ABSTRACT

While the intestinal microbiome seems a major driver of persistent immune defects in people with HIV (PWH), little is known about its fungal component, the mycobiome. We assessed the inter-kingdom mycobiome–bacteriome interactions, the impact of diet, and the association with the innate and adaptive immunity in PWH on antiretroviral therapy. We included 24 PWH individuals and 12 healthy controls. We sequenced the Internal Transcribed Spacer 2 amplicons, determined amplicon sequence variants, measured biomarkers of the innate and adaptive immunity in blood and relations with diet. Compared to healthy controls, PWH subjects exhibited a distinct and richer mycobiome and an enrichment for Debaryomyces hansenii, Candida albicans, and Candida parapsilosis. In PWH, Candida and Pichia species were strongly correlated with several bacterial genera, including Faecalibacterium genus. Regarding the links between the mycobiome and systemic immunology, we found a positive correlation between Candida species and the levels of proinflammatory cytokines (sTNF-R2 and IL-17), interleukin 22 (a cytokine implicated in the regulation of mucosal immunity), and CD8+ T cell counts. This suggests an important role of the yeasts in systemic innate and adaptive immune responses. Finally, we identified inter-kingdom interactions implicated in fiber degradation, short-chain fatty acid production, and lipid metabolism, and an effect of vegetable and fiber intake on the mycobiome. Therefore, despite the great differences in abundance and diversity between the bacterial and fungal communities of the gut, we defined the changes associated with HIV, determined several different inter-kingdom associations, and found links between the mycobiome, nutrient metabolism, and systemic immunity.

摘要

虽然肠道微生物组似乎是 HIV 感染者 (PWH) 持续免疫缺陷的主要驱动因素，但人们对其真菌成分——真菌生物组知之甚少。我们评估了王国间的微生物组-细菌组相互作用、饮食的影响，以及 PWH 中先天性和适应性免疫与抗逆转录病毒治疗的关系。我们纳入了 24 名 PWH 个体和 12 名健康对照。我们对内部转录间隔 2 扩增子进行了测序，确定了扩增子序列变体，测量了血液中先天性和适应性免疫的生物标志物以及与饮食的关系。与健康对照组相比，PWH 受试者表现出独特和丰富的菌群，并富集了汉森德巴利菌、白色念珠菌和近平滑念珠菌。在 PWH 中，念珠菌毕赤酵母属与包括粪杆菌属在内的几个细菌属密切相关。关于菌群和全身免疫学之间的联系，我们发现念珠菌之间呈正相关物种和促炎细胞因子（sTNF-R2 和 IL-17）、白细胞介素 22（一种参与黏膜免疫调节的细胞因子）和 CD8+ T 细胞计数的水平。这表明酵母在系统性先天性和适应性免疫反应中的重要作用。最后，我们确定了与纤维降解、短链脂肪酸产生和脂质代谢有关的王国间相互作用，以及蔬菜和纤维摄入对菌群的影响。因此，尽管肠道细菌和真菌群落的丰度和多样性存在很大差异，但我们确定了与 HIV 相关的变化，确定了几种不同的界际关联，并发现了真菌群、营养代谢和全身免疫之间的联系。