Venture into the interior

Prof Stephen O’Keefe is the director of the African Microbiome Institute.
Researchers at Stellenbosch University’s (SU) newly established African Microbiome Institute will be explorers entering a largely undiscovered world – the human microbiome.  
Acting as Director of the Institute is Prof Stephen O’Keefe, an internationally renowned researcher with some forty years’ experience in nutritional gastroenterology. He’ll be playing a dual role at SU and the University of Pittsburgh, where he’s professor of medicine and Director of the Centre for Intestinal Health and Nutrition Support. 
O’Keefe’s passion for nutritional medicine was sparked as a child. Growing up in Northern Rhodesia (now Zambia), he spent vacations accompanying his doctor father on clinic visits. “It was on these trips that I saw how nutrition was one of the key things that affected health,” he says.  
This interest lead to training in medicine (Guy’s Hospital) and human nutrition (London School of Hygiene and Tropical Medicine), followed by internal medicine and gastroenterology at Oxford and King’s College Hospital, and a fellowship in nutrition at Harvard and the Massachusetts Institute of Technology (MIT). 
In these settings, O’Keefe learned to help patients who couldn’t eat, using interventional techniques such as feeding through a vein or tube: “That’s the westernised idea of nutritional support.” 
But he also came to understand how gastrointestinal diseases vary dramatically around the world and in different communities. This realisation guided his clinical practice and research towards nutritional gastroenterology in both developed and less developed contexts.  
O’Keefe’s work on colon cancer is particularly influential. In a landmark 2015 study, he showed that switching between a low-fibre diet, high in meat and fat, and a high-fibre, low meat and low fat diet leads to profound changes in the gut microbiome, with important implications for cancer risk.  
There is huge potential for further breakthroughs in the rapidly developing field of microbiome research. This prospect has stirred in O’Keefe “a yearning to get back to Africa, to deal with more basic nutritional problems” – an impulse that has led him home to Southern Africa, and Stellenbosch University.  
A teeming, vital world 
The microbiome is the genetic material of the microbial population – microbiota such as bacteria, fungi, protozoa and viruses – in a particular environment, for example the human body.  
This is the territory researchers at the new Institute will be mapping out. It is a teeming and complex one: the number of genes present in one person’s microbiome is estimated at 200 times the number in the human genome, and scientists have only recently begun to realise their full biological importance. Evidence is mounting as to just how crucial a role the microbiome plays in fundamentals of health such as digesting food, producing vitamins, regulating the immune system and fighting disease.  
O’Keefe’s enthusiasm for this flourishing field is palpable: “It’s like discovering another organ within the body… It’s fascinating how much we’re learning about how the microbiome affects our health – both how it preserves health, and also how it can cause disease.”  
For example, there are studies looking at the role microbiota play in malnutrition and stunting. Other research explores how knowledge of the microbiome can be used to adapt to low-protein diets, or survive famine.  
The fibre puzzle 
What affects the microbiome more than anything else, is diet: a point well illustrated by the example of dietary fibre. Denis Burkitt, an Irish surgeon who worked in Africa after the Second World War, noted differences in disease patterns between Africans and Europeans, and is credited with first making the radical suggestion that the crucial factor was the relative deficiency of fibre in the westernised diet.  
This was confirmed by O’Keefe’s remarkable “diet switch” findings. Having noted that African Americans suffer a high incidence of colon cancer, while native Africans rarely developed polyps or cancer, O’Keefe designed a study in which a group of African Americans were fed a traditional African high-fibre, low-fat diet, while a corresponding group of low-risk rural Africans changed to a westernised diet. After only two weeks, mucosal biomarkers of colon cancer risk were reduced in the AfricanAmerican group, while increased biomarkers of cancer risk appeared in the Africans.  
What researchers are now coming to understand, is that a westernised diet has a major impact on the composition and activity of the microbiota, causing them to produce metabolites that increase the risk of not only colon cancer but inflammatory bowel disease, cardiovascular disease and diabetes.  
The growing list of “western diseases” potentially linked to the microbiota includes asthma and auto-immune diseases. There is also concern that microbiota, by salvaging excessive nutrients, might actually be contributing to the obesity epidemic.  
Lessons for Africa 
Of course, these conditions are no longer confined to developed countries. As lifestyles change, so does the potential for an explosion of such diseases in Africa. (For instance, obesity is growing fastest in less developed communities.)  
In addition, the microbiome has implications for treatment regimes: some people respond well to drugs for TB or HIV, for example, while others don’t. New evidence suggests this may be due to strikingly different microbiota in individuals – and it may be possible to correct this through dietary means, transplants or other therapies.  
These are the kinds of intriguing issues that the new Institute will be exploring. “We can learn a lot from what was good about the African diet and translate that into what can be useful to prevent westernised diseases occurring in developed South Africa and developed Africa in general,” says O’Keefe.  
The work of the Institute will be strengthened by its unique interdisciplinarity. While housed in the Faculty of Medicine and Health Sciences’ Division of Internal Medicine, it is supported by three faculties – Medicine, Science and Agriscience – and will draw in scientists from various departments and divisions. This will allow researchers to consider the human microbiome in its interactions with the environment, bringing together strands of research on microbiota in the soil, in plants and animals, as well as in the human body.  
“This will give us extra leverage on how to tackle these problems in a novel way,” O’Keefe explains. “The idea is that we form a catalyst for the other disciplines in the university to integrate efforts and get the most out of this exciting new area.”


Olivia Rose-Innes