Cystic fibrosis (CF) is a genetic disease with mutational changes leading to profound dysbiosis, both pulmonary and intestinal, from a very young age. This dysbiosis plays an important role in ...clinical manifestations, particularly in the lungs, affected by chronic infection. The range of microbiological tools has recently been enriched by metagenomics based on next-generation sequencing (NGS). Currently applied essentially in a gene-targeted manner, metagenomics has enabled very exhaustive description of bacterial communities in the CF lung niche and, to a lesser extent, the fungi. Aided by progress in bioinformatics, this now makes it possible to envisage shotgun sequencing and opens the door to other areas of the microbial world, the virome, and the archaeome, for which almost everything remains to be described in cystic fibrosis. Paradoxically, applying NGS in microbiology has seen a rebirth of bacterial culture, but in an extended manner (culturomics), which has proved to be a perfectly complementary approach to NGS. Animal models have also proved indispensable for validating microbiome pathophysiological hypotheses. Description of pathological microbiomes and correlation with clinical status and therapeutics (antibiotic therapy, cystic fibrosis transmembrane conductance regulator (CFTR) modulators) revealed the richness of microbiome data, enabling description of predictive and follow-up biomarkers. Although monogenic, CF is a multifactorial disease, and both genotype and microbiome profiles are crucial interconnected factors in disease progression. Microbiome-genome interactions are thus important to decipher.
Strict anaerobes are undeniably important residents of the cystic fibrosis (CF) lung but are still unknowns. The main objectives of this study were to describe anaerobic bacteria diversity in CF ...airway microbiota and to evaluate the association with lung function. An observational study was conducted during eight months. A hundred and one patients were enrolled in the study, and 150 sputum samples were collected using a sterile sample kit designed to preserve anaerobic conditions. An extended-culture approach on 112 sputa and a molecular approach (quantitative PCR targeting three of the main anaerobic genera in CF lung: Prevotella, Veillonella, and Fusobacterium) on 141 sputa were developed. On culture, 91.1% of sputa were positive for at least one anaerobic bacterial species, with an average of six anaerobic species detected per sputum. Thirty-one anaerobic genera and 69 species were found, which is the largest anaerobe diversity ever reported in CF lungs. Better lung function (defined as Forced Expiratory Volume in one second > 70%) was significantly associated with higher quantification of Veillonella. These results raise the question of the potential impact of anaerobes on lung function.
Many scientific papers reported that an unbalanced gut microbiota could lead to or worsen neurodevelopmental disorders (NDD). A dysbiosis may then be observed in the course of development and mark a ...dysfunction within what is called the gut-brain axis. The aim of this systematic review is to investigate potential evidence of dysbiosis in children and young adults with NDD compared to controls. Using the PRISMA guidelines we systematically reviewed studies that compared the gut microbiota in NDD participants (with an age inferior to thirty) to the gut microbiota of controls, regardless of the data analysis methods used. The MEDLINE, Scopus and PsycINFO databases were searched up to September 2018. 31 studies with a total sample size of 3002 ASD (Autism Spectrum Disorder) and 84 ADHD (Attention Deficit Hyperactivity Disorder) participants were included in this systematic review. Independent data extraction and quality assessment were conducted. The quality of the studies was rated from low to high. Population characterization and experimental methods were highly heterogeneous in terms of the data available, selection of criteria, and dysbiosis measurement. A dysbiosis was reported in 28 studies in terms of either diversity, bacterial composition or metabolome dysfunction. Due to heterogeneity, a quantitative synthesis was not applicable. In this paper, we discuss the different biases to understand the complexity of microbiota and neurodevelopmental disorders to provide leads for future cohort studies looking to answer the questions raised by the trillions of microorganisms that inhabit key body niches.
Variations in proteins related to bacterial diversity may affect species identification performed using matrix-assisted laser desorption ionization (MALDI)-time of flight mass spectrometry. Using ...this method, we identified 110 Streptococcus agalactiae isolates characterized by serotyping and multilocus sequence typing. Serotype III and sequence type 23 strains expressed the widest variation in molecular weight of putative "species-identifying" biomarker ions. Recognition of the diversity of MALDI patterns observed in strains that represent all major intraspecies lineages assists in the constitution of an optimal reference database.
Airway microbiota composition has been clearly correlated with many pulmonary diseases, and notably with cystic fibrosis (CF), an autosomal genetic disorder caused by mutation in the CF transmembrane ...conductance regulator (CFTR). Recently, a new molecule, ivacaftor, has been shown to re-establish the functionality of the G551D-mutated CFTR, allowing significant improvement in lung function.
The purpose of this study was to follow the evolution of the airway microbiota in CF patients treated with ivacaftor, using quantitative PCR and pyrosequencing of 16S rRNA amplicons, in order to identify quantitative and qualitative changes in bacterial communities. Three G551D children were followed up longitudinally over a mean period of more than one year covering several months before and after initiation of ivacaftor treatment.
129 operational taxonomy units (OTUs), representing 64 genera, were identified. There was no significant difference in total bacterial load before and after treatment. Comparison of global community composition found no significant changes in microbiota. Two OTUs, however, showed contrasting dynamics: after initiation of ivacaftor, the relative abundance of the anaerobe Porphyromonas 1 increased (p<0.01) and that of Streptococcus 1 (S. mitis group) decreased (p<0.05), possibly in relation to the anti-Gram-positive properties of ivacaftor. The anaerobe Prevotella 2 correlated positively with the pulmonary function test FEV-1 (r=0.73, p<0.05). The study confirmed the presumed positive role of anaerobes in lung function.
Several airway microbiota components, notably anaerobes (obligate or facultative anaerobes), could be valuable biomarkers of lung function improvement under ivacaftor, and could shed light on the pathophysiology of lung disease in CF patients.
It has been hypothesized that gut and oral dysbiosis may contribute to the development of primary Sjögren's syndrome (pSS). The aim of this systematic review was to assemble available data regarding ...the oral and gut microbiota in pSS and to compare them to data from healthy individuals and patients with dry symptoms without a diagnosis of Sjögren's syndrome or lupus disease to identify dysbiosis and discuss the results.
Using the PRISMA guidelines, we systematically reviewed studies that compared the oral and gut microbiota of Sjögren's patients and controls. The PubMed database and Google Scholar were searched.
Two-hundred and eighty-nine studies were found, and 18 studies were included: 13 referred to the oral microbiota, 4 referred to the gut microbiota, and 1 referred to both anatomical sites. The most frequent controls were healthy volunteers and patients with sicca symptoms. The most common analysis method used was 16S-targeted metagenomics. The results were mostly heterogeneous, and the results regarding diversity were not always in accordance. Dysbiosis in pSS was not confirmed, and reduced salivary secretion seems to explain more microbial changes than the underlying disease.
These heterogeneous results might be explained by the lack of a standardized methodology at each step of the process and highlight the need for guidelines. Our review provides evidence that sicca patients seem to be more relevant than healthy subjects as a control group.
Increasing resistance to antibiotics of Pseudomonas aeruginosa leads to therapeutic deadlock and alternative therapies are needed. We aimed to evaluate the effects of Lactobacillus clinical isolates ...in vivo, through intranasal administration on a murine model of Pseudomonas aeruginosa pneumonia. We screened in vitro 50 pulmonary clinical isolates of Lactobacillus for their ability to decrease the synthesis of two QS dependent-virulence factors (elastase and pyocyanin) produced by Pseudomonas aeruginosa strain PAO1. These results demonstrate that intranasal priming with lactobacilli acts as a prophylaxis, and avoids fatal complications caused by Pseudomonas aeruginosa pneumonia in mice. These results were independent of in vitro anti-Pseudomonas aeruginosa activity on QS-dependent virulence factors. Further experiments are required to identify the immune mechanism before initiating clinical trials.
Mycobacterium abscessus, as a species, has been increasingly implicated in respiratory infections, notably in cystic fibrosis patients. The species comprises 3 subspecies, which can be difficult to ...identify. Since they differ in antibiotic susceptibility and clinical relevance, developing a routine diagnostic tool discriminating Mycobacterium abscessus at the subspecies level is a real challenge. Forty-three Mycobacterium abscessus species isolates, previously identified by multilocus sequence typing, were analyzed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). A subspecies identification algorithm, based on five discriminating peaks, was drawn up and validated by blind identification of a further 49 strains, 94% of which (n = 46) were correctly identified. Two M. abscessus subsp. massiliense strains were misidentified as M. abscessus subsp. abscessus, and for 1 other strain identification failed. Inter- and intralaboratory reproducibility tests were conclusive. This study presents, for the first time, a classification algorithm for MALDI-TOF MS identification of the 3 M. abscessus subspecies. MALDI-TOF MS proved effective in discriminating within the M. abscessus species and might be easily integrated into the workflow of microbiology labs.
Anaerobes form a large part of microbial communities, and have begun to be specifically studied in both healthy and pathologic contexts. Porphyromonas is one of the top ten anaerobic taxa in the ...microbiome (anaerobiome) in healthy subjects. However, to date, most studies focused on the deleterious role of P. gingivalis, the most widely described species. Interestingly, targeted metagenomics reveals Porphyromonas other than gingivalis (POTG), highlighting other species such as P. catoniae or P. pasteri as potential biomarkers in disease progression or pathogen colonization susceptibility. From the sparse data, it appears that the Porphyromonas genus may also be a relevant target of investigation in several pulmonary diseases. Moreover, deciphering cutaneous, gastric and oral microbiomes hint that Porphyromonas may be a genus of interest in non-pulmonary diseases.
This review aims to summarize the major data on POTG and to report their impact on the various human microbiomes in different clinical states.
•Porphyromonas is a bacterial genus that belongs to the respiratory core microbiome.•Important species in the pulmonary niche are Porphyromonas other than P. gingivalis (POTG).•POTG are understated and little studied.•The abundance of POTG is decreased whatever the respiratory disease.•POTG are also an interesting target of investigation in non-pulmonary microbiomes, particularly gastric, oral and cutaneous.