Environmental enteropathy (EE) is a syndrome affecting the gut characterised by villus blunting, reduced nutrient absorption and microbial translocation in children and adults experiencing a high burden of enteric infection due to inadequate access to clean water and sanitation.

We will conduct coordinated randomised controlled trials in six countries to determine if supplementation with indispensable amino acids (IAAs) can improve intestinal barrier dysfunction in six geographically diverse populations of 18–36 months old children with stunting or severe stunting. All trials will measure the same primary outcomes while secondary outcomes will be measured on a per-trial basis using standardised protocols across the project. The primary endpoint will be change in gut permeability as assessed by the lactulose/rhamnose ratio. Secondary endpoints include changes in amino acid and carbohydrate absorption using novel, isotope tracer tests. Other prespecified outcome measures include changes in EE biomarkers and child weight. IAA supplementation will be given daily for 28 days and evaluation of the major endpoints will be at baseline and after 28 days of supplementation.

Ethical approval will be obtained from the Research Ethics Committee at each participating site. Caregivers will provide written informed consent for each participant. Findings will be disseminated through peer-reviewed journals, conference presentations and face-to-face meetings with participant caregivers.

CTRI: CTRI/2024/06/069187 (India); ClinicalTrials.gov (NCT06617130, Malawi; NCT06676215, Philippines and NCT07256028, Morocco); Ongoing (Zambia); Ongoing (Morocco); PACTR: (PACTR202311714091884, Ghana).

The Infant Gut Bacterial Study in Nigeria (INBUGS-NG) investigates how delivery mode, antibiotic exposure, feeding practices and environmental factors shape gut microbiome development and acquisition of antibiotic resistance genes (ARGs) during the first year of life in northern Nigeria.

Between February and July 2024, 90 mother–infant dyads were enrolled at a tertiary hospital in Kano city, Nigeria. This was a prospective longitudinal cohort with follow-ups at 10 scheduled time points: days 0, 1, 3, 5, 7, 14, 28, 90, 180 and 365. We also intensified stool sampling after infant antibiotic administration, enabling dense early-life sampling. To date, the cohort has contributed 480 infant stool samples, 232 maternal rectal swabs, 254 breast milk samples and 806 environmental samples (total 1772). In parallel, socio-demographic, clinical and cultural data were collected using Research Electronic Data Capture (REDCap) and household visit diaries.

Baseline data show that 84/90 mothers (93.3%) received postpartum antibiotics, and 26/90 infants (28.9%) received antibiotics within the first 3 months of life. Only 8% of infants were exclusively breastfed, with early water supplementation common. Caesarean deliveries accounted for 25% of births, and the mean gestational age was 38.5 weeks. Across the cohort, high retention was achieved, and the study has generated a unique long-read metagenomic resource from an African infant population, with analyses ongoing.

Shotgun long-read metagenomic sequencing (Oxford Nanopore) will enable strain-level and plasmid-level profiling of microbial communities and ARGs. Planned analyses include associations between early-life exposures and resistome dynamics, as well as cross-cohort comparisons with a parallel study in Pakistan. Follow-up will continue through 12 months.