Dysbiosis-Associated Change in Host Metabolism Generates Lactate to Support Salmonella Growth.
Dysbiosis-Associated Change in Host Metabolism Generates Lactate to Support Salmonella Growth.
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DOI：
10.1016/j.chom.2017.11.006
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发表时间：
2018-01-10
影响因子：
30.3
通讯作者：
Winter SE
中科院分区：
文献类型：
--
作者：
Gillis CC;Hughes ER;Spiga L;Winter MG;Zhu W;Furtado de Carvalho T;Chanin RB;Behrendt CL;Hooper LV;Santos RL;Winter SE
在沙门氏菌引起的胃肠炎期间，粘膜炎症创造了一个有利于病原体种群在微生物群上扩张的生态位。在这里，我们发现鼠伤寒沙门氏菌感染伴随着生态失调，肠道内丁酸盐水平下降，乳酸水平显著升高。给药乳酸脱氢酶抑制剂使无菌小鼠的乳酸产生钝化，这表明乳酸主要来自宿主。通过口服抗生素治疗或作为病原体诱导的生态失调的一部分，产生丁酸梭菌的消耗触发了宿主细胞从氧化代谢到乳酸发酵的转换，增加了乳酸水平和乳酸沙门氏菌的利用。施用三丁酸甘油酯或PPARγ激动剂会减少宿主乳酸的产生，并取消沙门氏菌利用乳酸的适应性优势。我们的结论是，肠道菌群的改变，特别是梭状芽孢杆菌的消耗，重新编程宿主代谢以进行乳酸发酵，从而支持沙门氏菌感染。鼠伤寒沙门氏菌的肠道感染导致炎症诱导的生态失调。Gillis等人证明，共生梭菌的消耗会降低丁酸盐的利用率，并随后改变宿主产生乳酸的代谢。沙门氏菌的乳酸氧化增强了肠道的适应性，使病原体能够与微生物群竞争。
During Salmonella-induced gastroenteritis, mucosal inflammation creates a niche that favors the expansion of the pathogen population over the microbiota. Here, we show that S. Typhimurium infection was accompanied by dysbiosis, decreased butyrate levels, and substantially elevated lactate levels in the gut lumen. Administration of a lactate dehydrogenase inhibitor blunted lactate production in germ-free mice, suggesting that lactate was predominantly of host origin. Depletion of butyrate-producing Clostridia, either through oral antibiotic treatment or as part of the pathogen-induced dysbiosis, triggered a switch in host cells from oxidative metabolism to lactate fermentation, increasing both lactate levels and Salmonella lactate utilization. Administration of tributyrin or a PPARγ agonist diminished host lactate production and abrogated the fitness advantage conferred to Salmonella by lactate utilization. We conclude that alterations of the gut microbiota, specifically a depletion of Clostridia, reprogram host metabolism to perform lactate fermentation, thus supporting Salmonella infection. Intestinal infection with Salmonella Typhimurium results in inflammation-induced dysbiosis. Gillis et al. demonstrate that depletion of commensal Clostridia reduces butyrate availability and subsequently alters host metabolism to produce lactate. Lactate oxidation by Salmonella enhances fitness in the gut and allows the pathogen to outcompete the microbiota.
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影响因子：
3.6
作者：
Bjerrum, Jacob Tveiten;Wang, Yulan;Hao, Fuhua;Coskun, Mehmet;Ludwig, Christian;Guenther, Ulrich;Nielsen, Ole Haagen
通讯作者：
Nielsen, Ole Haagen
影响因子：
30.3
作者：
Kelly CJ;Zheng L;Campbell EL;Saeedi B;Scholz CC;Bayless AJ;Wilson KE;Glover LE;Kominsky DJ;Magnuson A;Weir TL;Ehrentraut SF;Pickel C;Kuhn KA;Lanis JM;Nguyen V;Taylor CT;Colgan SP
通讯作者：
Colgan SP
DOI：
10.1126/science.aam9949
发表时间：
2017-08-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Byndloss MX;Olsan EE;Rivera-Chávez F;Tiffany CR;Cevallos SA;Lokken KL;Torres TP;Byndloss AJ;Faber F;Gao Y;Litvak Y;Lopez CA;Xu G;Napoli E;Giulivi C;Tsolis RM;Revzin A;Lebrilla CB;Bäumler AJ
通讯作者：
Bäumler AJ
影响因子：
3.2
作者：
BERKOWIT.D;HUSHON, JM;AMES, BN
通讯作者：
AMES, BN
影响因子：
3.2
作者：
GUTNICK, D;CALVO, JM;AMES, BN
通讯作者：
AMES, BN