抗结核药物可能引起肠道菌群失调,而损伤对结核分枝杆菌的免疫力

创作:女巫 审核:沈志勋 03月12日
使用抗结核药物利福平(RIF)或异烟肼(INH)和吡嗪酰胺(PYZ)治疗小鼠,显著改变了肠道菌群的组成;
在结核分枝杆菌(Mtb)感染之前用抗结核药物INH和PYZ(而不是RIF)处理小鼠,导致Mtb的负荷增加,该效应可通过移植未处理动物的粪菌逆转;
机制上,INH/PYZ处理小鼠对Mtb感染的易感性增加与肺泡巨噬细胞的代谢受损和杀菌活性缺陷相关;
广泛使用的抗结核治疗(ATT)诱导的肠道失调,可能对肺泡巨噬细胞的抗Mtb反应产生不利影响。
延伸阅读
Mucosal Immunology [IF:7.352]

Intestinal dysbiosis compromises alveolar macrophage immunity to Mycobacterium tuberculosis

肠道菌群失调损害肺泡巨噬细胞对结核分枝杆菌的免疫力

02-19, Article, 10.1038/s41385-019-0147-3more

Abstract:
Current treatments for tuberculosis (TB) are effective in controlling Mycobacterium tuberculosis (Mtb) growth, yet have significant side effects and do not prevent reinfection. Therefore, it is critical to understand why our host defense system is unable to generate permanent immunity to Mtb despite prolonged anti-tuberculosis therapy (ATT). Here, we demonstrate that treatment of mice with the most widely used anti-TB drugs, rifampicin (RIF) or isoniazid (INH) and pyrazinamide (PYZ), significantly altered the composition of the gut microbiota. Unexpectedly, treatment of mice with the pro-Mtb drugs INH and PYZ, but not RIF, prior to Mtb infection resulted in an increased bacterial burden, an effect that was reversible by fecal transplantation from untreated animals. Mechanistically, susceptibility of INH/PYZ-treated mice was associated with impaired metabolism of alveolar macrophages and defective bactericidal activity. Collectively, these data indicate that dysbiosis induced by ATT administered to millions of individuals worldwide may have adverse effects on the anti-Mtb response of alveolar macrophages.

First Authors:
Nargis Khan

Correspondence Authors:
Maziar Divangahi,Irah L King

All Authors:
Nargis Khan,Laura Mendonca,Achal Dhariwal,Ghislaine Fontes,Dick Menzies,Jianguo Xia,Maziar Divangahi,Irah L King