Influence of the gut microbiota and probiotics on selenium metabolism in the rat: In vitro and in vivo studies
Selenium plays a major role in the immune system and in decreasing the risk of cancer. Plasma selenium levels are low in patients with certain gastrointestinal disorders suggesting a role for the gut microbiota in selenium metabolism and disposition. Probiotic treatment can modulate the gut microbiota but the effect of such treatment on the metabolism of selenium supplements is unknown. The present study investigated the metabolism of L-selenomethionine (L-SeMet) and selenite, commonly used as selenium supplements, by probiotic bacteria in vitro and by rat gut contents ex vivo. The effect of probiotic treatment on the disposition of selenium after oral dosing with L-SeMet and selenite in rats was also investigated. After anaerobic incubation of L-SeMet (0.51 mM) with 10% w/w suspensions of the contents of jejunum, ileum, caecum and colon from male Wistar rats at 37°C for 3 h, L-SeMet metabolism (30%) was greatest in caecum contents followed by colon, ileum and jejunum. Dimethyldiselenide (DMDSe) was produced to the extent of 8.7% of the L-SeMet added and 28.9% of the L-SeMet lost. A similar result was obtained after incubation of selenite (0.58 mM) with metabolism being complete in caecum contents and almost complete in colon. Dimethylselenide (DMSe) (5.7% of the selenite added) was produced accompanied by a red precipitate of elemental selenium. When L-SeMet (0.51 mM) was incubated anaerobically with individual antibiotic-resistant probiotic strains (Streptococcus salivarius K12, Lactobacillus rhamnosus 67B, Lactobacillus acidophilus L10 and Bifidobacterium lactis LAFTI® B94) (1 - 5x1010 cfu/mL) and with a mixture of the four probiotic strains (ca. 3x1010 cfu/mL) at 37°C for 24 h, 10 - 18% was metabolised with 36-80% of L-SeMet being converted to DMDSe and DMSe. In similar incubations with selenite (0.58 mM), metabolism was more extensive (26 - 100%) particularly by the lactobacilli with 0-4.8% of selenite being converted to DMSe and DMDSe accompanied by the formation of elemental selenium. Metabolism of L-SeMet or selenite in incubations with a combination of gut contents and the four probiotic strains indicated some suppression of L-SeMet metabolism and enhancement of selenite metabolism. These results suggest probiotics and gut microorganisms interact in relation to selenium metabolism in the gut. In the in vivo study, three groups of rats (n = 3/group) were given saline or a single oral dose of 2 mg selenium/kg as L-SeMet or selenite by gavage (untreated rats). Another four groups of rats (n = 6/group) were given the same dose of either L-SeMet or selenite (2 mg selenium/kg) at the time of the last dose of treatment with 3 mL of a mixture containing equal numbers of the four antibiotic-resistant probiotic strains (total cell count ca. 1x1010 cfu/mL) or vehicle (a mixture of the lyoprotectants trehalose, maltodextrin and lactitol) every 12 h for three days (treated rats). Blood was collected from five rats in each treatment group over 24 h and serum analysed for selenium along with samples of liver and kidney obtained at 24 h. The sixth rat in each treatment group was used to determine the counts of total bacteria and of each of the antibiotic-resistant probiotic strains in the four segments of the gut at 24 h. Serum selenium concentrations over 24 h were not significantly different between probiotic and vehicle treated rats but were more sustained after L-SeMet or significantly higher after selenite than in untreated rats. In the liver and kidney of probiotic treated rats at 24 h, L-SeMet produced a significantly higher selenium level in the liver and lower selenium level in the kidney than in untreated rats. A similar trend was observed in rats given selenite but the differences were not significant. Total bacterial counts in corresponding segments of probiotic and vehicle treated rats were similar to each other and to corresponding counts in normal rats except in jejunum which were 103 - 104 cfu/g higher. In rats treated with probiotics, only L. rhamnosus 67B and L. acidophilus L10 were detected in all gut segments in approximately equal numbers which were 102 - 104 cfu/g less than the corresponding total bacterial counts. The present study indicates that: L-SeMet and selenite are metabolised in rat gut contents ex vivo to form volatile methylated selenium compounds and, in the case of selenite, elemental selenium; probiotic bacteria can metabolise L-SeMet and selenite in a manner similar to the gut microbiota; oral treatment with lyoprotectants stimulates bacterial growth in the gut leading to changes in the metabolism of L-SeMet and selenite; and treatment with probiotics and lyoprotectants exerts an effect on selenium disposition over and above that produced by lyoprotectants alone. Overall these results suggest that the gut microbiota play an important role in metabolising selenium supplements and that treatment with probiotics and lyoprotectants can influence selenium disposition after oral doses of L-SeMet and selenite. Whether these changes indicate a beneficial role for combination treatment with probiotics and selenium supplements requires further research.
Advisor: Fawcett, J. Paul; McDowell, Arlene; Thomson, Christine D.
Degree Name: Doctor of Philosophy
Degree Discipline: School of Pharmacy
Publisher: University of Otago
Keywords: selenium; gut microbiota; probiotics; rat
Research Type: Thesis