Novel gastrointestinal tools (GI Tools) for evaluating gut functional capacity in adults with environmental...

Environmental enteropathy (EE) is a highly prevalent subclinical inflammatory intestinal disorder associated with growth failure, impaired neurocognitive development, poor response to oral vaccines, and micronutrient deficiencies. However, EE research and clinical trials are hampered by the lack of non-invasive tools for measuring intestinal function in detail. This study aims to develop new tools for the measurement of multiple domains of gut functional capacity.

The GI TOOLS project is a cross-sectional study that will recruit adults aged 18-65 years with EE in Lusaka, Zambia. Each participant will undergo assessment of gut functional capacity using novel near-point-of-care tools and provide multiple samples for detailed laboratory analyses. Participants will also undergo endoscopy for collection of duodenal biopsies. Novel techniques include stable isotopes approaches to measuring digestion, absorption, and bidirectional transmucosal amino acid flux, a non-invasive fluorescence tool for real-time evaluation of gut permeability, and assessment of reverse permeation of intravenous antibiotics to be carried out separately in Zimbabwe. Stool and duodenal microbiome sequencing using MinION sequencing, metabolome analysis applied to plasma and intestinal fluids, blood immune cell phenotyping, in vitro epithelial barrier models, and duodenal immunohistochemistry will also be used to explore EE in depth. These will all be integrated with gold standard histology and mucosal morphometry, alongside lactulose permeation data, and stool and plasma biomarker analysis. The protocol has been approved by ethics committees and regulators in Zambia, Zimbabwe, and the UK. Participants will give informed consent before they can participate.

Based on this extensive phenotyping, tests will be developed which can be simplified and refined for use in adults and children with EE, and for clinical trials. Findings from this project will be disseminated through in-person meetings with caregivers and regulatory bodies, presentations at conferences and in peer-reviewed journals.