New laboratory aims to expand microbiome research in Africa

A new laboratory opened at the University of Cape Town to accelerate research on microbiomes in Africa. A human’s microbiome includes trillions of microorganisms that live in and on the body and there’s compelling evidence linking disruptions in the balance of bacteria to human health — including someone’s risk of contracting diseases. And while there’s vast diversity in microbiomes across the African continent, it’s significantly underrepresented in global research and databases — much of the research has been from the United States and Europe, said professor Jo-Ann Passmore, lead of the Vaginal Microbiome Research Consortium for Africa. This new effort, called the Microbial Interactions Laboratory, has brought together seven research teams studying different elements of the human microbiome. They’re exploring the lung microbiome’s link to acquiring pneumonia and tuberculosis; the vaginal microbiome’s link to a woman becoming infected with HIV and experiencing adverse birth outcomes; and the gut microbiome’s link with common gastrointestinal disorders like bowel disease, as well as neurological disorders including autism and depression. And the ways the gut microbiome impacts the body’s metabolism of medicines. There will also be efforts to set up an African biobank to facilitate local fecal microbiome transplants, which can help establish healthy bacteria in lower intestines, and a vaginal biobank to facilitate local whole vaginal microbiome transplants for women in Africa. They’re working to better understand the interplay between a person’s genetics, pathogens, and inflammation in the body to help foster the development of microbiome-centered health solutions for the continent, including diagnostics and treatments. “It's shifting the dynamic to make much more data available that is locally led,” Passmore said. A microbiome network The new Microbial Interactions Laboratory is hosted and funded by the University of Cape Town’s Institute of Infectious Disease and Molecular Medicine, or IDM, with infrastructure support coming from national funding. Wellcome’s Centre for Infectious Diseases Research in Africa, or CIDRI-Africa, donated major equipment to the lab and it received funds from the Gates Foundation to facilitate studies. Passmore said the differentiating factor of the lab is it goes beyond documenting diversity of bacteria existing in microbiomes to how these organisms interact with each other and how this impacts health. A person’s microbiome is impacted by where they live, with factors such as the climate, local diets, human genetic diversity, water quality, antibiotic use, and hygiene practices. “All of those factors would drive the indigenous microbiomes in a woman from Cape Town versus a woman from Kenya, for instance,” Passmore said. And microbiomes vary within countries. For example, reproductive health teams at IDM have done studies in Cape Town and Johannesburg where they've found that women living in these two cities have different bacteria colonizing their vaginal microbiomes. Passmore said this new laboratory stands on the shoulders of important continental initiatives such as the Human Heredity and Health in Africa, or H3A, initiative and H3ABioNet — which has invested heavily in bioinformatics infrastructure. With the Microbial Interactions Laboratory, researchers are working to create a network of players in the microbiome field in South Africa, such as University of the Witwatersrand, University of KwaZulu-Natal’s Centre for the AIDS Programme of Research in South Africa, and Stellenbosch University and its Centre for Epidemic Response and Innovation, which has sophisticated genomic sequencing capacity — which is necessary in mapping microbiomes and identifying African bacterial strains. And they’re working to create a broader network of researchers across the continent, Passmore said. The vaginal tract One area of focus is female reproductive health. “There's a lot of data on gut compared to vaginal microbiomes, but the contribution of Africa to vaginal microbiomes is even more limited,” Passmore said. And the reproductive tract is quite different from the gut, she said. While it's beneficial for the gut to have diverse microorganisms, a healthy vaginal tract is dominated by a single strain of microorganisms called lactobacillus, she said. Much of Passmore’s work focuses on bacterial vaginosis — a disruption in the vagina's natural bacteria, with an overgrowth of problematic bacteria. Bacterial vaginosis isn’t sexually transmitted but can result from condomless sex, vaginal douching, certain hormonal contraceptive use, and hormone changes during menstrual cycles — and it’s frequently asymptomatic, Passmore said. It's a major driver of genital inflammation, which leads to increased risk of contracting HIV. Inflammation brings in cells from the immune system to the vagina that HIV can infect and also causes microtears in tissue that make it easier for HIV to penetrate deeper tissues, Passmore said. Without that inflammation, the body’s mucosa — soft wet tissues lining the reproductive tract — is generally good at providing protection against contracting the virus, she said. “If we can treat the cause of the inflammation, we can lower HIV risk in South Africa,” Passmore said. Bacterial vaginosis can make a woman more likely to contract human papillomavirus infection, or HPV, which can lead to cervical cancer. It can also impact fertility and whether babies are born preterm. An inflamed reproductive tract isn’t conducive to implantation and can cause scarring of the tissue that embryo implantation needs. And in pregnancy, contractions and delivery are typically triggered by inflammatory processes, so having high inflammation can fool the body to start contractions. Microbes can also move into the uterus and cause infections in developing fetuses, she said. “It's like this invisible inflammatory condition that increases risk,” Passmore said. The beneficial lactobacilli in the vagina are able to fight off problematic bacteria and create an acidic environment in which these unwanted bacteria don’t thrive. Passmore and her teams are exploring whether local, beneficial vaginal bacteria are better able to suppress the growth of problematic bacteria for South African women than lactobacillus found in the United States. She called this concept evidence of “evolutionary co-adaptation” between beneficial and harmful bacteria existing in the same geographies. “That's the kind of science that will transform decisions around whether geography matters and how strains are selected,” Passmore said. A doctor’s go-to treatment for bacterial vaginosis is often the antibiotic metronidazole — but its overuse and inappropriate use is fueling emerging resistance of bacteria to this drug. Many women that use antibiotics for bacterial vaginosis get a recurrence of the condition within six months after treatment, Passmore said. The antibiotic removes harmful bacteria but also does nothing to ensure beneficial bacteria that are also removed grow back in stronger numbers. She compared the vaginal microbiome to a grassy lawn, where the grass represents lactobacillus and bacterial vaginosis is akin to weeds. “It’s like the weeds just popping up everywhere and taking over the grass,” Passmore said. Antibiotics are the weed killer, but a live biotherapeutic is needed to re-seed the grass to restore a stable community of beneficial bacteria. And ideally, researchers will ultimately develop a seeding strategy that doesn’t require a woman to use antibiotics at all.