Azithromycin alters spatial and temporal dynamics of airway microbiota in idiopathic pulmonary fibrosis.

Background: High bacterial burden in the lung microbiota predicts progression of idiopathic pulmonary fibrosis (IPF). Azithromycin (AZT) is a macrolide antibiotic known to alter the lung microbiota in several chronic pulmonary diseases, and observational studies have shown a positive effect of AZT on mortality and hospitalisation rate in IPF. However, the effect of AZT on the lung microbiota in IPF remains unknown. Methods: We sought to determine the impact of a 3-month course of AZT on the lung microbiota in IPF. We assessed sputum and oropharyngeal swab specimens from 24 adults with IPF included in a randomised controlled crossover trial of oral AZT 500 mg 3 times per week. 16S rRNA gene amplicon sequencing and quantitative PCR (qPCR) were performed to assess bacterial communities. Antibiotic resistance genes (ARGs) were assessed using real-time qPCR. Results: AZT significantly decreased community diversity with a stronger and more persistent effect in the lower airways (sputum). AZT treatment altered the temporal kinetics of the upper (oropharyngeal swab) and lower airway microbiota, increasing community similarity between the two sites for 1 month after macrolide cessation. Patients with an increase in ARG carriage had lower bacterial density and enrichment of the genus Streptococcus. In contrast, patients with more stable ARG carriage had higher bacterial density and enrichment in Prevotella. Conclusions: AZT caused sustained changes in the diversity and composition of the upper and lower airway microbiota in IPF, with effects on the temporal and spatial dynamics between the two sites.

A prevalent and culturable microbiota links ecological balance to clinical stability of the human lung after transplantation.

There is accumulating evidence that the lower airway microbiota impacts lung health. However, the link between microbial community composition and lung homeostasis remains elusive. We combine amplicon sequencing and bacterial culturing to characterize the viable bacterial community in 234 longitudinal bronchoalveolar lavage samples from 64 lung transplant recipients and establish links to viral loads, host gene expression, lung function, and transplant health. We find that the lung microbiota post-transplant can be categorized into four distinct compositional states, 'pneumotypes'. The predominant 'balanced' pneumotype is characterized by a diverse bacterial community with moderate viral loads, and host gene expression profiles suggesting immune tolerance. The other three pneumotypes are characterized by being either microbiota-depleted, or dominated by potential pathogens, and are linked to increased immune activity, lower respiratory function, and increased risks of infection and rejection. Collectively, our findings establish a link between the lung microbial ecosystem, human lung function, and clinical stability post-transplant.

Early-Life Formation of the Microbial and Immunological Environment of the Human Airways.

Crosstalk between immune cells and the microbiota in mucosal tissues can set an individual on a trajectory toward health or disease. Little is known about these early-life events in the human respiratory tract. We examined bacterial colonization and immune system maturation in the lower airways over the first year of life. The lower respiratory tract microbiota forms within the first 2 postnatal months. Within the first weeks, three microbial profiles are evident, broadly distinguished as dysbiotic or diverse, and representing different microbial virulence potentials, including proteolysis of immunoglobulin A (IgA) that is critical for mucosal defense. Delivery mode determines microbiota constituents in preterm, but not term, births. Gestational age is a key determinant of immune maturation, with airway cells progressively increasing expression of proallergic cytokine interleukin-33 and genes linked with IgA. These data reveal microbial and immunological development in human airways, and may inform early-life interventions to prevent respiratory diseases.

Cadmium(II) adsorption using functional mesoporous silica and activated carbon.

The role of surface functionality on silica and carbonaceous materials for adsorption of cadmium(II) was examined using various mesoporous silica and activated carbon. Silica surfaces were principally functionalized by mono-amino- and mercapto-groups, while carboxylic group was introduced to the activated carbons by oxidation. Functional groups on silica surface were formed using grafting and co-condensation techniques in their preparation. Mono-amino group was found more effective than di- and tri-amino groups for cadmium(II) adsorption on the grafted silica. Mono-amino groups prepared by co-condensation adsorbed cadmium(II) as much as 0.25mmol/g compared to mercapto- and carboxyl-groups which adsorbed around 0.12mmol/g, whereas Langmuir adsorption affinities were as strong as 50-60L/mmol for all of the three functions. The working pH range was wider for mercapto- and carboxyl-functions than for amino-group. Basic site could be an adsorption center for amino-functional groups while ion exchange sites were found to work for the mercapto- and carboxyl-functions to adsorb cadmium(II) from aqueous phase. Based on the experimental results, surface functional groups rather than structure of silica and carbon seemed to play a decisive role for cadmium(II) adsorption.

Evaluation of mesoporous cyclodextrin-silica nanocomposites for the removal of pesticides from aqueous media.

The treatment of aqueous solutions containing various pesticides by cyclodextrin-functionalized mesoporous silica adsorbents was investigated. The pesticides studied belonged to three chemical structure classes: hexachlorocyclohexane-based, hexachlorobicycloheptene-based, and p,p' substituted biphenyl-based pesticides. The solutions studied contained a mass concentration with respect to each pesticide in the range of 0.060-0.270 microg/mL, values that are consistentwith the low levels typically encountered in environmental samples. Adsorbents containing low to intermediate amounts of cyclodextrin groups were found to have optimal adsorption affinity toward the pesticides. The materials were particularly specific toward p,p'substituted diphenyl-based pesticides such as DDT and DDE.

Phenotypic effects of continuous or discontinuous treatment with dexamethasone and/or calcitriol on osteoblasts differentiated from rat bone marrow stromal cells.

Osteoblasts are target cells for glucocorticoids and calcitriol, and their phenotype is greatly modified by these hormones. We investigated the effect of continuous or discontinuous hormonal exposure to osteoblasts derived from rat bone marrow stromal cells in long-term subcultures. Stromal cells were grown in primoculture in presence of dexamethasone (dex), but in following subcultures, dex and/or calcitriol were added just after seeding or after a 7-day hormone-free period. Cell proliferation, alkaline phosphatase (ALP) histochemical staining, and enzymatic bioactivity measurement, osteocalcin (OC), ALP and bone sialoprotein (BSP) mRNA expression were used to study the differential effect on osteoblastic phenotype of various conditions of treatment by dex and calcitriol. In primoculture, the osteoblastic differentiation was confirmed by the formation of calcified nodules and by strong expression of ALP, OC, and BSP mRNAs. In subcultures, proliferation of stromal cells was stimulated by dex and inhibited by calcitriol and by both hormones. Cell proliferation was not modified by hormonal lack during 7 days. Continuous hormonal treatment by dex strongly enhanced OC and BSP mRNAs, but apparently did not modified ALP mRNAs expression. Continuous treatment by calcitriol decreased ALP and the dex-induced BSP expression and stimulated the OC mRNAs level, strongly when associated with dex. The population of ALP+ cells and ALP bioactivity were strongly increased by dex, whereas calcitriol or both hormones decreased them. When the subcultures were undergone without hormonal treatment during 7 days, all osteogenic mRNAs strongly decreased even after hormonal recovery. Dex, calcitriol, and both hormones inhibited ALP mRNAs. OC messengers were only weakly detectable with both hormones. ALP+ cell population and ALP bioactivity were decreased after 14 days of hormonal treatment recovery. These results support that continuous presence of glucocorticoids appears as a major key for the permanent expression of the osteoblastic phenotype that is inhibited by calcitriol, in the rat bone marrow.