From bench to bedside: lung transplant and probiotics: airway microbiome may affect long-term outcome
A frequent complication of lung transplant is chronic lung allograft dysfunction (CLAD), an umbrella term used to describe different phenotypes of chronic lung allograft rejection characterized by inflammation and aberrant airway and/or parenchyma remodeling that progressively impairs lung function, ultimately leading to retransplantation or death.
A rich and balanced airway microbiota has been linked with the maintenance of local tissue homeostasis. Perturbation in the composition of this microbial community, known as dysbiosis, has been reported in a variety of respiratory conditions, including lung transplantation. The authors of this paper published on JACI suggest that dysbiosis is linked to either inflammation or remodeling, depending on the predominant phylum, and that pulmonary microbiota may impact long-term graft survival. In this study microbiota DNA and host total RNA were isolated from bronchoalveolar lavages (BAL) obtained from patients post lung transplantation and real-time quantitative PCR allowed to quantify the expression of a restricted set of genes encoding for anabolic or catabolic remodeling. The authors showed that after transplantation in BAL four conditions could be described: low, intermediate, catabolic and anabolic. The first two express neutral genes profiles (i.e. genes not associated to remodeling) and are characterized by balanced bacterial communities. The catabolic condition, that more often occurs in the first phase after transplant (3-6 months) is dominated by neutrophil infection, matrix degradation and predominance of proinflammatory bacteria (Staphylococcus and Pseudomonas) associated with inflammatory gene expression profiles. In the anabolic condition, which instead usually happens from 12 months onward, prevail growth factors, matrix deposition and low stimulatory (Prevotella and Streptococcus) bacteria with tissue remodeling gene expression profiles. The authors propose that in the healthy state, the lower airway are characterized by a low-grade matrix turnover and a balanced microbiota while in respiratory diseases associated with acute inflammation or fibrogenesis, lung microenvironment change to catabolic or anabolic remodeling conditions promoting the growth of specific bacteria, which in turn differentially impact matrix regulation.
This paper demonstrates that a key determinant of the lower airway microenvironment may be the interplay among host cells, microbes and the matrix. Furthermore, the authors propose potential new therapeutic opportunities in terms of changing airway microbiota to ultimately improve long-term lung transplant outcome.
Mouraux S, Bernasconi E, Pattaroni C, Koutsokera A, Aubert JD, Claustre J, Pison C, Royer PJ, Magnan A, Kessler R, Benden C, Soccal PM, Marsland BJ, Nicod LP; SysCLAD Consortium. Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung. J Allergy Clin Immunol. 2018 Feb;141(2):718-729.e7