A longitudinal analysis of the gut microbiome of stunted children infected with Human immunodeficiency virus (HIV) – a pilot project

In 2021, the United Nations Children’s Fund (UNICEF) reported 2.7 million children and adolescents living with HIV globally, with 88% living in Sub-Saharan Africa. Since the advent of universal anti-retroviral therapy (ART), the number of children dying from HIV worldwide has significantly reduced. With improved longevity, however, they are predisposed to metabolic conditions, such as diabetes, in their adulthood, which research studies have linked to the effects of chronic HIV infection and ART.

Stunted height, representative of chronic malnutrition and gut inflammation, is highly prevalent in children with HIV infection. Long term outcomes of nutritional stunting in children also include non-communicable diseases and cognitive delay later in life. While ART has improved growth trends in children on treatment from an early age, 30% of HIV-infected children remain stunted, posing an additional risk of developing these non-communicable diseases in adulthood. Due to poor understanding of the underlying causal factors, treatments to improve growth in stunted children are still lacking.

Therefore, this group of stunted HIV-infected children represents a vulnerable population at high risk of multi-morbidity, and Terishia Hariram’s project aims to pilot exploratory research that investigates underlying contributary factors related to the gut microbiome using novel next generation sequencing techniques.

The gut microbiome is a collection of micro-organisms found within the digestive tract, which plays a significant role in growth, development, and metabolism. Abnormal composition of the gut microbiome has recently been recognised as a major factor underlying many disease states, including both nutritional stunting and HIV-related inflammation. Hariram’s project aims to detect abnormalities and key characteristics of the gut microbiome composition and markers of gut inflammation in stunted HIV-infected children, in comparison to HIV-infected children with normal height, as well as HIV-uninfected children. 

This study has the potential to identify unique microbiome characteristics in a high risk group of children, that can inform future interventional studies, which aim to ultimately improve stunting and the long-term outcomes of these children. In addition, the identification of biomarkers of gut inflammation may create potential for risk-stratification of children and adolescents living with HIV who are at risk for stunting and non-AIDS related illnesses, to allow for earlier intervention. 

With the changing epidemiology of HIV infection in Sub-Saharan Africa since ART, the risk of non-AIDs related morbidity in children and adolescents on ART is highlighted. It is now a global and national research priority to monitor and improve the long-term outcomes of HIV-infected children on ART. Further research studies are needed to identify those at highest risk, understand what factors contribute to this risk and pilot innovative therapies to improve their outcomes.

SANTHE is an Africa Health Research Institute (AHRI) flagship programme funded by the Science for Africa Foundation through the DELTAS Africa programme; the Bill & Melinda Gates Foundation; Gilead Sciences Inc.; and the Ragon Institute of Mass General, MIT, and Harvard.