Microbes under the lens

Life on Earth depends on microbes. Without these microorganisms, survival is impossible. They occur everywhere in their billions —- from inside the human body to soil, plants, and oceans.

“It was a microbe that produced oxygen at the start of the world as we know it,” explains internationally renowned microbiome professor Thulani Makhalanyane, who holds a PhD in biotechnology. “Microbes have been our constant companions. To offer three examples: they help our bodies break down important compounds like cellulose in food, which is essential for digestion; in the oceans, they are essential for mitigating climate change as they absorb more than 40% of the carbon dioxide that we produce; and in our soils, microbes help plants to photosynthesise and are essential for soil health and fertility. They are incredibly productive, but there are also those that can be detrimental and make us ill, such as E. coli.”

While advances in genomic sequencing have shed some light on microbes’ precise contribution to life on our planet, very little is known about the composition and function of Africa’s microbial communities in particular.

Fortunately, this knowledge gap is being addressed by Makhalanyane’s novel research on African microbes, including bacteria, fungi, and viruses.

“If we destroy microbiomes, we destroy the basis of life. It’s essential to understand the microbiomes in Africa if we are to promote life-enhancing microbial systems and mitigate against the harmful ones,” he says.

With a P-rating from the National Research Foundation (NRF), Makhalanyane brings a wealth of experience to Stellenbosch University (SU), which he joined in November 2023. (P-rated researchers are recognised for having the potential to become global leaders in their field on the basis of their doctoral and/or early postdoctoral career outputs.)

He holds a joint position in the Department of Microbiology and the School for Data Science and Computational Thinking. He also works closely with the Centre for Epidemic Response and Innovation (CERI), which is currently expanding its microbiome research. Prior to joining SU, he worked in the Department of Genetics at the University of Pretoria as the holder of the DSI/NRF SARChI Chair in Marine Microbiomics.

Microbiomes in the soil and water

Makhalanyane says it is a very exciting period for the study of African microbiomes and for African genomics research. “The University recently invested in the Biomedical Research Institute (BMRI) — a phenomenal facility on the Tygerberg campus with the largest genomic sequencing ability on the African continent. Whereas we previously had to do most of the sequencing abroad, we can now do it at a high scale right here. There are so many different aspects of genomics and microbiome research and our African Microbiome Group at SU, which includes 18 researchers, is using high-throughput sequencing to study terrestrial, marine, and freshwater microbiomes, as well as microbiomes in the human body.”

With regard to soil, he says relevant studies have shown that microbial communities drive nutrient recycling and the decomposition of organic matter, both of which are essential to soil health. When farmers add nitrogen-rich fertiliser to their land year after year, it destroys the natural microbiome balance and the soil ultimately becomes infertile. As such, there is a worldwide movement towards using regenerative agriculture to restore soil health. To assist in this process, farmers can spray batches of different isolated microbes onto the soil surface to repopulate the microbiomes, thereby regenerating soil and plant health.

Makhalanyane’s research on environmental microbiomes has developed through his long-term work on understanding the ecology of microbial communities in extreme environments, notably the Antarctic, the Namib Desert, and the Southern Ocean. “Extreme environments have a lower number of microbes present, which allows us to gain mechanistic insights,” he explains. “In more complex environments, there are literally billions of microbes and what adds to the complexity is that they are constantly changing and exchanging genes.

“We have several studies on marine ecosystems that illustrate this,” he adds. “Certain microbes rapidly adapt to any kind of change. For example, a selection of microbes can break down microplastic contamination. If we see a transition to higher proportions of these microbes, then we know there is a high density of microplastics present in that part of the ocean.

“We also look at the impact of other human activities on marine systems through the ecological surveillance of microbiomes in estuaries, where river and sea waters meet. Our samples can reveal, for example, the presence of cyanobacterial blooms and other bacteria. We use this to alert people and inform policy so that management decisions about river toxicity and pollution control can be made at source.”

The human body as host

With regard to research on microbiomes in the human body, Makhalanyane explains that predominantly carbohydrate- or fast-food-based diets have been shown to adversely affect microbial behaviour in the gut and potentially lead to disorders such as leaky gut. “Researchers in our African Microbiome Group have studied the human gut microbiome in both rural and urban South African adults in Venda and Pretoria,” he says. “People in rural areas tend to have far higher microbial diversity in their systems because their diets are higher in fibre, compared to people in urban areas whose diets tend to be high in carbohydrates and fast foods.

“A carbohydrate-rich diet stops the microbes from crossing the mucosal [intestinal] barrier in the gut. The microbes might then start feeding on the mucosal area, causing leaky gut, which is a product of an unbalanced diet. Changing to a healthy, high-fibre diet in which the microbes feed on fibre is essential for good health. Several other studies have linked imbalanced microbiomes to the development of cancer, diabetes, and endocrine disorders.”

At the same time, Makhalanyane says that, as researchers, they are careful not to generalise — every person’s gut microbiome is unique and linked to their specific genetics and diet. What might be good for one person might not be good for another. The health of microbiomes also depends on the interaction between the microbes, he explains. There are microbiomes that exhibit high levels of cooperation and there are disjointed microbes that are unable to cooperate with each other, rendering the host person susceptible to disease-causing pathogens.

Probiotics are often prescribed to restore microbial health when, for example, taking a course of antibiotics. However, Makhalanyane says that while there is some evidence to show that probiotics help in the short term, they don’t have long-term impact. “Probiotics tend to consist of one microbe, but in a biological system microbes depend on interaction with each other. So, it might bring short-term relief but not long-term relief. This is because you aren’t adding consortia of microbes that cooperate.”

Collaborating for research impact

Given the transdisciplinary nature of microbiome research, the African Microbiome Group works in a wide range of fields. One of their ongoing, long-term studies focuses on children born to HIV-positive mothers receiving antiretroviral drugs. Conducted in collaboration with the University of Pretoria, the Siyakhula Trial has, for the past ten years, involved studying the microbiomes in the stools of these children. “It is all about long-term intervention, with a focus on nutrition,” Makhalanyane says.

“Long-term trials show that even if children are born HIV negative, they can still show stunting, and that this is related to the microbial composition of their systems and to their ability to digest certain metabolites such as short-chain fatty acids, which affect their digestion. Altering their diet by increasing high-fibre foods that promote digestion has a positive impact on their growth.”

Another ongoing microbiome study — a collaboration between researchers in the African Microbiome Group and Prof Ronelle Burger from the Department of Economics at SU —- set out to quantify the benefits, in terms of human health, of moving from informal housing to Reconstruction and Development Programme (RDP) housing. “We research the microbial environment, the air and water quality, the presence of waste and other factors,” says Makhalanyane. They also sample the stools of pregnant women to quantify cases of illness before and after a move to RDP housing. Makhalanyane and his team have been able to use this data to show the benefits of RDP housing to both human health and state healthcare costs.

“These are just a few of the African Microbiome Group’s research projects and we’re very excited about the contribution our research can make to addressing several of the United Nations’ sustainable development goals,” Makhalanyane concludes.