Children undergoing treatment for severe acute malnutrition lack an effective gut microbiome, which impairs their ability to use dietary fibre, hindering their recovery, according to a new study led by the Quadram Institute.

By studying the microbiomes of children hospitalised with severe acute malnutrition, the research teams found a lack of diversity in the microbes present that meant they couldn’t ferment the fibre inulin, which is commonly used as a prebiotic.

The findings will support the development and refinement of therapies that support beneficial fermentation by the microbiome, to improve their recovery and reduce the devastating impact of childhood undernutrition worldwide.

Globally, around 200 million children under 5 live with the long-term effects caused by a severe lack of food, and half of childhood deaths are linked directly or indirectly to undernutrition. Although a global problem, the vast burden of childhood undernutrition is borne by low- and middle-income countries in sub-Saharan Africa and South Asia.

One of the most serious forms, called severe acute malnutrition, is characterised by very low body weight and visible wasting, with one in five children hospitalised dying through lack of nutrients, or from infections taking advantage of a depleted immune system.

Treatments based on World Health Organisation guidelines involve milk-based feeds to immediately provide sugars, proteins and fats that support weight gain. Often antibiotics are also provided to counter infections. Rehabilitation continues with ready-to-use therapeutic feeds that help recovering children regain weight. However, over the longer-term, children hospitalised with severe acute malnutrition remain vulnerable to infection and re-hospitalisation.

One reason for this lies in the gut microbiome, which is dramatically altered in severe acute malnutrition. This impacts absorption of nutrients, and the release beneficial fermentation products as well as immunity and susceptibility to disease-causing gut microbes. Antibiotics to counter infections further decrease the microbiome’s diversity and effectiveness to aid healthy recovery.

Trials of supplements to boost the microbiome have had mixed results, mostly focused on mild malnutrition. Recent studies by Imperial College and Mbale Clinical Research Institute in Uganda found that some microbiome diversity and function could be boosted if the therapeutic diet of children with severe acute malnutrition was enriched with a supplement derived from chickpeas, a cheap and locally available resource.

A key to success of microbiota-supporting supplements lies in fermentation, where the microbes break down suitable carbohydrates to release short chain fatty acids, which support a gut health and the immune system.

But in severely disrupted microbiomes, there is a question of whether there are enough suitable microbes left to carry out this vital fermentation.

To address this, Dr Akshay Bisht, working in Dr Fred Warren’s group in the Quadram Institute on the Norwich Research Park sought to determine the fermentability of different potential microbiome-supporting foods by the gut microbes of children with severe acute malnutrition. The study was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC), both part of UKRI.

They were sent samples of microbiomes of hospitalised children obtained from their faeces, with their parents’ consent, as part of the trial of chickpea-based feed by Imperial College.

The bacteria in these faecal samples were then used to accurately mimic the gut microbiome in models of the colon in the Quadram’s laboratories.

These microbiomes were from patients who had been treated for severe acute malnutrition for seven days. They showed very poor bacterial diversity, dominated by potentially infectious bacteria like E.coli  and Klebsiella and lacking the bacteria associated with a healthy microbiome.

The researchers then “fed” these microbiomes four different carbohydrate sources, representing different feeding regimes, to study how the microbes from the children could ferment them.

They used the infant formula WHO recommend for recovery from malnutrition, and then also additionally supplemented this with human milk oligosaccahrides (HMOs), which are sugars that mimic those found in human breast milk.

They also tested the chickpea-based feed developed in the previous studies by Imperial College to support microbial recovery.

The final fibre included in the study was inulin, a plant-derived fibre that’s very commonly used as a prebiotic for its known ability to support beneficial fermentation in a healthy gut microbiome.

The results, published in the journal iScience, showed that fermentation by the gut microbiome was much lower in the presence of inulin, compared to the other carbohydrates tested.

The experiment was repeated, but this time using faecal samples from the same children collected 90 days after therapeutic feeding treatment. These microbiomes had a restored facility to ferment inulin, and analysis of the microbiome showed an improved bacterial diversity and higher levels of the bacterial enzymes to breakdown inulin.

This illustrates the importance of carefully selecting the right type of supplementation to support microbial diversity, and restoring it when lost, and the importance of profiling the microbiome at different stages of recovery.

This was a limited study with a small number of samples, but given the scale and impact of severe malnutrition, there is an urgent need to better understand how it affects the microbiome, how it ferments carbohydrates, to provide the best possible options to support not only the treatment of malnutrition, but also long-term recovery.

Reference: Gut microbial diversity impacts carbohydrate fermentation by children with severe acute malnutrition, Akshay Bisht, Jennifer Ahn-Jarvis, Kendall Corbin, Suzanne Harris, Perla Troncoso-Rey, Peter Olupot-Olupot, Nuala Calder, Kevin Walsh, Kathryn Maitland, Gary Frost, Frederick J. Warren, iScience, DOI: 10.1016/j.isci.2026.114640