Selenium in Human Health and Gut Microflora: Bioavailability of Selenocompounds and Relationship With Diseases

Abstract

This review covers current knowledge of selenium in the dietary intake, its bioavailability, metabolism, functions, biomarkers, supplementation and toxicity, as well as its relationship with diseases and gut microbiota specifically on the symbiotic relationship between gut microflora and selenium status. Selenium is essential for the maintenance of the immune system, conversion of thyroid hormones, protection against the harmful action of heavy metals and xenobiotics as well as for the reduction of the risk of chronic diseases. Selenium is able to balance the microbial flora avoiding health damage associated with dysbiosis. Experimental studies have shown that inorganic and organic selenocompounds are metabolized to selenomethionine and incorporated by bacteria from the gut microflora, therefore highlighting their role in improving the bioavailability of selenocompounds. Dietary selenium can affect the gut microbial colonization, which in turn influences the host's selenium status and expression of selenoproteoma. Selenium deficiency may result in a phenotype of gut microbiota that is more susceptible to cancer, thyroid dysfunctions, inflammatory bowel disease, and cardiovascular disorders. Although the host and gut microbiota benefit each other from their symbiotic relationship, they may become competitors if the supply of micronutrients is limited. Intestinal bacteria can remove selenium from the host resulting in two to three times lower levels of host's selenoproteins under selenium-limiting conditions. There are still gaps in whether these consequences are unfavorable to humans and animals or whether the daily intake of selenium is also adapted to meet the needs of the bacteria.

Keywords: gut microbiota; selenium; selenium metabolism; selenocompounds; selenoproteins.

Figure 1

Foods rich in Se with their relative proportions of SeMet, SeCys, SeMeCys, selenate, selenite, and γ-GluMeSeCys. The figure shows the predominance of SeMet in Brazil nuts, wheat grain, fish cod, and chicken (breast). Lamb meat (kidney) is rich in Se mainly in the SeCys form, whereas onion has Se almost exclusively in the form of selenate. Garlic, potato, and broccoli have a balanced proportion of the various forms of Se. Se, selenium; SeMet, selenomethionine; SeCys, selenocysteine; SeMeCys, selenium-methylselenocysteine; γ-GluMeSeCys, γ-glutamyl-Se-methyl-selenocysteine (Figure illustration by Francisco Irochima Pinheiro).

Figure 2

Main countries with documented Se-rich soils. The presence of Se-rich soil is not uniform in the world, but some countries such as Egypt, China, India, Norway, and USA stand out among the others. On the other hand, some plants are more capable of retaining Se, for example - Bertholletia excelsa (Brazil nuts), which is a typical tree of the northern region of Brazil. Se, selenium; SeMet, selenomethionine; SeCys, selenocysteine (Figure illustration by Francisco Irochima Pinheiro).

Figure 3

Se absorption, metabolism, and distribution. After eating Se-rich foods in its organic and/or inorganic form, Se absorption occurs in the duodenum, cecum, and colon. In enterocytes, SeMet and SeCys are absorbed by active transport (systems B0 and b0 + rBAT) while selenate is absorbed by passive transport (anion changers of the SLC26 gene family). After absorption, all forms of Se are converted to H₂Se through reactions that occur in the enterocyte and transported in the blood bound LDL, VLDL (mainly). In the liver, H₂Se is converted to SePhp and incorporated into selenoproteins in the form of SeCys. Transport to other tissues such as testis, kidneys, and brain occurs mainly in the form of SELENOP through receptor-mediated endocytosis - apoE2 and megaline. Se, selenium; SeMet, selenomethionine; SeCys, selenocysteine; H₂Se, hydrogen selenide; LDL, low-density lipoprotein; VLDL, Very low-density lipoprotein; SePhp, selenophosphate; SELENOP, selenoprotein P; apoE2, apolipoprotein E receptor 2 (Figure illustration by Francisco Irochima Pinheiro).

Figure 4

Se biomarkers. The Se status is evaluated with the purpose of quantifying the biologically active or potentially active nutrient as a function of Se intake, retention, and metabolism in the body. The Se status can be assessed at three levels using specific biomarkers: (1) biomarkers of intake (assessment of food consumption through the food frequency questionnaire); (2) biomarkers of retention/excretion and concentration in tissues (urine, feces, nails, hair, and plasma) and (3) biomarkers of selenium functionality (SELENOP and GPX3 in plasma and GPX1 in erythrocytes, lymphocytes, and tissue samples). Se, selenium; SELENOP, selenoprotein P; GPX1, glutationa peroxidase; GPX3, glutationa peroxidase 3 (Figure illustration by Francisco Irochima Pinheiro).

Figure 5

Modulation of the gut microbiota dependent on Se status and biotransformation of Se derivatives. Given the adequate intake of Se, homeostasis occurs due to the beneficial relationship between intestinal and host bacteria resulting in the biotransformation of Se compounds (Se salts metabolized into SeMet and SeCys). Se deficiency results in increased Se uptake by bacteria (Escherichia coli, Clostridia, and Enterobacteria), biotransformation of Se compounds (Se salts metabolized into SeMet and SeCys), decreased expression of selenoproteins by the host, decreased activation of Se immune cells, increased pro-inflammatory cytokines, and increased risk for IBD and cancer. On the other hand, excessive intake of Se causes increased uptake by bacteria such as Turicibacter, Akkermansi, and Lactic acid bacteria (LAB), biotransformation of Se compounds such as selenite (Se${\text{O}}_3^{2-}$) and selenate (Se${\text{O}}_4^{2-}$) which are metabolized into SeMet and SeCys, and increased excretion of volatile compounds from Se. Se, selenium; SeMet, selenomethionine; SeCys, selenocysteine; IBD, inflammatory bowel diseases (Figure illustration by Francisco Irochima Pinheiro).