Investigating the Microbiome as a Driver of Inflammation and Growth Following Acute Illness

Project No: NC-18
Intake: 2024 KIR Non Clinical

PROJECT OVERVIEW

The medical and nutritional management of acutely ill, undernourished children in low- and middle-income (LMIC) countries is aimed at reducing risk of death and supporting convalescence and rapid weight gain. Currently, however, such children remain at risk and some have poor catch-up growth post hospital discharge.

The role of systemic inflammation (SI) in growth failure is clear from studies of inflammatory conditions in high-income settings, and the consequences of persistent immune-stimulation could thus represent an important additional factor in the growth failure of children in LMIC settings.

Microbial drivers of persistent SI post discharge may include specific enteric and systemic pathogens, altered structure, composition, and function of the microbiome, and translocation of microbial products. However, the interplay between intestinal pathogens, intestinal inflammation, microbiome, microbial translocation and SI and their relation to post discharge catch-up growth among acutely ill children is not well known.

This project will investigate the microbiome impact on SI and growth. It will make use of data and biological samples collected through the Childhood Acute Illness and Nutrition (CHAIN) Network. In particular, it will focus on a longitudinal cohort for whom microbiome data have been collected, alongside markers of enteric inflammation and microbial product translocation.

The aim will be to understand how development of the microbiome is impacted following acute illness, and to identify microbiome correlates of microbial product translocation and enteric and systemic inflammation that may impact growth.

KEYWORDS (5 WORDS)

Microbiome, Nutrition, Inflammation, Growth, Paediatrics

TRAINING OPPORTUNITIES

The successful candidate will be expected to work closely with supervisors at the KEMRI-Wellcome Programme, the Wellcome Sanger Institute, and the University of Oxford. They will be trained in the bioinformatic analysis of microbiome sequence and metabolomic data and will have the opportunity to integrate these with other clinical and multiomic datasets collected through the CHAIN Network. They will additionally benefit from being part of the Africa-Oxford Initiative and will have the opportunity to present work at national and international scientific conferences.

KEY PUBLICATIONS (5 maximum)

Njunge, J.M., Gwela, A., Kibinge, N.K. et al. Biomarkers of post-discharge mortality among children with complicated severe acute malnutrition. Sci Rep 9, 5981 (2019). https://doi.org/10.1038/s41598-019-42436-y

Amadi, B., Zyambo, K., Chandwe, K. et al. Adaptation of the small intestine to microbial enteropathogens in Zambian children with stunting. Nat Microbiol 6, 445–454 (2021). https://doi.org/10.1038/s41564-020-00849-w

Njunge J.M., Tickell K., Diallo A.H. et al. The Childhood Acute Illness and Nutrition (CHAIN) network nested case-cohort study protocol: a multi-omics approach to understanding mortality among children in sub-Saharan Africa and South Asia Gates Open Res 6:77 (2022). https://doi.org/10.12688/gatesopenres.13635.2