome. This includes food, pesticides, cosmetics, pollutants, and drugs. When the balance of gut microbiota is disturbed, metabolism is disturbed, and a key consequence is the production of inflammatory cytokines.
Two of the presentations focused on the Aryl Hydrocarbon Receptor (AhR). The AhR is a main metabolic player in both the host and gut microbiome. The AhR is a ligand activated transcription factor that binds xenobiotics, dietary metabolites, and microbiotic metabolites. It is expressed in essentially every cell in the intestinal tract. It is involved in the regulation of cytokines, chemokines, growth factors, and energy homeostasis. The AhR plays a critical role in gut homeostasis. This involves maintaining epithelial barrier function in the gut. The binding of ligand can either be beneficial in maintaining a healthy mucosal barrier, or be deleterious resulting in inflammation and changes in the gut microbiota.
Inflammatory diseases, such as Inflammatory Bowel Disease (including Crohn’s Disease and ulcerative colitis), and Metabolic Syndrome are linked to the gut microbiome. Metabolic Syndrome is characterized by abnormalities associated with insulin resistance and obesity. It is also associated with inflammation in the gut, the remodeling of adipose tissue, and alterations in the gut microbiota. Metabolic syndrome is characterized by increased caloric consumption, followed by nutrient excess, endoplasmic reticulum stress, pro-inflammatory signaling, and desensitization of the insulin receptor signaling. Increasing evidence shows that the gut microbiota are essential to the pro-inflammatory signaling of Metabolic Syndrome. Altering the gut microbiota could be a potential therapeutic target.
It was brought to our attention that in the last 50 years, although the incidence of metabolic syndrome has increased, our genetics have not changed. Influences on the gut microbiome have been suspected to be involved in this increased incidence. These influences include our use of antibiotics, increased hygiene, altered macro- and micro- nutrients, and the use of emulsifiers in our food. In fact, two emulsifiers found in our food, Polysorbate 80 and Carboxymethylcellulose, change the composition of the gut microbiome. Mice exposed to these emulsifiers presented with increased inflammation and a reduction of the mucosal barrier in the gut, colitis, and metabolic syndrome.
Recurring themes presented this morning centered on the complex nature of microbiotic interactions in the gut, and inflammation as a result of changes in the microbiotic populations. Altering the inflammatory response of gut microbiota may provide potential therapeutic interventions for a number of inflammatory disorders.
This blog discusses highlights from the SOT Annual Meeting and ToxExpo Symposium Session “Role of the Gut Microbiome in the Host Response to Xenobiotics.”