Rowett Institute, University of Aberdeen, Aberdeen, AB25 2ZD, United Kingdom.
CIBIO - Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, 38123, Italy.
FEMS Microbiol Ecol. 2022 Sep 19;98(10). doi: 10.1093/femsec/fiac095.
The human gut microbiota protects the host from invading pathogens and the overgrowth of indigenous opportunistic species via a process called colonization resistance. Here, we investigated the antagonistic activity of human gut bacteria towards Candida albicans, an opportunistic fungal pathogen that can cause severe infections in susceptible individuals. Coculture batch incubations of C. albicans in the presence of faecal microbiota from six healthy individuals revealed varying levels of inhibitory activity against C. albicans. 16S rRNA gene amplicon profiling of these faecal coculture bacterial communities showed that the Bifidobacteriaceae family, and Bifidobacterium adolescentis in particular, were most correlated with antagonistic activity against C. albicans. Follow-up mechanistic studies performed under anaerobic conditions confirmed that culture supernatants of Bifidobacterium species, particularly B. adolescentis, inhibited C. albicans in vitro. Fermentation acids (FA), including acetate and lactate, present in the bifidobacterial supernatants were important contributors to inhibitory activity. However, increasing the pH of both bacterial supernatants and mixtures of FA reduced their anti-Candida effects, indicating a combinatorial effect of prevailing pH and FA. This work, therefore, demonstrates potential mechanisms underpinning gut microbiome-mediated colonization resistance against C. albicans, and identifies particularly inhibitory components such as bifidobacteria and FA as targets for further study.
人类肠道微生物群通过一种称为定植抵抗的过程保护宿主免受入侵病原体和本土机会性病原体的过度生长。在这里，我们研究了人类肠道细菌对白色念珠菌（一种机会性真菌病原体，可导致易感个体发生严重感染）的拮抗活性。在存在来自 6 个健康个体的粪便微生物群的条件下进行的白色念珠菌共培养批量孵育显示出对白色念珠菌的抑制活性存在不同程度的差异。对这些粪便共培养细菌群落的 16S rRNA 基因扩增子分析表明，双歧杆菌科，特别是青春双歧杆菌，与抗白色念珠菌活性最相关。在厌氧条件下进行的后续机制研究证实，双歧杆菌属的培养上清液，特别是青春双歧杆菌，在体外抑制白色念珠菌。发酵酸（FA），包括乙酸和乳酸，存在于双歧杆菌上清液中，是抑制活性的重要贡献者。然而，增加细菌上清液和 FA 混合物的 pH 值会降低其抗念珠菌作用，表明存在 pH 值和 FA 的组合效应。因此，这项工作证明了肠道微生物组介导的对白色念珠菌定植抵抗的潜在机制，并确定了双歧杆菌和 FA 等特别抑制性成分作为进一步研究的目标。
