Research press release


Nature Medicine

Gut microbes promote host defense



Hitesh Deshmukh、G Scott Worthenたちは、臨床的に重要な3種類または5種類の抗生物質を組み合わせ、子宮内で、また誕生後に新生仔マウスに長期間これを投与すると、大腸菌E. coliK1株と肺炎桿菌の感染によって生じた敗血症に対する防御作用が弱まることを発見した。通常は、誕生後間もない時期に、腸内微生物が好中球(免疫細胞の一種で、大腸菌感染の制御に重要な役割を担う)の発生と血流中への移行を誘発する。周産期に抗生物質に曝露すると、この好中球数の初期の増加が抑制される。抗生物質投与したマウスに微生物を移植すると、循環血中と骨髄の好中球が増加し、大腸菌感染による敗血症に対する防御が回復する。

The early colonization of the neonatal mouse gut by microbes is associated with protection from systemic bacterial infection later in life, according to a study published this week in Nature Medicine. These findings suggest that exposure to antibiotics near the time of birth can alter immune cell development and impair host defense to infections.

Commensal microbes in the gut provide signals that promote immune cell development. Previous studies have found that prolonged exposure of neonates to antibiotics perturbs colonization by microbes and is associated with increased risk of late-onset sepsis.

Hitesh Deshmukh, G Scott Worthen and colleagues found that prolonged exposure of neonatal mice to a clinically-relevant combination of three or five antibiotics in utero and after birth impaired their defense against sepsis caused by Escherichia coli (E. coli) K1 and Klebsiella pneumoniae infections. Shortly after birth, gut microbes normally induce the development and mobilization into the bloodstream of neutrophils, an immune cell type important for controlling E. coli infection. Perinatal antibiotic exposure reduces this early rise in neutrophil numbers. Transfer of microbes into antibiotic-treated mice increases neutrophil numbers in the circulation and bone marrow, restoring protection from sepsis caused by E. coli.

doi: 10.1038/nm.3542


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