Diffei Academic | mNGS reveals the role of lung microbiota in primary graft dysfunction in lung transplant recipients

Introduction

Recently, the Department of Respiratory and Critical Care Medicine of China-Japan Friendship Hospital cooperated with Diffei Medical to conduct mNGS detection on the bronchoalveolar lavage fluid of 32 patients with lung transplantation and primary graft dysfunction (PGD).To explore the role of lung microbiota in patients with lung transplantation and PGD.Studies have shown that there are changes in the lung flora of patients with PGD grade 3, and the imbalance of lung flora is related to lung immunity.The research results have been published inThe Journal of Clinical and Transplantation Research。

Research Background

Lung transplantation (LT) is the final treatment option for patients with end-stage lung disease, and primary graft dysfunction (PGD) is a common complication after lung transplantation.

PGDIt is a clinical syndrome of acute lung injury that occurs within 72 hours after lung transplantation and is characterized by hypoxemia and alveolar infiltrates on chest radiography.High-grade PGD is associated with worse prognosis after lung transplantation.

Lung microbes play important roles in lung development, immunity, and promoting or inhibiting the development of lung diseases.This study used mNGS technology to explore the association between PGD and patients' lung flora, and evaluate the contribution of microbiota characteristics to patients' early prognosis.

Research result

Severe PGD alters lung microbial composition

11Two patients with PGD grade 3 (PGD 3 group) and 21 patients with PGD grade 0-2 (control group) were included in the study.At the phylum level, the abundance of Actinobacteria, Proteobacteria, Firmicutes, Bacteroidetes and Firmicutes was the highest, while at the species level, Corynebacterium stripes, R. mycosalis, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, etc. are the most common species (Fig. 1A, B).

The abundance of certain bacterial groups in the lungs of the two groups of patients was different at the order, family, and genus levels (Figure 1C-E).

The above analysis shows that the severity of PGD affects the overall composition of the lung microbiota.

Figure 1 Changes in the lung microbiota of PGD patients

PGD ​​3Differences in abundance of specific bacterial taxa among patients

LEfSe was used to compare the relative abundance of important taxa in PGD grade 3 patients and controls, and a total of 16 groups of bacteria were detected with significant differences in abundance (Fig. 2A).

At the genus level, the genera Modestobacter, Scardovia, and Crescentomonas were enriched in PGD grade 3 patients, while the genera Klebsiella and Orostobacter were enriched in controls.

At the species level, Modestobacter marinus and Scardovia wiggsiae were enriched in PGD grade 3 patients, whereas Sinobacter sinus and Streptococcus infantis were enriched in control patients.The cladogram showed that the orders Geodermatophilales and Selenomonadales, the families Geodermatophilaceae and the family Selenomonadaceae were enriched in PGD grade 3 patients, whereas the order Enterobacterales, the family Enterobacteriaceae and the family Lachnospiraceae were enriched in the controls (Fig. 2B)

Figure 2 Species with significant differences in abundance between PGD 3 and the control group

PGD ​​3Alpha diversity in grade 1 patients is associated with altered lung immune function

To explore the relationship between lung microbiota and lung immunity, we detected IL-6, IFN-γ, TNF-α, IL-2, IL-1β, and IL-13 in the bronchoalveolar lavage fluid of all patients. , IL-4, IL-8, IL-10 and IL-12 (p70), including 10 common human cytokines.Spearman correlation analysis was used to find that IL-2 was negatively correlated with bacterial alpha diversity (Shannon and Simpson) in the PGD 3 group (Fig. 3A,B).

The dominant microbiota in lung transplant patients in the early postoperative period (overall cohort) was associated with different levels of alveolar cytokines.Acinetobacter baumannii was significantly positively correlated with IFN-γ, IL-2, IL-13 and IL-12, Staphylococcus aureus was positively correlated with IFN-γ and IL-2, Stenotrophomonas maltophilia was positively correlated with IL- 10 was negatively correlated, Pseudomonas aeruginosa was negatively correlated with IL-1β, and Actinomyces cariosa was negatively correlated with IL-2 (Fig. 3C).

Figure 3 Alpha diversity of lung flora in PGD grade 3 patients is associated with increased lung inflammation

Lung microbiota diversity predicts early survival in lung transplant recipients

Within the entire cohort (n = 32), subjects were divided into three groups based on individual Shannon diversity index percentiles.8 (25%) patients had low diversity (index <0.83), 16 (50%) patients had moderate diversity (0.83 < index <2.37), and 8 (25%) patients had high microbial diversity (index >2.37).

The Kaplan-Meier estimation method was then used to analyze the 30-day overall survival rate of each group of patients.The survival rate of the high- and medium-diversity groups was 100%, and the survival rate of the low-diversity group was 75% (p = 0.041).In the PGD 3 group, there was no significant difference in bacterial diversity between survivors and non-survivors, but the alpha diversity of non-survivors was significantly lower than that of survivors (0.37 ± 0.46 vs 1.53 ± 1.06, p > 0.05).

in conclusion

This study found a relationship between changes in lung flora, alveolar inflammation and PGD, and the diversity of lung flora may predict the early survival rate of lung transplant recipients.

The lung microbiota has potential in the diagnosis and treatment of patients with PGD grade 3, and our results support studies to evaluate the prognostic and diagnostic potential of the lung microbiota and its immune interactions in larger cohorts.

references:

Wu Y, Huang L, Li M, Cui X, Zhan Q, Wang C. The role of lun-g microbiota in primary graft dysfunction in lung transplant recipients. Clin Transplant. 2023 Dec;37(12):e15152. doi: 10.1111 /ctr.15152. Epub 2023 Oct 3. PMID: 37788167.

Compiler: Lily Reviewer: Jia, Aoki Typesetting: Lin