腸道微生物菌群的改變可導致很多人類疾病，但是這種改變的機制還不是很清楚。抗生素的使用增加了由傷寒沙門菌導致胃腸炎的風險，延長了病原菌出現在病人糞便中的持續時間，并且有可能導致病原菌和癥狀的復發。這種抗生素導致的微生物菌群的改變在小鼠中得到了驗證：給小鼠飼喂鏈霉素后導致大腸中傷寒沙門菌增殖，然而鏈霉素導致傷寒沙門菌增殖的機制卻不清楚。本文將介紹宿主介導的半乳糖和葡萄糖氧化促進抗生素治療后鼠傷寒沙門菌增殖。鏈霉素治療后，通過增加小鼠盲腸黏膜中誘導性一氧化氮合酶編碼基因表達，增加了小鼠盲腸中氧化產物粘酸和葡萄糖酸的含量。粘酸和葡萄糖酸促進鼠傷寒沙門菌生長，利用基因手段破壞相應的代謝途徑可降低鼠傷寒沙門菌的競爭優勢。研究結果顯示宿主介導的腸道內碳水化合物的氧化是導致抗生素治療后病原菌增殖的作用機制。
Host-mediated sugar oxidation promotes post-antibiotic pathogen expansion
Franziska Faber, Lisa Tran, Mariana X. Byndloss, Christopher A. Lopez, Eric M. Velazquez , Tobias Kerrinnes, Sean-Paul Nuccio, tamding Wangdi, Qliver Fiehn, Renee M. Tsolis & Andreas J. Baumler
doi :10. 1038 / nature 18597
Changes in the gut microbiota may underpin many human diseases, but the mechanisms that are responsible for altering microbial communities remain poorly understood. Antibiotic usage elevates the risk of contracting gastroenteritis caused by Salmonella enterica serovars, increases the duration for which patients shed the pathogen in their faeces, and may on occasion produce a bacteriologic and symptomatic relapse. These antibiotic-induced changes in the gut microbiota can be studied in mice, in which the disruption of a balanced microbial community by treatment with the antibiotic streptomycin leads to an expansion of S. enterica serovars in the large bowel. However, the mechanisms by which streptomycin treatment drives an expansion of S. enterica serovars are not fully resolved. Here we show that host-mediated oxidation of galactose and glucose promotes post-antibiotic expansion of S. enterica serovar Typhimurium (S. Typhimurium). By elevating expression of the gene encoding inducible nitric oxide synthase (iNOS) in the caecal mucosa, streptomycin treatment increased post-antibiotic availability of the oxidation products galactarate and glucarate in the murine caecum. S. Typhimurium used galactarate and glucarate within the gut lumen of streptomycin pre-treated mice, and genetic ablation of the respective catabolic pathways reduced S. Typhimurium competitiveness. Our results identify host-mediated oxidation of carbohydrates in the gut as a mechanism for post-antibiotic pathogen expansion.
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