Certain studies suggest that, patients with DAO deficiency, present an imbalance or dysbiosis of the intestinal microbiota compared to healthy individuals.

The important role played by the intestinal microbiota in metabolism and, consequently, in the individual health, has contributed to research in the identification of specific microorganisms involved in different processes and metabolic pathways in which they participate. While it is true that there are numerous investigations that have studied the connection between the intestinal microbiota and certain noncommunicable diseases, such as obesity and diabetes, the relationship with DAO deficiency is becoming a new focus of study with promising results.

From AD Dietistas we have interviewed Dr. Sònia Sánchez Pérez, researcher and associate professor of the Nutrition, Food Sciences Department of the Campus de l’Alimentació (Universitat de Barcelona).

It is known that the alteration of the DAO enzyme activity can have a genetic, pharmacological or pathological origin. A recent proposal also suggests that it may arise from an alteration in the intestinal microbiota. Which is the mechanism that connects them?

Currently, there are very few studies that shed light on the role of the intestinal microbiota in histamine intolerance and DAO deficiency. The study carried out by Schink et al. in 2018, in which they compared the composition of the intestinal microbiota between control and histamine-intolerant patients (among other intolerances) suggested that intestinal dysbiosis (or alteration in the composition of the intestinal microbiota) could contribute to inflammation of the intestinal mucosa, which, in turn, could favor a decrease in the DAO enzyme at the intestinal level.

Is there currently any study which has succeeded in characterizing the profile and the composition of the intestinal microbiota of individuals with symptoms of histamine intolerance, comparing it with that of a healthy population?

Yes, they exist, although very few. Specifically, two studies that compared the composition of the intestinal microbiota between healthy individuals (without symptoms of histamine intolerance) and individuals with histamine intolerance compatible symptoms. There is another study carried out by our research group “Bioactive Amines and Polyamines from Food” of the Campus de l’Alimentació (Universitat de Barcelona) in which we observed the evolution of the composition of the intestinal microbiota throughout a low-histamine diet and supplementation with DAO enzyme.

In addition to an alteration in the composition and/or abundance of intestinal bacteria, the integrity of the intestinal barrier also plays a relevant role. High levels of DAO activity in blood, can they suggest the existence of intestinal hyperpermeability?

There are certain studies which establish this relationship, although its mechanism is not well known. To assess whether or not there is elevated intestinal permeability, zonulin in feces is usually used (a protein directly related to this permeability). In this case, Schink et al (2018) observed that fecal zonulin levels in individuals with histamine intolerance were above the reference values for healthy people.

Dietary intervention with a low-histamine diet and/or oral supplementation with the DAO enzyme, which potential effects has it shown or do you think it could show on the composition of the intestinal microbiota?

In this sense, there is only one pilot study carried out by our research group with a small number of patients. In this research, we studied the composition of the intestinal microbiota evolution in histamine intolerant patients throughout the dietary treatment. We observed a change in the profile and the composition of the intestinal microbiota; mainly, a decrease in some bacteria related to the histamine formation. More studies are needed to find out the reason for these changes throughout the dietary treatment of this intolerance. It is a very recent field and there is still much to be investigated.

If you had to design a probiotic for people with DAO deficiency, which strains should be essential and which should be avoided?

Based on the results of the work carried out by Pugin et al. (2017), in which from fecal samples, they identified bacteria that produce and degrade histamine and other amines, those bacteria that seem to be more histaminogenic and, therefore, seem to be strains of the genera Morganella Morganii, Lactobacillus vaginalis, Enterobacter cloacae and Proteus mirabilis, among others, should be avoided in this type of probiotics. According to the results of this study, come strains which may present DAO activity would be Escherichia coli (be careful because it also has histamine-forming strains) and Klebsiella pneumoniae.

From AD Dietistas we thank Dr. Sònia Sánchez-Pérez for having collaborated on this article, contributing her professional experience in this regard.

Bibliography

Pugin, B., Barcik, W., Westermann, P., Heider, A., Wawrzyniak, M., Hellings, P., Akdis, C. A., & O’Mahony, L. (2017). A wide diversity of bacteria from the human gut produces and degrades biogenic amines. Microbial ecology in health and disease, 28(1), 1353881. https://doi.org/10.1080/16512235.2017.1353881

Sánchez-Pérez, S., Comas-Basté, O., Duelo, A., Veciana-Nogués, M. T., Berlanga, M., Latorre-Moratalla, M. L., & Vidal-Carou, M. C. (2022). Intestinal Dysbiosis in Patients with Histamine Intolerance. Nutrients, 14(9), 1774. https://doi.org/10.3390/nu14091774

Sánchez-Pérez, S., Comas-Basté, O., Duelo, A., Veciana-Nogués, M. T., Berlanga, M., Vidal-Carou, M. C., & Latorre-Moratalla, M. L. (2022). The dietary treatment of histamine intolerance reduces the abundance of some histamine-secreting bacteria of the gut microbiota in histamine intolerant women. A pilot study. Frontiers in nutrition, 9, 1018463. https://doi.org/10.3389/fnut.2022.1018463

Schink, M., Konturek, P. C., Tietz, E., Dieterich, W., Pinzer, T. C., Wirtz, S., Neurath, M. F., & Zopf, Y. (2018). Microbial patterns in patients with histamine intolerance. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 69(4), 10.26402/jpp.2018.4.09. https://doi.org/10.26402/jpp.2018.4.09

Schnedl, W. J., & Enko, D. (2021). Histamine Intolerance Originates in the Gut. Nutrients, 13(4), 1262. https://doi.org/10.3390/nu13041262

Smolinska, S., Winiarska, E., Globinska, A., & Jutel, M. (2022). Histamine: A Mediator of Intestinal Disorders-A Review. Metabolites, 12(10), 895. https://doi.org/10.3390/metabo12100895