Microbiome research at IOI
What is a microbiome?
The term ‘microbiome’ refers to a community of microbes, which can involve a combination of bacteria, viruses, fungi and protozoa, co-existing in a defined space. The human microbiome includes trillions of microbes that live in the gut, on the skin and other parts of the body. The world around us contains diverse microbiomes, including those found in animals, soil, water and air.
How do microbiomes relate to antimicrobial resistance?
The majority of microbes in the human microbiome are not necessarily harmful. In fact, many carry out functions that are essential to our health. However, our microbiome can be exposed to antimicrobial drugs, for example, when we take antibiotics, or from the environment around us. Just like how disease-causing bacteria develop the ability to resist the action of these medicines, leading to antimicrobial resistance (AMR), the ‘good’ microbes in our gut can also develop resistance.
Additionally, the microbiomes present in our environment, including in healthcare settings, can carry antibiotic resistance genes, which can be picked up and spread among human microbiomes. Bacteria can pass genes associated with AMR to other bacteria, even from different species in a process called horizontal gene transfer. This means that the more our microbiomes are exposed to antimicrobial drugs and resistant bacteria in the environment, the greater the risk of spreading AMR becomes.
Microbiome research at IOI
The first step to addressing a global health challenge like AMR is understanding the full extent of it. IOI’s Global Surveillance of AMR research programme aims to fill gaps in knowledge of the prevalence and spread of AMR bacteria in low- and middle-income countries (LMICs). IOI has multiple projects that focus on characterising the bacteria present in both human and environmental microbiomes in these hospitals.
Researchers at the IOI are using metagenomics to study microbiomes. Metagenomics is a method that involves analysing all the DNA present in a sample, thus avoiding biases associated with microbiological culture methods.
The IOI works collaboratively with healthcare workers and scientists in hospitals across 13 countries including Nigeria, Bangladesh, and Pakistan. Every step of the research, from initial design to data collection, and finally sample analysis, is led by IOI scientists. This end-to-end approach means that high quality data can be collected and analysed with the ultimate aim of finding solutions to tackle AMR.
Understanding the infant microbiome
Sepsis is a life-threatening body response to infection, often caused by antibiotic-resistant bacteria. It is a leading cause of death in newborns, particularly in LMICs.
But how do newborns become exposed to AMR bacteria within the first few days of life?
To understand this, researchers at the IOI have analysed over 18,000 rectal swabs from newborns and their mothers across 7 countries, to understand the bacterial make-up of their gut bacteria.
They found:
- The carriage of multiple antibiotic resistance genes in both mother and newborn microbiota across all countries.
- Bacteria from mothers and babies were indistinguishable in some cases, suggesting transmission during birth.
- Clusters of similar bacteria in newborns who attended the same hospitals, suggesting environment-to-baby or baby-to-baby transmission of bacteria.
Chinenye Akpulu and Rida Toufiq are DPhil students at the IOI, exploring how babies could be acquiring these genes as soon as they’re born.
“The presence of multiple and different antibiotic resistance genes in newborns within a week of life is striking. We know that some bacteria in the gut carry resistance genes that make infections harder to treat. But we still do not fully understand how babies pick up these resistant bacteria so early in life, or how these resistance genes spread.
“I am researching how factors like birth mode, feeding, environment or antibiotics shape the gut bacteria and resistance in early life in Nigeria. This is especially important because there is very little data from LMICs, where the burden of resistant infections is often highest.”
- Chinenye Akpulu, IOI DPhil student -
Similar research is also being conducted in Pakistan to understand the dynamics of antibiotic resistance genes acquisition, persistence and the factors influencing early in life. This is crucial for improving neonatal health in regions where AMR poses a serious threat, and resources are limited.
"Understanding the development of neonatal microbiomes and resistomes, especially in low- and middle-income countries, is crucial for addressing early-life health challenges and combating the growing threat of antibiotic resistance in vulnerable populations."
- Rida Toufiq, IOI DPhil student -
Polymicrobial wound infections
Wound infections occur when bacteria enter a break in the skin, like a cut or wound, and multiply. They are a major concern in resource-limited hospitals, which may not have enough resources for sanitation, infection prevention and control (IPC) and wound care.
This problem is particularly evident in surgical and orthopaedic wards, where patients often have wounds that require regular care. While it is normal for bacteria to be present in wounds during the healing process, infection-causing and AMR bacteria can also enter wounds in the hospital setting, causing significant delays to wound healing.
Kate Cook is a DPhil student at the IOI studying the bacterial microbiomes of wounds in patients with prolonged infections in an orthopaedic ward in Kano, Nigeria, to understand which species are causing the infections.
“When you take a sample from a wound on a swab and culture it on agar, many bacterial species will grow, including members of the ‘normal’ skin microbiome. To further complicate things, there is increasing evidence that wound infections are generally ‘polymicrobial’, meaning they are caused by more than one species of bacteria, which makes choosing antibiotic treatments difficult.
"Studying the wound microbiome using metagenomics has made it possible to understand which species are causing infections and the AMR genes they carry, as well as how these change throughout a patient’s stay in hospital. Overall, this approach will give us a greater understanding of the extent of polymicrobial infection and of which treatments may be needed in these settings.”
- Kate Cook, IOI DPhil student -
Hospital surface colonisation
Researchers at the IOI have found bacteria carrying antibiotic resistance genes on hospital surfaces in six LMICs. They studied samples from hospital surfaces such as sinks, medical equipment, and ward furniture, and found widespread presence of bacteria carrying antibiotic resistance genes (ARGs), including 18 different bacterial species carrying carbapenemase resistance genes.
Recent research has found similar colonisation of surfaces in modern hospital buildings with antibiotic-resistant bacteria, suggesting this is not an issue limited only to low-resource settings.
The amount and type of bacterial colonisation on hospital surfaces varies significantly between different surfaces suggesting that infection prevention and control (IPC) measures must be specific to each site in order to be effective.
Hear more from our researchers about the importance of tailored IPC regulations.
Researchers are now using metagenomics approaches, where DNA is extracted from the surface swabs to identify all bacterial species in the hospital microbiota. The community of diverse bacteria that colonise different hospital surface types is being profiled according to surface type. With a shotgun metagenomics approach, the presence of ARG and other genetic material present in the hospital microbiome will also be detected.
"Often, the introduction and spread of AMR bacteria in densely populated environments such as hospital wards is complex and multifactorial. These bacterial reservoirs are not just a risk for patients. Family visitors and healthcare workers could also be leaving hospital environments carrying antibiotic-resistant bacteria.
We have found that the hospital microbiota, or the amount and type of bacterial colonisation, varies between hospitals, suggesting infection prevention and control guidelines should be tailored at a hospital level. We hope that our findings will provide valuable evidence to help guide future interventions to control the spread of AMR bacteria in hospitals."
- Maria Nieto-Rosado, IOI DPhil student -
The role of flies in spreading AMR
Insect pests are an often-overlooked part of the collective hospital microbiome, especially in tropical environments which allow pests to thrive in abundance. IOI researchers work with over 30 hospitals across 15 countries, where healthcare professionals collect flies from hospital wards using sticky traps. They ship these samples to Oxford, where IOI researchers analyse the fly microbiome to detect bacteria carrying antimicrobial resistant genes.
The team previously evidenced flies from hospital wards to be carrying diverse bacterial species with antibiotic resistant genes from hospital wards in Nigeria, suggesting the microbiomes of these pests could be acting as a reservoir of AMR.
DNA extracted from flies is now being subject to shotgun metagenomics sequencing to characterise all ARGs in the fly microbiomes from different geographical locations. This technique is more powerful than relying on microbial culture and targeting specific ARGs using PCR, providing researchers with valuable data.
Shonnette is a DPhil student within the IOI, exploring the carriage of a globally prevalent ARG by bacterial species commonly identified as core members of the fly microbiome.
"Flies can be thought of as sentinels of AMR, in that their microbiome is an indicator of the microbes- and their associated ARGs- present in the surrounding environment in which they are found. This is likely to vary depending on the hospital from which flies are sampled and the ARGs circulating within the environment. However, it is interesting to note that certain bacterial species are commonly found, often associated with ARGs, regardless of the location of fly sampling.
"Using techniques such as shotgun metagenomics allows us to get a much better understanding of the total ARGs and the bacterial species carrying them within the fly microbiome than bacterial culture alone can. Such information is essential to furthering our understanding of the role of flies as reservoirs of AMR within hospital settings.”
- Shonnette Premchand-Branker, IOI DPhil student -
"AMR is accelerating at an alarming rate. To confront this threat effectively, we need to understand diverse microbiomes. Otherwise, we risk tackling the problem with a narrow and biased view, often missing the bigger picture.”
- Dr Kirsty Sands, Scientific Lead at IOI -
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