Bile acid composition regulates the manganese transporter Slc30a10 in intestine

Ahmad, Tiara R.; Higuchi, Shunichi; Bertaggia, Enrico; Hung, Allison; Shanmugarajah, Niroshan; Guilz, Nicole C.; Gamarra, Jennifer R.; Haeusler, Rebecca A.

doi:10.1101/2020.02.11.944124

Cited by 1 publication

(1 citation statement)

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“…It is very likely to depend on the bioavailability of biliary Mn both to the host and the resident microbes, but this has not been explored. Recently, ileal Mn excretion via Znt10 was shown to be dependent on bile acid composition, suggesting that there is an interplay between Mn homeostasis and bile acids, but how this connects to biliary Mn fluxes in illness remains to be clarified (22). In our data, unexpectedly, biliary Mn was the most increased when the mice were fed the Mn-adequate purified chow that decreased baseline hepatic Mn levels.…”

Section: Discussionmentioning

confidence: 48%

Hepatobiliary manganese homeostasis is dynamic in the setting of illness in mice

Sunuwar

Tomar

Wildeman

et al. 2023

Preprint

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Manganese is a diet-derived micronutrient that is essential for critical cellular processes like redox homeostasis, protein glycosylation, and lipid and carbohydrate metabolism. Control of Mn availability, especially at the local site of infection, is a key component of the innate immune response. Less has been elucidated about Mn homeostasis at the systemic level. In this work, we demonstrate that systemic Mn homeostasis is dynamic in response to illness in mice. This phenomenon is evidenced in male and female mice, mice of two genetic backgrounds (C57/BL6 and BALB/c), in multiple models of acute (dextran sodium sulfate-induced) and chronic (enterotoxigenic Bacteriodes fragilis) colitis, and systemic infection with Candida albicans. When mice were fed a standard corn-based chow with excess Mn (100 ppm), liver Mn decreased and biliary Mn increased 3-fold in response to infection or colitis. Liver iron, copper, and zinc were unchanged. When dietary Mn was restricted to minimally adequate amounts (10ppm), baseline hepatic Mn levels decreased by approximately 60% in the liver, and upon induction of colitis, liver Mn did not decrease further, however biliary Mn still increased 20-fold. In response to acute colitis, hepatic Slc39a8 mRNA (gene encoding the Mn importer, Zip8) and Slc30a10 mRNA (gene encoding the Mn exporter, Znt10) are decreased. Zip8 protein is decreased. Illness-associated dynamic Mn homeostasis may represent a novel host immune/inflammatory response that reorganizes systemic Mn availability through differential expression of key Mn transporters with down-regulation of Zip8.

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Section: Discussionmentioning

confidence: 48%