A medical solution aimed at malnourished children

It may not be the kind of thing people choose to discuss over the dinner table, but faecal transplants are gaining increasing acceptance as medical procedures as scientists learn more about the significance of the multitudes of bacteria inhabiting the human body.

There is growing evidence that many diseases are associated with an out-of-kilter gut microbiome. Injecting stool from a healthy donor into a patient’s digestive tract is an attempt to restore the good bugs and diminish or eliminate the bad. Faecal transplants have been so successful in combating Clostridium difficile — which causes severe diarrhoea — that they are included in the US guidelines for treating this life-threatening condition.
 

It may not be the kind of thing people choose to discuss over the dinner table, but faecal transplants are gaining increasing acceptance as medical procedures

Scientists are now investigating the scope for using the procedure to treat other ailments, ranging from ulcerative colitis to multiple sclerosis.

There are dozens of faecal transplant trials under way around the world, and the first African study, called THRIVE, is set to begin at the Red Cross War Memorial Children’s Hospital in Cape Town in September. It is a collaborative effort between scientists at UCT and the US nonprofit stool bank OpenBiome.

The THRIVE (transfer of healthy gut flora for restoration of intestinal microbiota via enema) trial is a small phase 1 study that will investigate whether faecal transplants can help severely malnourished children who fail to develop even after their nutritional needs are met.

Globally, about 35% of children who have severe acute malnutrition fail standard therapy, which includes specially formulated high-calorie food, says UCT’s Shrish Budree, a research fellow at OpenBiome and one of the investigators on the trial.

"These kids don’t achieve their full growth potential and end up stunted, with an increased risk of infections and mortality," he says.

"In the longer term, they are likely to be less productive adults, which has bigger implications for society at large. There is currently no alternative for the kids who don’t respond to standard therapy."

Previous research has shown that children who have been severely malnourished sustain abnormal digestive tract bacteria even months after normal feeding resumes, suggesting that their altered gut flora prevent them from absorbing the nutrients they need to develop.

The hope with the THRIVE study is that faecal transplants from carefully selected donors will change the bacterial balance in their guts for the better, enabling them to get all the benefits they need from their food.
 

In South Africa, there were more than 26,700 cases of severe childhood malnutrition in 2015.

Given the scale of severe acute malnutrition, which affects 20-million children under the age of five worldwide each year and kills about a million of them, the study has a potential global impact.

In South Africa, there were more than 26,700 cases of severe childhood malnutrition in 2015, says Budree.

THRIVE has funding from the Bill & Melinda Gates Foundation, Child Relief International Foundation and The Thrasher Research Fund.

The trial, which has been approved by the SA Health Products Regulatory Authority, will enrol 20 children under the age of five, who will receive a single enema containing a slurry of donated stool provided by the Boston-based OpenBiome.

Donors have to be aged between 18 and 50 and are subjected to a battery of tests. Only 3% of them make the grade, says OpenBiome’s clinical programme director, Majdi Osman, the study’s principal investigator. Safety is paramount, he says, cautioning against anyone considering trying a DIY faecal transplant at home.
 

There are dozens of faecal transplant trials under way around the world, and the first African study, called THRIVE, is set to begin at the Red Cross War Memorial Children’s Hospital in Cape Town in September.

Potential donors are screened even more rigorously than blood donors, as they have to be clear of any health issues that have been linked to the gut microbiome, such as auto-immune disorders, Osman says.

While stool from US patients may not be ideal, it is not feasible to screen potential donors in South Africa at this stage as there is no infrastructure to do so, says Budree.

"There may be differences in diet between the United States and South Africa that could mean the donor microbes don’t thrive after the transplant, but we don’t think there is any safety risk," Budree says. "We aim to have local donors in the next study we design."

The endgame of the research is to identify the strains of bacteria that are lacking in the children who fail to recover from malnutrition and those that are too abundant.

If the hypothesis that restoring the microbial health of these children holds true, the next step might be to culture the good bacteria and add them to a food that appeals to children, says Budree.