Clinical Research Directory

Respiratory Microbioma and Respiratory Complications After Hematopoietic Stem Cell Transplantion

Allogeneic haematopoietic stem cell transplantation (AHSCT) is a therapeutic resource for many haemopathies. The number of HSCTs has risen sharply in recent years due to the use of attenuated conditioning, which has increased the risk of non-haematological complications. Pulmonary pathologies are a frequent cause of complications following HSCA, both infectious and non-infectious(1,3,4). Among these, late non-infectious pulmonary complications (LNIPC), all taken together, occur in 25% of post-HSCA cases(1). These NIPCs, the most common of which is bronchiolitis obliterans, significantly alter the prognosis(4,5). The pathophysiology of CPTNI is poorly understood, but it seems that the occurrence of a viral respiratory infection (pre- or post-ACSH) may be a potential trigger for the onset of CPTNI(1). These viral infections can become "chronic", given that viral clearance is impaired by the underlying immunodepression, and can thus cause chronic inflammation leading to the fibrosing and irreversible process of obliterative bronchiolitis(6). Given the prognostic importance of this type of CPTNI, it seems essential to gain a better understanding of its pathophysiology, which may involve a number of mechanisms: cellular expression of the graft and its evolution, disruption of the host response (innate immunity) following viral infection, influence of the microbiome and alteration of epithelial repair(1,3,5). Interest in the digestive and respiratory microbiome has been growing in recent years(7-9). The literature is gradually being enriched with data on the links between infection, the microbiome and chronic respiratory pathology and, in the post-HSCA context, a potential link between the enteric microbiome and Chronic Graft Versus Host Disease (cGVHD). A pilot study comparing respiratory microbiomes using sequencing and metatranscriptomic analysis on 20 respiratory samples (nasopharyngeal swab and bronchoalveolar lavage pairs) taken under the conditions of the proposed study showed that the technique was highly feasible and highly sensitive. The aim of this study is therefore to use meta-genomics to investigate the respiratory virome/microbiome in a population of patients who have undergone HSCA: eukaryotic and prokaryotic viruses, bacterial expression and the expression (meta-transcriptomics) of graft-derived cell lines and their possible association with the occurrence of post-HSCA respiratory complications (infectious and non-infectious). No study has assessed the link between the composition of the respiratory virome/microbiome and the occurrence of respiratory events (infectious and CPTNI post ACSH), but also more broadly the link with the composition of the microbiome in the broad sense (respiratory virome, respiratory and digestive microbiota). The aim of this study is to establish a respiratory viral and bacterial map as a possible biomarker of the occurrence of respiratory events (infectious and CPTNI), thus enabling more personalised monitoring of patients at risk of CPTNI and management of immunosuppressive treatment of patients at risk of an infectious episode, with risk assessment based on the composition of the respiratory virome. The interest of this study is that it is multidisciplinary and transdisciplinary, studying the respiratory pathologies and infections of haematology patients and combining clinical and fundamental research, with expected spin-offs for direct patient care (personalised monitoring and management of immunosuppressive treatments).

Microbiome Alterations With Xylitol (MAX) in Pregnancy

The purpose of this study is to understand if chewing xylitol-gum initiated before 20 weeks of pregnancy and continued until delivery affects the bacteria that are found in the oral and vaginal cavities, signs of inflammation within the gingiva of the oral cavity, the health of the tissues in the mouth (clinical parameters of periodontal disease) and placentae, and the bacteria in the mouth and gut of newborns among pregnant individuals in Malawi. In addition, we will evaluate the impact of xylitol-containing chewing gum use during pregnancy on the offsprings neurodevelopment at approximately 6- and 18-months corrected age.

Augmented Response of Volatile Biomarkers in Assessment of Oesophagogastric Cancer (AROMA 1 / BIORESOURCE)

Cancer of the stomach and oesophagus is among the world's top five cancers. Survival rates are very poor as the disease presents late and early symptoms are non-specific. The study team has developed a non-invasive test for cancers of the stomach and oesophagus based on the detection of volatile organic compounds in exhaled breath. These compounds are known to be produced by both cancers as well as cancer associated bacteria within the gut. The proposed innovation is to improve the accuracy of this test by investigating whether simple metabolic substrates can increase the production of these volatile organic compounds by both the tumour and its associated bacteria.