GI Map w/ H Pylori and Zonulin
Quantitative PCR assay for GI pathogens performed on stool, the GI Microbial Assay Plus (GI-MAP)
In the last few decades, DNA analysis has transformed the field of microbiology. The Human Microbiome Project and research around the globe have characterized the GI microbiome. More than ever before, we are keenly aware of the health benefits and disease risks brought about by the microorganisms that inhabit the GI tract. Culture techniques, previously the standard, leave up to 50% of bacterial species virtually invisible!
The GI Microbial Assay Plus (GI-MAP™) was designed to assess a patient’s microbiome from a single stool sample, with particular attention to microbes that cause disease or that disrupt normal microbial balance and contribute to perturbations in the GI flora and contribute to illness.
Zonulin is a protein secreted by intestinal cells that regulates intercellular tight junctions (1, 2). Tight junctions are the connections between epithelial cells that make up the gastrointestinal lining. Zonulin increases intestinal permeability in the jejunum and ileum (3) and is considered a biomarker for barrier permeability (1, 2). Tight junctions can be opened or closed, depending on the physiological need. Zonulin’s role is to open tight junctions in the gut. In the case of enteric infections, high zonulin can “open the floodgates” and flush out bacteria and toxins (1). Certain gut bacteria and gliadin (the main staple protein from wheat) can activate the zonulin system (2, 4).
The intestinal barrier is a critical interface between the lumen of the gut and the internal milieu. Dysfunction of this barrier is believed to initiate immune dysfunction because it allows macromolecules from the gut lumen to pass into the bloodstream (5). Intestinal permeability, also known as “leaky gut,” has been associated with inflammatory bowel disease, celiac disease, food allergy, irritable bowel syndrome, critical illness, autoimmune diseases (6) and obesity and metabolic disease (7). In many cases, permeability precedes disease (1).
Zonulin regulates barrier permeability. Serum zonulin correlates with intestinal permeability and lactulose/mannitol tests for intestinal permeability (3, 8). High serum zonulin has been associated with celiac disease, type 1 diabetes (8) insulin resistance and type I diabetes (3), cancers, neurological conditions, and autoimmune diseases (see Table 1) (1).
1. Fasano A. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2012;10(10):1096-1100.
2. Lamprecht M, Bogner S, Schippinger G, et al. Probiotic supplementation affects markers of intestinal barrier, oxidation, and inflammation in trained men; a randomized, double-blinded, placebo-controlled trial. Journal of the International Society of Sports Nutrition. 2012;9(1):45.
3. Stenman LK, Lehtinen MJ, Meland N, et al. Probiotic With or Without Fiber Controls Body Fat Mass, Associated With Serum Zonulin, in Overweight and Obese Adults-Randomized Controlled Trial. EBioMedicine. 2016;13:190-200.
4. Fasano A, Sapone A, Zevallos V, Schuppan D. Nonceliac gluten sensitivity. Gastroenterology. 2015;148(6):1195-1204.
5. Fasano A. Leaky gut and autoimmune diseases. Clinical reviews in allergy & immunology. 2012;42(1):71-78.
6. Fasano A. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living life on the edge of the wall. The American journal of pathology. 2008;173(5):1243-1252.
7. Bischoff SC, Barbara G, Buurman W, et al. Intestinal permeability--a new target for disease prevention and therapy. BMC gastroenterology. 2014;14:189.
8. Wang L, Llorente C, Hartmann P, Yang AM, Chen P, Schnabl B. Methods to determine intestinal permeability and bacterial translocation during liver disease. J Immunol Methods.2015;421:44-53.
9. Wang W, Uzzau S, Goldblum SE, Fasano A. Human zonulin, a potential modulator of intestinal tight junctions. Journal of cell science. 2000;113 Pt 24:4435-4440.
10. Lamprecht M, Bogner S, Steinbauer K, et al. Effects of zeolite supplementation on parameters of intestinal barrier integrity, inflammation, redoxbiology and performance in aerobically trained subjects. Journal of the International Society of Sports Nutrition. 2015;12:40.