<i>FUT2</i>genotype influences lung function, exacerbation frequency and airway microbiota in non-CF bronchiectasis

Taylor, Steven; Woodman, Richard; Chen, Alice C.‐H.; Burr, Lucy; Gordon, David L.; McGuckin, Michael A.; Wesselingh, Steve; Rogers, Geraint B.

doi:10.1136/thoraxjnl-2016-208775

Cited by 41 publications

(27 citation statements)

References 43 publications

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“…33 More interesting perhaps is the recent study of the Fucosyltransferase 2 ( FUT2 ) genotype in non-CF bronchiectasis and its impact on P. aeruginosa dominance of the microbiota present. 34 For asthma, it is notable that the genetic risk factors identified by genomewide association studies are expressed by or within the respiratory epithelium, perhaps reflecting the importance of the respiratory microbiome. 35 Understanding more about host-microbiome interactions could follow from comparing gene expression in airway samples to microbial communities in various diseases.…”

Section: Host Factorsmentioning

confidence: 99%

The lung microbiome in health and disease

Moffatt¹,

Cookson²

2017

Clinical Medicine

160

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The Human Microbiome Project began 10 years ago, leading to a signifi cant growth in understanding of the role the human microbiome plays in health and disease. In this article, we explain with an emphasis on the lung, the origins of microbiome research. We discuss how 16S rRNA gene sequencing became the fi rst major molecular tool to examine the bacterial communities present within the human body. We highlight the pitfalls of molecular-based studies, such as false fi ndings resulting from contamination, and the limitations of 16S rRNA gene sequencing. Knowledge about the lung microbiome has evolved from initial scepticism to the realisation that it might have a signifi cant infl uence on many illnesses. We also discuss the lung microbiome in the context of disease by giving examples of important respiratory conditions. In addition, we draw attention to the challenges for metagenomic studies of respiratory samples and the importance of systematic bacterial isolation to enable host-microbiome interactions to be understood. We conclude by discussing how knowledge of the lung microbiome impacts current clinical diagnostics.

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Section: Host Factorsmentioning

confidence: 99%

The lung microbiome in health and disease

Moffatt¹,

Cookson²

2017

Clinical Medicine

160

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“…This relationship could inform the stratification of patient populations and the prediction of adverse events. For example, stratification of patients with noncystic fibrosis bronchiectasis by secretor status identified that chronic airway infection, lung function, and pulmonary exacerbation frequency were higher in secretor individuals [67].…”

Section: Using Glycosyltransferase Characteristics To Inform Policy Amentioning

confidence: 99%

Infection’s Sweet Tooth: How Glycans Mediate Infection and Disease Susceptibility

Taylor

McGuckin

Wesselingh

et al. 2018

Trends in Microbiology

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Glycans form a highly variable constituent of our mucosal surfaces and profoundly affect our susceptibility to infection and disease. The diversity and importance of these surface glycans can be seen in individuals who lack a functional copy of the fucosyltransferase gene, FUT2. Representing around one-fifth of the population, these individuals have an altered susceptibility to many bacterial and viral infections and diseases. The mediation of host-pathogen interactions by mucosal glycans, such as those added by FUT2, is poorly understood. We highlight, with specific examples, important mechanisms by which host glycans influence infection dynamics, including by: acting as pathogen receptors (or receptor-decoys), promoting microbial stability, altering the physical characteristics of mucus, and acting as immunological markers. We argue that the effect glycans have on infection dynamics has profound implications for many aspects of healthcare and policy, including clinical management, outbreak control, and vaccination policy.

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“…dominated’ sample on sequencing and one hypothesis is therefore that the glycan differences lead to an increased susceptibility to Pseudomonas infection and a less favourable clinical course. However, as the authors acknowledge, the lack of Pseudomonas fuctose catabolism or adherence mechanisms specific for (1,2) fucosylated glycan makes a direct link less likely 5. The alternative hypothesis that more subtle changes in the microbial community between secretors and non-secretors could lead directly to a worse prognosis or via the increased susceptibility to Pseudomonas was also not supported by the lack of demonstrable difference in the microbiome analysis.…”

mentioning

confidence: 92%

“…In Thorax , Taylor et al 5 investigate one possible genetic predisposition to a worse bronchiectasis phenotype. They used the well-published, prospective cohort from the BLESS trial, which assessed the impact of long-term erythromycin on exacerbation rate 6.…”

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confidence: 99%