慶應義塾研究者情報データベース

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• 2024年10月

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  継続中

  慶應義塾大学, 薬学部, 助教

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• 2015年04月

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  2021年03月

  慶應義塾大学, 薬学部, 薬学科

  大学, 卒業

• 2021年04月

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  2024年09月

  慶應義塾大学, 薬学研究科

  大学院, 退学

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• ライフサイエンス / 分子生物学

• ライフサイエンス / 細菌学

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• ノンターゲットリピドミクス

• 生理活性物質

• 腸内細菌

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• Secretory phospholipase A2-IIA targets bacterial extracellular vesicles to modulate immune signaling

  Doré E., Bérubé È., Greffard K., Morozumi S., Chénard V., Lemaire G., Allaeys I., Lévesque T., Rudkowska I., Brisson A.R., Lambeau G., Bertrand N., Boissinot M., Arita M., Bilodeau J.F., Isabel S., Boilard E.

  Communications Biology 8 （ 1 ）  2025年12月

  研究論文（学術雑誌）, 共著, 査読有り

  　概要を見る

  Secretory phospholipase A<inf>2</inf>-IIA (sPLA<inf>2</inf>-IIA) is a bactericidal enzyme that hydrolyzes membrane phospholipids, releasing lipid metabolites that can affect inflammation. sPLA<inf>2</inf>-IIA exhibits poor activity toward eukaryotic cells but preferentially targets gram-positive bacterial membranes. While sPLA<inf>2</inf>-IIA is constitutively expressed in the intestine and upregulated by inflammation in various bodily fluids, its precise physiological substrates remain debated. Intriguingly, sPLA<inf>2</inf>-IIA can modulate the intestinal lipidome without altering the microbiota composition. Here, we investigated whether sPLA<inf>2</inf>-IIA could use membranes from bacterial extracellular vesicles (bEVs) as alternative substrates to modulate immune signaling. We found that bEVs from both Staphylococcus aureus and Escherichia coli could mitigate the bactericidal effects of sPLA<inf>2</inf>-IIA on gram-positive bacteria. Enzymatic hydrolysis of bacteria, bEVs and fecal extracellular vesicles released distinct lipid metabolites and differentially impacted Toll-like receptor activation. These findings suggest that sPLA<inf>2</inf>-IIA can use bEVs as substrates and modulate inflammatory signaling through the generation of pathogen-associated molecular patterns, thus linking bacterial lipid metabolism to host immune response. (Figure presented.)

  • Access to Document (DOI)

• The interaction of secreted phospholipase A2-IIA with the microbiota alters its lipidome and promotes inflammation

  Doré E., Joly-Beauparlant C., Morozumi S., Mathieu A., Lévesque T., Allaeys I., Duchez A.C., Cloutier N., Leclercq M., Bodein A., Payré C., Martin C., Petit-Paitel A., Gelb M.H., Rangachari M., Murakami M., Davidovic L., Flamand N., Arita M., Lambeau G., Droit A., Boilard E.

  JCI Insight 7 （ 2 ）  2022年01月

  研究論文（学術雑誌）, 共著, 査読有り

  　概要を見る

  Secreted phospholipase A2-IIA (sPLA2-IIA) hydrolyzes phospholipids to liberate lysophospholipids and fatty acids. Given its poor activity toward eukaryotic cell membranes, its role in the generation of proinflammatory lipid mediators is unclear. Conversely, sPLA2-IIA efficiently hydrolyzes bacterial membranes. Here, we show that sPLA2-IIA affects the immune system by acting on the intestinal microbial flora. Using mice overexpressing transgene-driven human sPLA2-IIA, we found that the intestinal microbiota was critical for both induction of an immune phenotype and promotion of inflammatory arthritis. The expression of sPLA2-IIA led to alterations of the intestinal microbiota composition, but housing in a more stringent pathogen-free facility revealed that its expression could affect the immune system in the absence of changes to the composition of this flora. In contrast, untargeted lipidomic analysis focusing on bacteria-derived lipid mediators revealed that sPLA2-IIA could profoundly alter the fecal lipidome. The data suggest that a singular protein, sPLA2-IIA, produces systemic effects on the immune system through its activity on the microbiota and its lipidome.

  • Access to Document (DOI)

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• 腸内細菌が産生する脂質代謝物の構造と機能

  両角諭、岡橋伸幸、有田誠

  生化学 （日本生化学会）  95 （ 4 ） 428 - 435 2023年08月

  記事・総説・解説・論説等（学術雑誌）, 共著, 筆頭著者

• Structures and functions of the gut microbial lipidome

  Morozumi S., Ueda M., Okahashi N., Arita M.

  Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids 1867 （ 3 ）  2022年03月

  記事・総説・解説・論説等（学術雑誌）, 共著, 筆頭著者,  ISSN  13881981

  　概要を見る

  Microbial lipids provide signals that are responsible for maintaining host health and controlling disease. The differences in the structures of microbial lipids have been shown to alter receptor selectivity and agonist/antagonist activity. Advanced lipidomics is an emerging field that helps to elucidate the complex bacterial lipid diversity. The use of cutting-edge technologies is expected to lead to the discovery of new functional metabolites involved in host homeostasis. This review aims to describe recent updates on functional lipid metabolites derived from gut microbiota, their structure-activity relationships, and advanced lipidomics technologies.

  • Access to Document (DOI)

担当授業科目 【 表示 ／ 非表示 】

担当授業科目 【 表示 ／ 非表示 】

• 英語演習（薬科学科）

  2026年度

• 代謝生化学

  2026年度

• 免疫代謝学特論

  2026年度

• 卒業研究１（薬学科）

  2026年度

• 機能生理学１

  2026年度

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