Chris Kresser: Beta-glucuronidase is definitely associated with higher levels of colon and breast cancer. We have to be careful in saying that. It means if it’s high, the patient definitely has a higher risk. If you understand association, these kind of association studies, it does mean that the chances are higher, but it doesn’t mean that it’s true in every person. There are certainly patients who have higher levels of that who won’t go onto have cancer, but it does indicate that something is off in the gut, and we want to do things to fix the dysbiosis and disrupted gut microbiome so that marker comes down. You will typically see that marker come down as you address the underlying causes in the gut. I think that is a useful marker. Zonulin is a marker for intestinal permeability. It was discovered by Alessio Fasano. It’s thought to indicate the presence of intestinal permeability, the presence of chronic inflammation and disease, but there’s some really confusing stuff out there. First of all, zonulin is a highly variable marker. It can change as it has a half-life and four to six hours if I remember correctly, so that means it can change a lot throughout the day. That’s true for serum zonulin. I’m not sure what the half-life is for fecal zonulin. I was just like doing some research on fecal zonulin in particular, and there was a study that found that fecal zonulin levels went up after the patients who were on a standard kind of industrialized diet were switched to an Okinawan-based Nordic diet, which is nutrient-dense, whole-foods diet with higher levels of dietary fiber and also lower carbohydrate content and a little bit higher protein intake. In this particular study, levels of zonulin, calprotectin, and other inflammatory markers went up in the feces after the introduction of this diet. It’s a really interesting study, and the free text is available online, but the speculation was that the serum levels of these biomarkers may depend more on protein content of the food since they correlate with the percentage of energy derived from protein than they do on inflammation per se because this diet has been shown convincingly to be anti-inflammatory, much less inflammatory than standard American or standard industrialized diet, and yet these markers went up, which might at least on the surface, suggests increase in inflammation. I think the more you get into this, the more you’ll find the devils in the details. There’s often a lot of nuance to these studies and even to the mechanisms and understanding this stuff takes time, and you can’t just accept the conclusion of a study at face value. You really have to dig in and look at the details and understand the mechanism. All of that said, zonulin may be a marker for intestinal permeability in some cases, but I would take it with a grain of salt at this point because I think more work needs to be done on understanding intra-individual variability and figuring out what it really means to see a single elevation of zonulin in the serum or on a fecal test.