Among us, another world exists. With floating particles suspended in mid-air and inhabitants with a life of their own, invisible to the naked eye—their traces extending from the environment outside to our homes, and even within our body.

They lay hidden until the tools to study their effects on our health came along. But now it has become clear that small as they are, their impact on health is not to be confused with their size.

“When you look at population health, we know that there are individual risk factors for certain diseases, such as smoking, diabetes and high blood pressure, which may not be present in the majority of the population,” said Adjunct Assistant Professor Joel Aik from Duke-NUS’ Pre-Hospital & Emergency Research Centre (PERC).

"But when it comes to something in the environment like air pollution or weather variations, that tends to impact the entire population. We can’t avoid breathing the air around us, that is why we need to study the impact on our health so appropriate measures can be taken."

Adj Asst Prof Joel Aik

 
“But when it comes to something in the environment like air pollution or weather variations, that tends to impact the entire population. We can’t avoid breathing the air around us, that is why we need to study the impact on our health so appropriate measures can be taken,” added Aik, who is also a principal research scientist at the National Environment Agency (NEA). 

 
A breath of fresh air?

It may not seem or smell like it, but the air we breathe is actually a complex mix comprising a multitude of substances—good and bad ones. One of the main pollutants is fine particulate matter (PM), each of which is but a thousandth of a millimetre. These particles come from a range of sources, from vehicles plying the roads to emissions from factories. All of them are bad for us and most are produced as a result of human activities.

“If you think about a strand of hair and compare that with the size of a PM2.5 particle, it would be approximately 25 times smaller than a strand of hair,” said Aik.

“The particles are so small, they can reach into the innermost section of your lungs and be absorbed into your bloodstream,” he added. When that happens, they accumulate as plaques within the arteries, adding on to the existing burden of plaques in the body from other sources.

When these plaques rupture, chaos ensues.

“Your red blood cells rush in to stop the bleeding by forming clots. But because of that, it reduces the width of your arteries causing less blood flow to where it should go. When there is a reduction in oxygen to your heart or your brain, it can cause all kinds of health problems,” said Aik.

And when unwanted hitchhikers seize the opportunity for a ride, they create more issues when inhaled. Like microorganisms capable of causing diseases, and even allergens.

“For example, on the days when we have haze here, it is not only the particles themselves that can cause difficulty with breathing, but for people who have allergies, they tend to have a more risky day as common allergens can piggy back on these particles and make their way deep into the lungs,” explained immunologist Ashley St John, an associate professor with Duke-NUS’ Emerging Infectious Diseases Programme, in this issue’s podcast on allergies.   

 
Honing in on the dangers

Concerned about the health risks posed by these pollutants in the air, Aik, an environmental epidemiologist, has spent the last 12 years studying the effects of air pollution on population health, analysing data from as early as the days of the 2009 South-East Asian haze. He found that higher levels of PM2.5 and PM10 (particles that are ten microns in size) were linked to high levels of acute conjunctivitis in Singapore.

Then in a recent study, Aik and his team together with PERC colleague, Professor Marcus Ong, discovered an association between higher levels of PM2.5 particles with an increase in the risk of out of hospital cardiac arrests. He had observed the same worrying trend in another earlier study investigating the effects of air pollutant exposure on the risks of stroke.

“So we know that high levels of air pollutants potentially influence cardiovascular outcomes,” he added.

With the risks that come with exposure to pollutants outdoors, it might seem intuitive to stay indoors, in the comfort of an air-conditioned room.

But that might not always be a good idea.  

Since most of the air is taken from outside the building before it is chilled, this means that the air quality indoors is dependent on that outdoors. Moreover, for a building to remain cool and comfortable without incurring larger energy bills, explained Aik, the cool air has to be prevented from escaping, which reduces the amount of ventilation within a space.

But it is not just air quality that impacts health. “The range of environmental factors that can affect population health is actually quite wide and diverse,” added Aik, whose other research interest is in studying the effects of climate variability on health.

“And the biting frequency of the Aedes mosquito will be higher when it’s hotter, too,” he added. 

 
 
Making sense of another hidden community

Apart from lurking in vectors like mosquitoes, viruses abound in our environment. Along with a host of other organisms on the micro-scale, they make up the microbiome—a diverse population of organisms including bacteria, viruses and fungi.

They are found everywhere around us, on our body and even within.

“The biggest interest amongst the many microbiomes has been in the gut microbiome, largely because it consists of the most complex types of organisms in both diversity as well as the absolute amount,” said Professor Jeremy Lim from the Saw Swee Hock School of Public Health.

Advances in technology have enabled researchers like Lim to study the composition of microbes in the gut.  By sequencing their genetic material, he can profile an individual’s microbiome. “Genetically, all of us are 99.9 per cent identical, but from a microbial point of view, we are only about 20 to 30 per cent similar,” he added.

These differences, according to Lim, can affect how someone responds to a certain drug or serve as an indicator of a person’s risk of developing a particular disease.

“It’s just a matter of time before this then diffuses into clinical practice and changes how we prescribe drugs and think about precision medicine or health,” he said. “So we can say you have a certain microbiome profile that predisposes you to certain diseases. But instead of changing your life, we ask you to change your microbiome.”

What we do matters

Citing studies that have shown how symptoms of conditions such as attention deficit hyperactivity disorder have been improved by changing the microbiome, Lim said, “We are realising that because of the microbiome, many of the non-communicable diseases have an infectious or a microbial link.”

He found that it only takes about five days to start transforming a person’s microbiome by changing their diet. “Every time we eat, we feed ourselves, but we also feed our microbes. Certain species will utilise specific nutrients better than others and grow faster, crowding out the species that don’t use these nutrients. That’s also why our microbiome has so much inter-individual variability,” said Lim.

Maintaining these beneficial changes is important stresses Lim. “Our microbiome tends towards homeostasis, meaning there is a tendency for the system to go back to its original state,” he said.

Another thing to avoid is the unnecessary use of antibiotics, reserving these drugs for when they are truly needed. “The science is very, very compelling that antibiotics harm the microbiome,” added Lim.

And it is not just the gut microbiome that is affected.

When waste products containing antibiotics consumed by individuals or used on farms are released into the environment, they create a selection pressure.

“The bacteria will try to fight back as a means of self-preservation. They are quite efficient and can mutate faster compared to complicated organisms. So within a day, hundreds of generations of bacteria are produced,” said Duke-NUS Emerging Infectious Diseases Associate Professor Andrea Kwa.   

All it takes is for some bacterial cells with mutations that make them resistant to survive in an environment with antibiotics. To make matters worse, since bacteria can confer antibiotic resistance to one another through transferring genetic material, there is no telling when the next superbug—that is virtually resistant to all antibiotics—will emerge.

When there are more antibiotic-resistant bacteria out there, the chances of someone catching such a bug also increases. Without a means to fight these bacteria, the resulting infections can be deadly, if they cannot be controlled and eradicated.

 
Fighting for a better future with data

Having seen patients with superbug infections waste away after even the antibiotics of last resort fail, Kwa is determined to help others avert the same fate.

For that to be possible, she needs to understand these invisible foes. That’s why she has been keeping a database of multidrug-resistant bacteria. 

We cannot stop because we always find a new pathogen every year.”

 Associate Prof Andrea Kwa

“We cannot stop because we always find a new pathogen every year,” said Kwa, who is also the Assistant Director of Pharmacy (Research) at the Singapore General Hospital (SGH). 

Kwa is not the only one who hopes to bring about change with data.

When Lim realised that the microbiome research from other countries such as America or Europe could not be applied blindly to the local context, he and his colleagues set about collecting data from individuals in Asia. “It was inappropriate for us to simply take the science from countries where the diet, the lifestyle and living conditions are very different and wholesale transplant them into Asia,” said Lim.

“For these reasons, we said, Asia needs our own database, our own research and our own discoveries. And that’s why we set up AMiLi which is a portmanteau of three words: ‘Asia’, ‘Microbiome’ and ‘Library’ in 2019 .” 

Prof Jeremy Lim

 

Professor Jeremy Lim (left) with Duke Professor John Rawls (first from right) at AMiLi. In 2019, Lim set up his team at AMiLi with the aim of creating Asia’s own gut microbiome database// Credit: Jeremy Lim

Today, AMiLi has the largest multi-ethnic Asian gut microbiome database, and is Southeast Asia’s first gut microbiome transplant bank. Using the data from the microbiome database, Lim’s team is looking at ways in which the information gleaned can be used to improve human health.  

Aik too, sees the value in collecting and analysing data that is specific to the region.

Referring to the new set of air quality standards released by the WHO for member states, he said: “The evidence supporting these thresholds are based on studies that have been conducted elsewhere. Whether or not these studies are applicable to Singapore, we actually do not know.”

“Some studies have reported adverse health outcomes at air quality levels lower than what has been prescribed by the WHO. So that’s why I think it’s important for Singapore to generate its own evidence and then for us to set our own country-specific goals.”

The findings could be used to support and inform initiatives like “The Singapore Green Plan 2030”, a national movement focused on sustainable development for maximum impact. One of the key targets under the Green Plan includes having more cleaner-energy vehicles on the roads, which Aik says would help reduce a major source of PM2.5 in the air.

“We hope to see a progressive reduction in adverse health outcomes related to PM2.5, perhaps in the mid-2030s, or closer to 2040,” added Aik, who is hopeful that we will stop judging these particles’ impact by their size.

“Ultimately what we want to do as researchers is to influence policy and practice.”  

Adj Asst Prof Joel Aik