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. 2022 Mar 16:12:863399.
doi: 10.3389/fcimb.2022.863399. eCollection 2022.

Whole Genome Profiling of Lung Microbiome in Solid Organ Transplant Recipients Reveals Virus Involved Microecology May Worsen Prognosis

Lingai Pan  1   2 , Fengsheng Wu  3 , Qingqing Cai  3 , Zhuofei Xu  3 , Huan Hu  2 , Tian Tang  2 , Ruiming Yue  2 , Yifu Hou  4 , Xiaoqin Zhang  2 , Yuan Fang  3 , Xiaobo Huang  2 , Yan Kang  1
Affiliations

Whole Genome Profiling of Lung Microbiome in Solid Organ Transplant Recipients Reveals Virus Involved Microecology May Worsen Prognosis

Lingai Pan et al. Front Cell Infect Microbiol. .

Abstract

Solid organ transplantation (SOT) is the final therapeutic option for recipients with end-stage organ failure, and its long-term success is limited by infections and chronic allograft dysfunction. Viral infection in SOT recipients is considered an important factor affecting prognosis. In this study, we retrospectively analyzed 43 cases of respiratory infections in SOT recipients using metagenomic next-generation sequencing (mNGS) for bronchoalveolar lavage fluid (BALF). At least one virus was detected in 26 (60.5%) recipients, while 17 (39.5%) were virus-negative. Among virus-positive recipients, cytomegalovirus (CMV) was detected in 14 (32.6%), Torque teno virus (TTV) was detected in 9 (20.9%), and other viruses were detected in 6 (14.0%). Prognostic analysis showed that the mortality of the virus-positive group was higher than that of the virus-negative group regardless whether it is the main cause of infection. Analysis of different types of viruses showed that the mortality of the CMV-positive group was significantly higher than that of the CMV-negative group, but no significant difference was observed in other type of virus groups. The diversity analysis of the lung microbiome showed that there was a significant difference between the virus-positive group and the negative group, in particular, the significant differences in microorganisms such as Pneumocystis jirovecii (PJP) and Moraxella osloensiswere detected. Moreover, in the presence of CMV, Pneumocystis jirovecii, Veillonella parvula, and other species showed dramatic changes in the lung of SOT patients, implying that high degree of co-infection between CMV and Pneumocystis jirovecii may occur. Taken together, our study shows that the presence of virus is associated with worse prognosis and dramatically altered lung microbiota in SOT recipients.

Keywords: cytomegalovirus; lung microbiome; mortality; solid organ transplant; virus.

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Conflict of interest statement

Authors FW, QC, ZX, and YF are employed by Genoxor Medical Science and Technology Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Study design in solid organ transplantation.
Figure 2
Figure 2
Diversity and reads counts of viruses identified in this study. CMV, Human betaherpesvirus 5; TTV, Torque teno virus; HSV1, Human alphaherpesvirus 1; EBV, Human gammaherpesvirus 4; BKV, BK virus; B19, Human erythroparvovirus 19; HHV-7, Human betaherpesvirus 7; VZV, Varicella Zoster Virus. The numbers on the histogram represent the sample sizes of the corresponding virus. The numbers in the table represent the reads of mNGS results. S14 and S7 etc, sample number. The samples are sorted according to hierarchical clustering with Euclidean distance.
Figure 3
Figure 3
90-Days Survival proportions of different virus. (A) Survival proportions of virus and non-virus, p = 0.0828; (B) survival proportions of CMV and non-CMV, p = 0.0456; (C) survival proportions of TTV and non-TTV, p = 0.7306. Recipient number is displayed in the Number at risk.
Figure 4
Figure 4
Differences of lung microbiota in groups. (A) Top 20 most abundant species and their relative abundance in virus and non-virus recipients; (B) there were significant differences in top-20 species (such as Pneumocystis jirovecii, Moraxella osloensis, CMV) and other non-top species between virus and non-virus group; (C) top 20 most abundant species and their relative abundance in CMV and non-CMV infectious recipients; (D) there were significant differences in top-20 species (such as Pneumocystis jirovecii, Veillonella parvula) and other non-top species between CMV and non-CMV group.
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