Emerging pathogenic links between microbiota and the gut-lung axis

© 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. The microbiota is vital for the development of the immune system and homeostasis. Changes in microbial composition and function, termed dysbiosis, in the respiratory tract and the gut have recently been linked to alterations in immune responses and to disease development in the lungs. In this Opinion article, we review the microbial species that are usually found in healthy gastrointestinal and respiratory tracts, their dysbiosis in disease and interactions with the gut-lung axis. Although the gut-lung axis is only beginning to be understood, emerging evidence indicates that there is potential for manipulation of the gut microbiota in the treatment of lung diseases

Disease-associated gut microbiome and metabolome changes in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is the third commonest cause of death globally, and manifests as a progressive inflammatory lung disease with no curative treatment. The lung microbiome contributes to COPD progression, but the function of the gut microbiome remains unclear. Here we examine the faecal microbiome and metabolome of COPD patients and healthy controls, finding 146 bacterial species differing between the two groups. Several species, including Streptococcus sp000187445, Streptococcus vestibularis and multiple members of the family Lachnospiraceae, also correlate with reduced lung function. Untargeted metabolomics identifies a COPD signature comprising 46% lipid, 20% xenobiotic and 20% amino acid related metabolites. Furthermore, we describe a disease-associated network connecting Streptococcus parasanguinis_B with COPD-associated metabolites, including N-acetylglutamate and its analogue N-carbamoylglutamate. While correlative, our results suggest that the faecal microbiome and metabolome of COPD patients are distinct from those of healthy individuals, and may thus aid in the search for biomarkers for COPD

Long-term carbon sink in Borneo's forests halted by drought and vulnerable to edge effects

Less than half of anthropogenic carbon dioxide emissions remain in the atmosphere. While carbon balance models imply large carbon uptake in tropical forests, direct on-the-ground observations are still lacking in Southeast Asia. Here, using long-term plot monitoring records of up to half a century, we find that intact forests in Borneo gained 0.43 Mg C ha‾¹ per year (95% CI 0.14—0.72, mean period 1988-2010) above-ground live biomass. These results closely match those from African and Amazonian plot networks, suggesting that the world's remaining intact tropical forests are now en masse out-of-equilibrium. Although both pan-tropical and long-term, the sink in remaining intact forests appears vulnerable to climate and land use changes. Across Borneo the 1997-1998 El Niño drought temporarily halted the carbon sink by increasing tree mortality, while fragmentation persistently offset the sink and turned many edge-affected forests into a carbon source to the atmosphere

Perspectives from the NanoSafety Modelling Cluster on the validation criteria for (Q)SAR models used in nanotechnology

Nanotechnology and the production of nanomaterials have been expanding rapidly in recent years. Since many types of engineered nanoparticles are suspected to be toxic to living organisms and to have a negative impact on the environment, the process of designing new nanoparticles and their applications must be accompanied by a thorough exposure risk analysis. (Quantitative) Structure-Activity Relationship ([Q]SAR) modelling creates promising options among the available methods for the risk assessment. These in silico models can be used to predict a variety of properties, including the toxicity of newly designed nanoparticles. However, (Q)SAR models must be appropriately validated to ensure the clarity, consistency and reliability of predictions. This paper is a joint initiative from recently completed European research projects focused on developing (Q)SAR methodology for nanomaterials. The aim was to interpret and expand the guidance for the well-known “OECD Principles for the Validation, for Regulatory Purposes, of (Q)SAR Models”, with reference to nano-(Q)SAR, and present our opinions on the criteria to be fulfilled for models developed for nanoparticles

Microbiomes in respiratory health and disease: An Asia-Pacific perspective

© 2017 Asian Pacific Society of Respirology There is currently enormous interest in studying the role of the microbiome in health and disease. Microbiome's role is increasingly being applied to respiratory diseases, in particular COPD, asthma, cystic fibrosis and bronchiectasis. The changes in respiratory microbiomes that occur in these diseases and how they are modified by environmental challenges such as cigarette smoke, air pollution and infection are being elucidated. There is also emerging evidence that gut microbiomes play a role in lung diseases through the modulation of systemic immune responses and can be modified by diet and antibiotic treatment. There are issues that are particular to the Asia-Pacific region involving diet and prevalence of specific respiratory diseases. Each of these issues is further complicated by the effects of ageing. The challenges now are to elucidate the cause and effect relationships between changes in microbiomes and respiratory diseases and how to translate these into new treatments and clinical care. Here we review the current understanding and progression in these areas

Autism-related dietary preferences mediate autism-gut microbiome associations.

There is increasing interest in the potential contribution of the gut microbiome to autism spectrum disorder (ASD). However, previous studies have been underpowered and have not been designed to address potential confounding factors in a comprehensive way. We performed a large autism stool metagenomics study (n = 247) based on participants from the Australian Autism Biobank and the Queensland Twin Adolescent Brain project. We found negligible direct associations between ASD diagnosis and the gut microbiome. Instead, our data support a model whereby ASD-related restricted interests are associated with less-diverse diet, and in turn reduced microbial taxonomic diversity and looser stool consistency. In contrast to ASD diagnosis, our dataset was well powered to detect microbiome associations with traits such as age, dietary intake, and stool consistency. Overall, microbiome differences in ASD may reflect dietary preferences that relate to diagnostic features, and we caution against claims that the microbiome has a driving role in ASD

Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia

Upregulation of the immune response may be involved in the pathogenesis of schizophrenia with changes occurring in both peripheral blood and brain tissue. To date, microarray technology has provided a limited view of specific inflammatory transcripts in brain perhaps due to sensitivity issues. Here we used SOLiD Next Generation Sequencing to quantify neuroimmune mRNA expression levels in the dorsolateral prefrontal cortex of 20 individuals with schizophrenia and their matched controls. We detected 798 differentially regulated transcripts present in people with schizophrenia compared with controls. Ingenuity pathway analysis identified the inflammatory response as a key change. Using quantitative real-time PCR we confirmed the changes in candidate cytokines and immune modulators, including interleukin (IL)-6, IL-8, IL-1b and SERPINA3. The density of major histocompatibility complex-II-positive cells morphologically resembling microglia was significantly increased in schizophrenia and correlated with IL-1b expression. A group of individuals, most of whom had schizophrenia, were found to have increased inflammatory mRNA expression. In summary, we have demonstrated changes in an inflammatory response pathway that are present in 40% of people diagnosed with schizophrenia. This suggests that therapies aimed at immune system attenuation in schizophrenia may be of direct benefit in the brain