Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
Michael Smith Laboratories, University of British Columbia, Vancouver, Canada.
Elife. 2021 Apr 20;10:e67740. doi: 10.7554/eLife.67740.
Bacterial members of the infant gut microbiota and bacterial-derived short-chain fatty acids (SCFAs) have been shown to be protective against childhood asthma, but a role for the fungal microbiota in asthma etiology remains poorly defined. We recently reported an association between overgrowth of the yeast in the gut microbiota of Ecuadorian infants and increased asthma risk. In the present study, we replicated these findings in Canadian infants and investigated a causal association between early life gut fungal dysbiosis and later allergic airway disease (AAD). In a mouse model, we demonstrate that overgrowth of within the neonatal gut exacerbates features of type-2 and -17 inflammation during AAD later in life. We further show that growth and adherence to gut epithelial cells are altered by SCFAs. Collectively, our results underscore the potential for leveraging inter-kingdom interactions when designing putative microbiota-based asthma therapeutics.
婴儿肠道微生物群中的细菌成员和细菌衍生的短链脂肪酸 (SCFA) 已被证明可预防儿童哮喘,但真菌微生物群在哮喘发病机制中的作用仍未得到明确界定。我们最近报道了肠道微生物群中酵母过度生长与增加的哮喘风险之间的关联。在本研究中,我们在加拿大婴儿中复制了这些发现,并研究了生命早期肠道真菌失调与后期过敏性气道疾病 (AAD) 之间的因果关联。在小鼠模型中,我们证明了新生肠道中酵母的过度生长会加剧生命后期 AAD 时 2 型和 17 型炎症的特征。我们还表明,SCFA 改变了肠道上皮细胞对的生长和粘附。总的来说,我们的结果强调了在设计基于微生物组的哮喘治疗方法时利用跨王国相互作用的潜力。