Unravelling the Role of Gut Microbiome in the Immune System
From the food a person eats to whether they had a pet in childhood and how much time they spend in nature, a myriad of factors can affect the trillions of microorganisms in the gut.
And now research on gut microbiome, the microorganisms living in the human digestive tract, by Dr Hein M Tun, Assistant Professor, HKU-Pasteur Research Pole at the School of Public Health, HKUMed, has discovered a causal link between caesarean section births and peanut allergies.
His study found that babies born via caesarean section had persistently low levels of Bacteroides, a group of bacteria Dr Tun describes as “keystone” bacteria for the gut. This type of bacteria is known to be critical for the development of the immune system.
Infants with low levels of this type of bacteria had a threefold risk of developing a peanut sensitivity by age three, the study found. The risk of developing a peanut allergy was eight times higher for children born to mothers of Asian descent.
Food allergies are comparatively rare in Asia, with 5 to 8 per cent of children in Hong Kong found to have food sensitivities. However, other studies have found that Asian children born in Western countries have higher rates of peanut allergies than those born in Asia.
Dr Tun trained as a public health veterinarian in Myanmar before continuing his education with a PhD in molecular biology at the University of Hong Kong.
He first studied the roles of infant gut microbiome in health and diseases as a post-doctoral researcher at the University of Alberta, using data from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. This database, which contains more than 500,000 biosamples, was used for the study into allergic sensitisation and childhood obesity.
A second immune organ
The trillions of bacteria, viruses, fungi and other microorganisms living in the human digestive tract are known as gut microbiota. These microorganisms are crucial for human health but they can be altered by diet, environmental factors or drugs, such as antibiotics.
Gut microbiome science has grown since 2010 when next generation sequencing became available allowing researchers to characterise the bacteria in the gut, Dr Tun said. And research over the past decade has highlighted the role of gut microbiome in the immune system.
“People think the immune system is only [controlled by] the body, but it is orchestrated by our microbiome,” Dr Tun said.
“Our gut microbiome is what we call a second immune organ. Our microbiome stimulates our immune system to produce different types of immunity,” he added.
Despite fecal transplants — transferring fecal bacteria from a healthy person into another individual — appearing in historical records of Chinese medicine, gut microbiome science is in its early stages in Asia compared to the US and Europe, Dr Tun said.
The general public in Asia believes that all bacteria is bad, when there is in fact both good and bad bacteria, Dr Tun said.
Dr Tun said researchers are now working to understand what constitutes “healthy” gut microbiome as there is currently no concrete definition. And mapping early life microbiome is crucial to this effort, he explained.
Gut microbiome in infants
There are two theories on where a child’s microbiome originates, Dr Tun said. One is that microorganisms travel from the mother through the placenta, however this is not well proven. The second is that the first colonisation happens at birth through the vaginal canal, which exposes a baby to the mother’s microbiome. A caesarean section skips this exposure.
Studies have found that the gut microbiome of babies born by vaginal birth is similar to that of their mother, while if they were born by caesarean it bears more similarity to skin microbiome.
“Your immune system develops mostly in early life together with microbiome development. That cannot be easily changed after you grow up… so that is also affecting lifelong health and disease,” he said.
Dr Tun envisions adapting health policies to include early testing of a child’s microbiome to ensure the presence of this “keystone” bacteria. Infants with low levels of Bacteroides could be given microbiota-based interventions to supplement this bacteria, much like a childhood immunisation programme.
The COVID-19 effect
The influence of lifestyle changes and their effects on gut microbiome have been highlighted by the COVID-19 health crisis.
The pandemic has led to an increased use of cleaning products and mask wearing which has meant humans are exposed to fewer bacteria in their daily lives, resulting in changes to gut microbiome.
A study by Dr Tun was the first to show changes to the gut microbiome since the outbreak of the virus. His research showed an increase in opportunistic pathogens and a reduction in good bacteria as well as an increase in resistant genes to chemicals found in face masks and takeaway containers.
However, the long-term effects of the pandemic on our microbiome are yet to be established.
“In the study we cannot see the impact yet, we only see the changes,” he said. “But the changes are not good because we think some of the changes are increasing anti-microbial resistant genes, increasing opportunistic pathogens, it’s not desirable. These chemical resistant genes are also not desirable.”
“We are fighting COVID-19, our enemy, but at the same time we are losing our friends that are beneficial to our bodies,” he said.
The pandemic has also provided other avenues for the research of gut microbiota. Dr Tun’s team recently undertook a study of gut microbiome and COVID-19 vaccines to examine if the gut microbiota modulate the antibody response to vaccines.
“Our microbiome is playing a significant role in immune modulation for vaccination,” he said. “Our objective is trying to understand in this COVID-19 context, what kind of microbiota is essential for our body in order to achieve the optimum immune response against vaccination.”
The study, which measured participants’ antibody levels and the composition of their gut microbiota found the efficacy of Sinovac and BioNTech vaccines correlated to the level of Bifidobacterium adolescentis. Those who did not have this bacteria had a lower antibody response to Sinovac, while those who took the BioNTech vaccine and lacked this and a second bacterium had lower antibody responses.
Dr Tun envisions the supplementation of this beneficial microbe could complement the global vaccination drive by optimising the body’s immune response.
