Abstract
The effect of limonoids and spermine (Spm) extracted from yuzu (Citrus junos) seeds on the gut and the brain in a mouse model with Sandhoff disease (SD) was investigated. Wild-type and SD mice were fed a normal diet, or a diet supplemented with limonoid, Spm, or limonoid + Spm for 14–18 weeks, and then 16S rRNA gene amplicon sequencing with extracted DNA from their feces was executed. For SD control mice, intestinal microbiota was mostly composed of Lactobacillus and linked to dysbiosis. For SD and wild-type mice fed with limonoids + Spm or limonoids alone, intestinal microbiota was rich in mucin-degrading bacteria, including Bacteroidetes, Verrucomicrobia, and Firmicutes, and displayed a higher production of short-chain fatty acids and immunoglobulin A. Additionally, SD mice fed with limonoids + Spm or limonoids alone had less inflammation in hypothalamic tissues and displayed a greater number of neurons. Administration of limonoids and/or Spm improved the proportions of beneficial intestinal microbiota to host health and reduced neuronal degeneration in SD mice. Yuzu seed limonoids and Spermine may help to maintain the homeostasis of intestinal microbiota and hypothalamic tissue in the SD mouse model.
Highlights
Lysosomal storage disorders are progressive, single-gene disorders that are characterized by reduced enzyme activity and the accumulation of toxins in cells [1]
To identify intestinal microbiota that might be involved in butyric acid metabolism, we focused on bacteria belonging to the Clostridiales group
We found that the relative abundance ratio of the Clostridiales order group found in the feces of both standard deviation (SD) and wild-type mice (WT mice) fed limonoids + Spm were larger than other mice
Summary
Lysosomal storage disorders are progressive, single-gene disorders that are characterized by reduced enzyme activity and the accumulation of toxins in cells [1]. Sandhoff disease (SD) is one of a lysosomal storage disorder characterized by the absence of β-hexosaminidase and accumulate of GM2 ganglioside and related glycolipids GA2 in the central nervous system [2,3,4,5]. In SD mice models, extensive oxidative damage has been observed within the caudal regions in the brain [6,7]. Our team previously demonstrated that treatment with limonoids or spermine (Spm) from yuzu seeds increased survival in SD mice [1]. Recent investigations on the benefits of limonoids or Spm as natural compounds have revealed that they have antitumor, antiinflammatory, and antioxidant properties [8,9,10], with the Spm notably implicated in
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