Contribution of phytochemicals to gut symbiont colonization and synthesis of immunomodulatory sphingolipids

植物化学物质对肠道共生体定植和免疫调节鞘脂合成的贡献

基本信息

批准号：
10624740
负责人：
Sungwhan F Oh
金额：
$ 15.72万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-02-01 至 2024-01-31
项目状态：
已结题

项目摘要

PROJECT SUMMARY Symbiotic microbiota make critical contributions to host immune development. During the first few years of human life, and the first three weeks in mice, the gut microbiota undergoes dramatic transformation, mostly in response to changes in the host environment. How temporal changes and mutual host-microbiota adaptations shape mucosal immunity remains elusive; however, the contribution of environmental factors (such as shifts in diet over the life course) warrants molecular-level investigation of the effects of prebiotics/probiotics. We have previously shown that the ubiquitous human gut symbiont Bacteroides fragilis can modulate host colonic natural killer T (NKT) cell development by producing unique sphingolipids (alpha-galactosylceramides, or BfaGCs). Under our original R01, we characterized human microbiota-associated mice (HMA mice). Supplementation of phytochemicals to HMA mice suppressed colonic NKT cell levels in their offspring. Of note, in adult HMA mice, phytochemical supplementation can transiently induce the abundance of B. fragilis, strongly implying that induction of B. fragilis during pre- and postnatal stages is critical for colonic NKT cell development. In the current proposal, we will dissect the time course of early development and investigate the impact of phytochemicals on the complex microbiota and subsequent mucosal immune development in early life. This study will provide valuable information on the effect of beneficial microbes in pregnancy in response to prebiotic factors, as well as the impact of supplementation during gestation / lactation on the microbiota and immune development of offspring.

项目摘要共生微生物群为宿主免疫发育做出了重要贡献。在最初的几年人类的生活，以及小鼠的头三周，肠道微生物群经历了戏剧性的转变，主要是在对主机环境变化的响应。时间变化和相互宿主微生物的适应形状粘膜免疫仍然难以捉摸；但是，环境因素的贡献（例如转变饮食在生命过程中）保证对益生元/益生菌作用的分子水平研究。我们先前已经表明，无处不在的人类肠道共生菌菌素fragilis可以调节宿主结肠通过产生独特的鞘脂（α-半乳糖基酰胺或 bfagcs）。在我们的原始R01下，我们表征了与人类微生物群相关的小鼠（HMA小鼠）。补充植物化学物质对HMA小鼠的后代抑制了结肠NKT细胞水平。值得注意的是，在成年HMA小鼠中，植物化学补充可以瞬时诱导丰富的脆弱芽孢杆菌，强烈地诱导暗示在产后和产后阶段诱导脆弱的链球菌对于结肠NKT细胞发育至关重要。在当前的提案中，我们将剖析早期发展的时间过程，并调查早期生命的复杂菌群和随后的粘膜免疫发育的植物化学物质。这研究将提供有关对益生元的妊娠中有益微生物在怀孕中的影响的宝贵信息因素，以及妊娠 /泌乳期间补充对微生物群和免疫的影响后代的发展。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Unconventional immune cells in the gut mucosal barrier: regulation by symbiotic microbiota.

DOI：
10.1038/s12276-023-01088-9
发表时间：
2023-09
期刊：
EXPERIMENTAL AND MOLECULAR MEDICINE
影响因子：
12.8
作者：
Yoo, Ji-Sun;Oh, Sungwhan F.
通讯作者：
Oh, Sungwhan F.

ROS-dependent S-palmitoylation activates cleaved and intact gasdermin D.

ROS 依赖性 S-棕榈酰化可激活裂解且完整的gasdermin D。

DOI：
10.1038/s41586-024-07373-5
发表时间：
2024
期刊：
Nature
影响因子：
64.8
作者：
Du,Gang;Healy,LiamB;David,Liron;Walker,Caitlin;El-Baba,TarickJ;Lutomski,CorinneA;Goh,Byoungsook;Gu,Bowen;Pi,Xiong;Devant,Pascal;Fontana,Pietro;Dong,Ying;Ma,Xiyu;Miao,Rui;Balasubramanian,Arumugam;Puthenveetil,Robbins;Bane
通讯作者：
Bane

Kinetic and mechanistic diversity of intestinal immune homeostasis characterized by rapid removal of gut bacteria.