Faecal microbiota transplantation: what's beyond Clostridium difficile infection?

Over the last decade, major advancements have been made in our understanding of both the beneficial and detrimental role that microorganisms play in our innate functioning. Research into the intestinal microbiota has moved from the laboratory into our medical clinics and is being put forth as an effective therapy for a range of medical conditions, not only limited to the gastrointestinal system. The clearest example of this progression has been in the treatment of Clostridium difficile infection; however, faecal microbiota transplantation has also been shown to have a positive effect in the treatment of inflammatory disorders, such as ulcerative colitis. In this review article, we will appraise the existing literature examining the role the intestinal microbiota plays in the pathogenesis of disease and the therapeutic utility of faecal microbiota transplantation in restoring homeostasis. In many cases, these studies are in a preclinical setting, are small in scale and often are not placebo-controlled; however, the results from these studies report interesting associations between intestinal dysbiosis and disease development, as well as the beneficial effects of faecal microbiota transplantation in reversing this process.

Identification of a novel cystic fibrosis mutation in three patients of South Asian descent.

INTRODUCTION: The cystic fibrosis (CF) clinical profile and associated CFTR mutation spectrum is poorly understood in the South Asian population. This is likely due to the lack of diagnostic resources and the absence of a centralised CF database and screening programme, despite a relatively large proportion of the global population. METHODS: Following identification of a previously unreported CFTR mutation (c.2805_2810delinsTCAGA; p.(Pro936Ginfs*6)) in a newly diagnosed patient of Indian descent, we interrogated national registries for other cases. RESULTS: We identified three European-born subjects of South Asian descent with CF due to a novel CFTR mutation. All three subjects presented in infancy and each had a severe phenotype with intestinal complications as a presenting feature. Two subjects were diagnosed prior to the advent of universal screening. Preliminary genetic screening failed to identify the causative mutation in all three patients. CONCLUSION: Our work highlights the value of extended or targeted genotyping in selected populations. It also demonstrates the benefit of routine collaboration between national registries. This will promote the identification of novel mutations; leading to greater understanding of genotype-phenotype associations, improved individual prognostication and ultimately the improved availability of novel precision therapies. This collaboration is essential if we are to achieve health equality for people with CF living in resource-limited settings.

The implications and management of cystic fibrosis screen positive, inconclusive diagnosis patients.

Newborn screening and extensive genetic analysis has led to the recognition of a cohort of infants with an equivocal diagnosis of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) disease. This paper reviews the comprehensive approach required for diagnosis of Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID) and uses an illustrative case with p.Asp1152His (D1152H) mutation to examine the varying clinical phenotype seen amongst CFSPID patients. Whilst infants are well at diagnosis, uncertainties about cystic fibrosis (CF) disease progression indicate the importance of monitoring and early specialist involvement. However, over-medicalisation can cause significant psychosocial impact on patients' and families. The complexities underlying the surveillance and long-term management of patients with CFSPID are explored.