Damian W. Rivett

A novel microbiota stratification system predicts future exacerbations in bronchiectasis.

RATIONALE Although airway microbiota composition correlates with clinical measures in non-cystic fibrosis bronchiectasis, these data are unlikely to provide useful prognostic information at the individual patient level. A system enabling microbiota data to be applied clinically would represent a substantial translational advance. OBJECTIVES This study aims to determine whether stratification of patients according to the predominant microbiota taxon can provide improved clinical insight compared with standard diagnostics. METHODS The presence of bacterial respiratory pathogens was assessed in induced sputum from 107 adult patients by culture, quantitative PCR, and, in 96 samples, by ribosomal gene pyrosequencing. Prospective analysis was performed on samples from 42 of these patients. Microbiological data were correlated with concurrent clinical measures and subsequent outcomes. MEASUREMENTS AND MAIN RESULTS Microbiota analysis defined three groups: Pseudomonas aeruginosa dominated (n = 26), Haemophilus influenzae dominated (n = 34), and other taxa dominated (n = 36). Patients with P. aeruginosa- and H. influenzae-dominated communities had significantly worse lung function, higher serum levels of C-reactive protein (CRP), and higher sputum levels of IL-8 and IL-1β. Predominance of P. aeruginosa, followed by Veillonella species, was the best predictor of future exacerbation frequency, with H. influenzae-dominated communities having significantly fewer episodes. Detection of P. aeruginosa was associated with poor lung function and exacerbation frequency, irrespective of analytical strategy. Quantitative PCR revealed significant correlations between H. influenzae levels and sputum IL-8, IL-1β, and serum CRP. Genus richness was negatively correlated with 24-hour sputum weight, age, serum CRP, sputum IL-1β, and IL-8. CONCLUSIONS Stratification of patients with non-cystic fibrosis bronchiectasis on the basis of predominant bacterial taxa is more clinically informative than either conventional culture or quantitative PCR-based analysis. Further investigation is now required to assess the mechanistic basis of these associations.

Where less may be more: how the rare biosphere pulls ecosystems strings

Rare species are increasingly recognized as crucial, yet vulnerable components of Earth’s ecosystems. This is also true for microbial communities, which are typically composed of a high number of relatively rare species. Recent studies have demonstrated that rare species can have an over-proportional role in biogeochemical cycles and may be a hidden driver of microbiome function. In this review, we provide an ecological overview of the rare microbial biosphere, including causes of rarity and the impacts of rare species on ecosystem functioning. We discuss how rare species can have a preponderant role for local biodiversity and species turnover with rarity potentially bound to phylogenetically conserved features. Rare microbes may therefore be overlooked keystone species regulating the functioning of host-associated, terrestrial and aquatic environments. We conclude this review with recommendations to guide scientists interested in investigating this rapidly emerging research area.

TRPV1 Deletion Enhances Local Inflammation and Accelerates the Onset of Systemic Inflammatory Response Syndrome

The transient receptor potential vanilloid 1 (TRPV1) is primarily localized to sensory nerve fibers and is associated with the stimulation of pain and inflammation. TRPV1 knockout (TRPV1KO) mice show enhanced LPS-induced sepsis compared with wild type (WT). This implies that TRPV1 may have a key modulatory role in increasing the beneficial and reducing the harmful components in sepsis. We investigated immune and inflammatory mechanisms in a cecal ligation and puncture (CLP) model of sepsis over 24 h. CLP TRPV1KO mice exhibited significant hypothermia, hypotension, and organ dysfunction compared with CLP WT mice. Analysis of the inflammatory responses at the site of initial infection (peritoneal cavity) revealed that CLP TRPV1KO mice exhibited: 1) decreased mononuclear cell integrity associated with apoptosis, 2) decreased macrophage tachykinin NK1-dependent phagocytosis, 3) substantially decreased levels of nitrite (indicative of NO) and reactive oxygen species, 4) increased cytokine levels, and 5) decreased bacteria clearance when compared with CLP WT mice. Therefore, TRPV1 deletion is associated with impaired macrophage-associated defense mechanisms. Thus, TRPV1 acts to protect against the damaging impact of sepsis and may influence the transition from local to a systemic inflammatory state.

Is there an association between microbial exposure and food allergy? A systematic review

The environmental factors driving the recent increase in the prevalence of food allergy (FA) are unclear. Since associations have been demonstrated between microbial exposure and the likelihood of eczema and respiratory allergies, we reviewed the evidence for FA. Medline was systematically searched from inception to the end of July 2012 for studies investigating links between FA and environmental exposures, likely to influence microbial exposure, such as Caesarean delivery, family size, day‐care attendance, childhood infections, immunizations and antibiotic use. We selected studies reporting food challenge data, reported doctor‐diagnosed (RDD) FA and food sensitization. Methodological differences and study heterogeneity precluded meta‐analysis. A total of 46 studies were identified, of which 28 (60.9%) were prospective and 13 (28.3%) used food challenges to diagnose FA. Caesarean delivery was investigated in 13 studies, of which three infant cohorts demonstrated an increase in challenge‐proven FA (one cohort) and food sensitization (two cohorts), and one cross‐sectional study reported increased RDDFA. Four studies investigated the effect of having siblings, with one infant cohort demonstrating less challenge‐proven FA and a cross‐sectional study showing a decrease in RDDFA. Attending childcare before 6 months was associated with less challenge‐proven FA in one cohort. A cross‐sectional survey identified an inverse relationship between hepatitis A serology and peanut sensitization. One of eleven trials investigating probiotics demonstrated a quicker acquisition of milk tolerance amongst allergic infants. Factors influencing microbial exposure may be partly responsible for rising FA burden, but further prospective studies using double‐blind placebo controlled food challenges as an outcome are required.

The impact of azithromycin therapy on the airway microbiota in asthma

There is interest in the use of macrolide antibiotics in asthma. Macrolides have been shown to improve airway hyper-responsiveness (AHR) and measures of airway inflammation.1 The degree of AHR may relate to the microbiota present in the airways,2 with a recent study reporting that patients with asthma with a significant improvement in AHR following treatment with clarithromycin had a higher bacterial diversity prior to treatment.3 To our knowledge, the impact on the asthmatic airway microbiota of an antibiotic has not been reported and we therefore set out to establish if macrolide therapy was associated with a change in airway microbiota in asthma.

Resource-dependent attenuation of species interactions during bacterial succession.

Bacterial communities are vital for many economically and ecologically important processes. The role of bacterial community composition in determining ecosystem functioning depends critically on interactions among bacterial taxa. Several studies have shown that, despite a predominance of negative interactions in communities, bacteria are able to display positive interactions given the appropriate evolutionary or ecological conditions. We were interested in how interspecific interactions develop over time in a naturalistic setting of low resource supply rates. We assembled aquatic bacterial communities in microcosms and assayed the productivity (respiration and growth) and substrate degradation while tracking community composition. The results demonstrated that while bacterial communities displayed strongly negative interactions during the early phase of colonisation and acclimatisation to novel biotic and abiotic factors, this antagonism declined over time towards a more neutral state. This was associated with a shift from use of labile substrates in early succession to use of recalcitrant substrates later in succession, confirming a crucial role of resource dynamics in linking interspecific interactions with ecosystem functioning.

A relationship between Pseudomonal growth behaviour and cystic fibrosis patient lung function identified in a metabolomic investigation.

Chronic polymicrobial lung infections in adult cystic fibrosis patients are typically dominated by high levels of Pseudomonas aeruginosa. Determining the impact of P. aeruginosa growth on airway secretion composition is fundamental to understanding both the behaviour of this pathogen in vivo, and its relationship with other potential colonising species. We hypothesised that the marked differences in the phenotypes of clinical isolates would be reflected in the metabolite composition of spent culture media. 1H NMR spectroscopy was used to characterise the impact of P. aeruginosa growth on a synthetic medium as part of an in vitro CF lower airways model system. Comparisons of 15 CF clinical isolates were made and four distinct metabolomic clusters identified. Highly significant relationships between P. aeruginosa isolate cluster membership and both patient lung function (FEV1) and spent culture pH were identified. This link between clinical isolate growth behaviour and FEV1 indicates characterisation of P. aeruginosa growth may find application in predicting patient lung function while the significant divergence in metabolite production and consumption observed between CF clinical isolates suggests dominant isolate characteristics have the potential to play both a selective role in microbiota composition and influence pseudomonal behaviour in vivo.

Abundance determines the functional role of bacterial phylotypes in complex communities

Bacterial communities are essential for the functioning of the Earth’s ecosystems1. A key challenge is to quantify the functional roles of bacterial taxa in nature to understand how the properties of ecosystems change over time or under different environmental conditions2. Such knowledge could be used, for example, to understand how bacteria modulate biogeochemical cycles3, and to engineer bacterial communities to optimize desirable functional processes4. Communities of bacteria are, however, extraordinarily complex with hundreds of interacting taxa in every gram of soil and every millilitre of pond water5. Little is known about how the tangled interactions within natural bacterial communities mediate ecosystem functioning, but high levels of bacterial diversity have led to the assumption that many taxa are functionally redundant6. Here, we pinpoint the bacterial taxa associated with keystone functional roles, and show that rare and common bacteria are implicated in fundamentally different types of ecosystem functioning. By growing hundreds of bacterial communities collected from a natural aquatic environment (rainwater-filled tree holes) under the same environmental conditions, we show that negative statistical interactions among abundant phylotypes drive variation in broad functional measures (respiration, metabolic potential, cell yield), whereas positive interactions between rare phylotypes influence narrow functional measures (the capacity of the communities to degrade specific substrates). The results alter our understanding of bacterial ecology by demonstrating that unique components of complex communities are associated with different types of ecosystem functioning.Using natural tree-hole microbial communities, the authors show that bacterial abundance is related to their functional roles, with abundant phylotypes driving broad functional measures and rarer phylotypes implicated in more specialized measures.

Contributions of Composition and Interactions to Bacterial Respiration Are Reliant on the Phylogenetic Similarity of the Measured Community

Bacterial diversity underpins many ecosystem functions; however, the impact of within-species variation on the relationship between diversity and function remains unclear. Processes involving strain differentiation, such as niche radiation, are often overlooked in studies that focus on phylogenetic variation. This study used bacterial isolates assembled in two comparable microcosm experiments to test how species variation affected ecosystem function. We compared the relationship between diversity and activity (CO2 production) in increasingly diverse multispecies microcosms and with multiple ecotypes of a single species. The bacteria used were isolated from a low-diversity environment and are species of potential clinical significance such as Pseudomonas aeruginosa. All isolates were profiled for single carbon source utilisation. These data showed an increased breadth of resource use in the multiple ecotypes when compared to the mixed-species. The study observed significantly increasing respiration in more complex mixed-species assemblages, which was not observed when ecotypes of a single species were combined. We further demonstrate that the variation observed in the bacterial activity was due to the roles of each of the constituent isolates; between different species, the interactions between the isolates drove the variation in activity, whilst in single species, assemblage variation was due to which isolates were present. We conclude that both between- and within-species variations play different roles in community function, although through different mechanisms, and should be included in models of changing diversity and ecosystem functioning.