Biology subjects

Lee, M.-T.

Publications and source records attributed to Lee, M.-T..

4 recordsLinked to original sources

bioRxiv2026

Dietary omega-3 polyunsaturated fatty acids interact with select gut microbes to produce bioactive metabolites found in infant gut metabolomes

Gut microbes metabolize nutrients in infant diets, producing compounds that play roles in host health. Long-chain polyunsaturated fatty acids (LCPUFAs) are an important component of infant diets, supporting neurological development and immune regulation. Emerging evidence demonstrates that gut microbes, alongside the host, participate in the metabolism of dietary lipids, highlighting an underexplored avenue for LCPUFA biology. In this work, alkyne-tagged eicosapentaenoic acid (EPAALK) was used to investigate interactions between LCPUFAs and the gut microbiota. Flow cytometry and comparative metabolomics identified gut microbial EPA interactors in the ileum of mice. Further comparative metabolomics analysis identified the conversion of EPA to N-acyl amino acids, including attachment to phenylalanine (EP-Phe) and leucine (EP-Leu). Targeted analysis of ex vivo stool cultures determined that EP-Phe and EP-Leu are produced by gut bacteria. A survey of lipid-relevant infant gut bacteria determined various flow cytometry-confirmed EPA-microbe interactions and identified Enterococcus faecalis, Bacteroides thetaiotaomicron, and Clostridium bifermentans as competent producers of EP-Phe or EP-Leu. Thus, both novel metabolites from diet-derived inputs and microbial producers of these metabolites were identified. Together, this highlights important microbiome-centric and mechanistic consequences of LCPUFA consumption and emphasizes that the gut microbiome may be an important consideration in targeted supplementation strategies.

microbiology↗

bioRxiv2024

Gut bacterial sphingolipid production modulates dysregulated skin lipid homeostasis

Sphingolipids are an essential lipid component of the skin barrier with alterations in skin sphingolipid composition associated with multiple skin disorders including psoriasis, atopic dermatitis, and ichthyosis. Contributions to skin sphingolipid abundance are not well characterized, thus the main method of modulating skin lipid levels is the topical application of creams rich with sphingolipids at the skin surface. Evidence that diet and gut microbiome function can alter skin biology proposes an intriguing potential for the modulation of skin lipid homeostasis through gut microbial metabolism, but potential mechanisms of action are not well understood. Sphingolipid synthesis by prominent gut microbes has been shown to affect intestinal, hepatic and immune functions with the potential for sphingolipid-producing bacteria to affect skin biology through altering skin sphingolipid levels. To address this question, we used bioorthogonal chemistry to label lipids from the sphingolipid-producing bacteria Bacteroides thetaiotaomicron and trace these lipids to the skin epidermis. Exposing mice to B. thetaiotaomicron strains mutant in the ability to produce sphingolipids resulted in significantly lower transfer of gut microbiome-derived lipids to the skin, while also altering skin biology and altering expression of skin barrier genes. Measurement of skin ceramide levels, a class of sphingolipids involved in skin barrier function, determined that skin sphingolipid levels were altered in the presence of gut sphingolipid-producing bacteria. Together this work demonstrates that gut bacterial lipids can transfer to the skin and provides a compelling avenue for modulating sphingolipid-dominant compartments of the skin using sphingolipid-producing bacteria of the gut microbiome.

microbiology↗

bioRxiv2021

Metal transporter SLC39A14/ZIP14 modulates regulation between the gut microbiome and host metabolism

Zinc (Zn) plays a critical role in maintaining intestinal homeostasis by regulating intestinal epithelial cells, host immune cells, and gut microbiome community composition. Deletion of metal transporter Slc39a14/Zip14 causes spontaneous intestinal permeability with low-grade chronic inflammation, mild hyperinsulinemia, and greater body fat with insulin resistance in adipose, suggesting a role for ZIP14-mediated intestinal metal transport in regulating both intestinal homeostasis and systemic metabolism. Here, we showed the function of ZIP14-mediated Zn transport in the gut microbiome composition and how ZIP14-linked changes to gut microbiome community composition are correlated with changes in host metabolism. Deletion of Zip14 generated Zn-deficient epithelial cells and luminal content in the entire intestinal tract; reduced bacterial diversity and Saccharomyces cerevisiae (S. cerevisiae) overgrowth; altered host metabolome; and shifted host energy metabolism toward glucose utilization. This work provides evidence for the regulation of gut microbiome composition, host metabolome, and energy metabolism by metal transporter ZIP14. SignificanceIntestinal permeability, gut dysbiosis, and Zn dyshomeostasis are emerging signatures of inflammatory bowel diseases and metabolic disorders such as type-2-diabetes and obesity. Zn deficiency is a common clinical finding among these diseases. Zn is essential for the regulation of the intestinal epithelial cells, host immune cells, and the gut microbiome. Transporter-mediated mobilization of Zn plays a critical role in maintaining intestinal homeostasis by facilitating the targeted tissue/cell-specific function. However, studies are lacking in linking transporter-mediated Zn mobilization, gut microbiome, hosts intestinal health, and metabolism. Using the systems-level approach, this study revealed novel findings that deletion of Slc39a14/Zip14 resulted in altered intestinal Zn homeostasis, gut microbiome composition, host metabolome and energy metabolism.

physiology↗

bioRxiv2020

Dietary sphinganine is selectively assimilated by members of the gut microbiome

Functions of the gut microbiome have a growing number of implications for host metabolic health, with diet being one of the most significant influences on microbiome composition. Compelling links between diet and the gut microbiome suggest key roles for various macronutrients, including lipids, yet how individual classes of dietary lipids interact with the microbiome remain largely unknown. A class of lipids known as sphingolipids are bioactive components of most foods and are produced by prominent gut microbes. This makes sphingolipids intriguing candidates for shaping diet-microbiome interactions. Here, we use a click-chemistry based approach to track the incorporation of bioorthogonal dietary omega-alkynyl sphinganine (sphinganine alkyne - SAA) into the gut microbial community (Click). Identification of microbe and SAA-specific metabolic products was achieved by fluorescence-based sorting of SAA containing microbes (Sort), 16S rRNA gene sequencing to identify the sphingolipid-interacting microbes (Seq), and comparative metabolomics to identify products of SAA assimilation by the microbiome (Spec). Together this approach, Click-Sort-Seq-Spec (ClickSSS), revealed that SAA-assimilation was nearly exclusively performed by gut Bacteroides, indicating that sphingolipid-producing bacteria play a major role in processing dietary sphinganine. Comparative metabolomics of cecal microbiota from SAA-treated mice showed conversion of SAA to a suite of dihydroceramides, consistent with metabolic activity via Bacteroides and Bifidobacterium. Additionally, other sphingolipid-interacting microbes were identified with a focus on an uncharacterized ability of Bacteroides and Bifidobacterium to metabolize dietary sphingolipids. Therefore, ClickSSS provides a platform to study the flux of virtually any alkyne-labeled metabolite in diet-microbiome interactions.

microbiology↗