Gut Microbiota Remodeling and Intestinal Adaptation to Lipid Malabsorption After Enteroendocrine Cell Loss in Adult Mice.
Gut Microbiota Remodeling and Intestinal Adaptation to Lipid Malabsorption After Enteroendocrine Cell Loss in Adult Mice.
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DOI：
10.1016/j.jcmgh.2023.02.013
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发表时间：
2023
影响因子：
7.2
通讯作者：
Gradwohl, Gerard
中科院分区：
文献类型：
--
作者：
Blot, Florence;Marchix, Justine;Ejarque, Miriam;Jimenez, Sara;Meunier, Aline;Keime, Celine;Trottier, Camille;Croyal, Mikael;Lapp, Celine;Mahe, Maxime M.;De Arcangelis, Adele;Gradwohl, Gerard
肠内分泌细胞(EECS)及其激素是全身能量平衡的重要调节因子。EECS感知腔内营养物质和微生物代谢物，随后分泌各种激素，在本地或远处发挥作用。胚胎发育过程中EECS的发育受损对新生小鼠和人类来说都是危及生命的，因为营养吸收受到了影响。然而，EEC系统在成年小鼠中的生理重要性尚未得到直接研究。在这里，我们的目标是确定在健康成年人中完全丧失EECS对能量代谢、肠道转录组和微生物区系的长期影响。我们用他莫昔芬处理成年Neurog3fl/fl；Villin-CreERT2雄性小鼠，耗尽肠上皮细胞。我们研究了缺乏EECS的小鼠近端和远端小肠的肠道细胞分化、食物效率、脂肪吸收、微生物区系组成、粪便代谢物和转录反应。我们还检测了高脂饮食诱导的Neurog3eYFP/+EECs转录水平的变化。除非以高脂肪饮食喂养，否则导致成人EEC缺乏症不会危及生命。在标准饮食下，由于食物效率受损，小鼠体重减轻了10%。血液中胆固醇、甘油三酯和游离脂肪酸的浓度降低，脂肪在远端小肠的吸收受到损害和延迟。控制脂肪生成、碳水化合物代谢和新糖生成的基因上调。微生物区系组成在EECS耗尽后迅速改变，其特征是α多样性降低。类杆菌和乳杆菌逐渐丰富，而乳螺科减少，不影响粪便短链脂肪酸浓度。在标准饮食下，EECs对于成年雄性小鼠的生存来说是必不可少的。EECS的缺乏会损害肠道的脂质吸收，导致转录和代谢适应以及肠道微生物区系的重塑。
Enteroendocrine cells (EECs) and their hormones are essential regulators of whole-body energy homeostasis. EECs sense luminal nutrients and microbial metabolites and subsequently secrete various hormones acting locally or at a distance. Impaired development of EECs during embryogenesis is life-threatening in newborn mice and humans due to compromised nutrient absorption. However, the physiological importance of the EEC system in adult mice has yet to be directedly studied. Herein, we aimed to determine the long-term consequences of a total loss of EECs in healthy adults on energy metabolism, intestinal transcriptome, and microbiota. We depleted intestinal EECs by tamoxifen treatment of adult Neurog3fl/fl; Villin-CreERT2 male mice. We studied intestinal cell differentiation, food efficiency, lipid absorption, microbiota composition, fecal metabolites, and transcriptomic responses in the proximal and distal small intestines of mice lacking EECs. We also determined the high-fat diet-induced transcriptomic changes in sorted Neurog3eYFP/+ EECs. Induction of EEC deficiency in adults is not life-threatening unless fed with a high-fat diet. Under a standard chow diet, mice lose 10% of weight due to impaired food efficiency. Blood concentrations of cholesterol, triglycerides, and free fatty acids are reduced, and lipid absorption is impaired and delayed in the distal small intestine. Genes controlling lipogenesis, carbohydrate metabolism, and neoglucogenesis are upregulated. Microbiota composition is rapidly altered after EECs depletion and is characterized by decreased α-diversity. Bacteroides and Lactobacillus were progressively enriched, whereas Lachnospiraceae declined without impacting fecal short-chain fatty acid concentrations. EECs are dispensable for survival in adult male mice under a standard chow diet. The absence of EECs impairs intestinal lipid absorption, leading to transcriptomic and metabolic adaptations and remodeling of the gut microbiota.
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DOI：
10.1038/nrmicro3552
发表时间：
2016-01
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Donaldson GP;Lee SM;Mazmanian SK
通讯作者：
Mazmanian SK
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
6.5
作者：
Chalhoub G;Kolleritsch S;Maresch LK;Taschler U;Pajed L;Tilp A;Eisner H;Rosina P;Kien B;Radner FPW;Schicho R;Oberer M;Schoiswohl G;Haemmerle G
通讯作者：
Haemmerle G
影响因子：
5.6
作者：
Barchetta I;Baroni MG;Melander O;Cavallo MG
通讯作者：
Cavallo MG
影响因子：
64.5
作者：
Beumer, Joep;Puschhof, Jens;Clevers, Hans
通讯作者：
Clevers, Hans