The Human Microbiome, an Emerging Key-Player in the Sex Gap in Respiratory Diseases

Abstract

The sex gap is well-documented in respiratory diseases such as cystic fibrosis and chronic obstructive pulmonary disease. While the differences between males and females in prevalence, severity and prognosis are well-established, the pathophysiology of the sex difference has been poorly characterized to date. Over the past 10 years, metagenomics-based studies have revealed the presence of a resident microbiome in the respiratory tract and its central role in respiratory disease. The lung microbiome is associated with host immune response and health outcomes in both animal models and patient cohorts. The study of the lung microbiome is therefore an interesting new avenue to explore in order to understand the sex gap observed in respiratory diseases. Another important parameter to consider is the gut-lung axis, since the gut microbiome plays a crucial role in distant immune modulation in respiratory diseases, and an intestinal “microgenderome” has been reported: i.e., sexual dimorphism in the gut microbiome. The microgenderome provides new pathophysiological clues, as it defines the interactions between microbiome, sex hormones, immunity and disease susceptibility. As research on the microbiome is increasing in volume and scope, the objective of this review was to describe the state-of-the-art on the sex gap in respiratory medicine (acute pulmonary infection and chronic lung disease) in the light of the microbiome, including evidence of local (lung) or distant (gut) contributions to the pathophysiology of these diseases.

Multidrug-Resistant Bacteria in Children and Adolescents with Cystic Fibrosis

“…Nevertheless, female sex in CF was shown to be a significant risk factor for death; women also acquire P. aeruginosa at an earlier age, as well as several other pathogens such as S. aureus , Haemophilus influenzae , A. xyloxidans , B. cepacia , Aspergillus and nontuberculous mycobacteria [ 20 ]. A wide range of factors have been examined to explain the sex gap in airway diseases [ 21 ]. In a study investigating the impact of inhaled aztreonam on the lung microbiome in CF, males showed a significantly higher Shannon diversity index with lower abundance of P. aeruginosa and increased abundance in other genera, including Streptococcus spp.…”

Asthma and Respiratory Infections From Birth to Young Adulthood

“…To our knowledge, this is the first study to have reported a modifying effect of sex on the relationship between asthma and RTIs. The stronger effect of asthma on susceptibility to infections in girls compared with boys in young adulthood could be explained by the differences in airway microbiota ( 36 ), by sex hormones ( 33 ), and/or by different types of immune responses ( 33 ).…”

Differences of the Nasal Microbiome and Mycobiome by Clinical Characteristics of COPD Patients

“…It has been proposed that differences in the composition of the airway microbiome of men and women, determined by host factors such as sex hormones, anatomy, and the immune environment, may explain some of the sex differences in the clinical features of COPD. 56 For example, women tend to develop COPD at an earlier age than men, and tend to have better lung function but more dyspnea and more frequent COPD exacerbations than men. 57,58 So far, little has been reported on sex differences in the lung microbiome in COPD.…”