Department of Electrical Engineering and Computer Science, University of Kansas, Lawrence, KS, USA.
Department of Surgery, University of Kansas Medical Center, Kansas City, KS, USA.
BMC Microbiol. 2024 Nov 6;24(1):452. doi: 10.1186/s12866-024-03598-6.
Pathogenic Escherichia coli strains produce neonatal septicemia after colonizing the neonatal gut. While the probiotic Lactobacillus rhamnosus GG (LGG) effectively reduces neonatal sepsis, LGG's effects on the neonatal intestinal microbiota alterations and inflammation triggered by E. coli are incompletely understood. We hypothesized that LGG significantly modulates the specific neonatal gut microbial populations changes and the inflammatory response elicited by the enteral introduction of septicemia-producing E. coli. To test this hypothesis, newborn rats were pretreated orally with LGG or placebo prior to infection with the neonatal E. coli septicemia clinical isolate SCB34. Amplicon 16S rRNA gene sequencing was performed on intestinal samples. Intestinal injury and expression of inflammatory mediators and apoptosis were determined.
Alpha diversity of gut microbiota was greater in SCB34-infected pups in comparison to sham-infected pups, these changes were not modified by LGG pretreatment. Beta diversity analyses also showed differences between SCB34-infected vs. uninfected pups. LGG pretreatment before SCB34 infection did not result in significant beta diversity changes compared to placebo. Moreover, individual genera and species abundance analyses by linear discriminant analysis effect size (LEfSe) showed significant changes in Gram-negative, Gram-positive, and anaerobic populations resulting from LGG pretreatment and SCB34 infection. LGG significantly suppressed the expression of inflammatory cytokines but did not attenuate SCB34-induced apoptosis or histologic injury.
LGG modulates clinically significant microbiota features and inflammation triggered by pathogenic E. coli intestinal infection shortly after birth. This new knowledge can potentially be harnessed to design novel interventions against gut-derived neonatal sepsis.
致病性大肠杆菌菌株在定植新生儿肠道后会引发新生儿败血症。虽然益生菌鼠李糖乳杆菌 GG（LGG）能有效降低新生儿败血症的发病率，但 LGG 对大肠杆菌引起的新生儿肠道微生物群改变和炎症的影响尚不完全清楚。我们假设 LGG 能显著调节特定的新生儿肠道微生物群变化和由产败血症大肠杆菌肠内引入引起的炎症反应。为了验证这一假设，我们在新生大鼠感染新生儿大肠杆菌败血症临床分离株 SCB34 之前，用 LGG 或安慰剂进行口服预处理。对肠道样本进行扩增子 16S rRNA 基因测序。测定肠道损伤和炎症介质及凋亡的表达。
与假感染组相比，SCB34 感染组大鼠肠道微生物群的 alpha 多样性更大，而 LGG 预处理并不能改变这些变化。β多样性分析也显示了 SCB34 感染组与未感染组之间的差异。与安慰剂相比，LGG 预处理在 SCB34 感染前并没有导致显著的β多样性变化。此外，通过线性判别分析效应量（LEfSe）对革兰氏阴性菌、革兰氏阳性菌和厌氧菌进行个体属和种丰度分析，结果表明 LGG 预处理和 SCB34 感染导致肠道菌群发生了显著变化。LGG 显著抑制了炎症细胞因子的表达，但不能减轻 SCB34 诱导的凋亡或组织损伤。
LGG 调节了由致病性大肠杆菌肠道感染引发的具有临床意义的微生物群特征和炎症。这一新知识可以为设计针对肠道来源的新生儿败血症的新干预措施提供依据。
