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28 May 2021

HKUMed discovers a causal link among food allergies, gut microbiota development in infancy, birth methods and mother’s ethnicity

PRESS RELEASE

Researchers from HKU-Pasteur Research Pole (HKU-PRP) at the School of Public Health, LKS Faculty of Medicine of The University of Hong Kong (HKUMed), in collaboration with their Canadian collaborators, discovered for the first time a causal link between caesarean section birth, delayed gut microbiota development (persistently low Bacteroides, high Proteobacteria and colonised with Clostridium difficile) and peanut sensitivity in infants. In addition, the effect is also found to be almost four times as more pronounced in children of Asian descent than others. The findings are now published in Gastroenterology, a leading peer-reviewed medical journal. [link to the publication].

Research methods and findings

The research team characterised the composition of gut microbiota at three or four months of age and again at one year, using next-generation sequencing (a massively parallel sequencing technology used to determine the order of nucleotides in DNA). They identified four typical trajectories for bacterial development, including one in which the infants had persistently low levels of Bacteroides. It is a type of bacteria known to be critical to immune system development perhaps through the production of sphingolipids, the key to cell development and signalling. This profile was most common in babies born by caesarean section. ‘In general, the level of Bacteroides should increase with age until it becomes adult microbiome. It is an indicator for maturation of gut microbiome in children,’ said Dr Hein M Tun, Assistant Professor of HKU-PRP of School of Public Health, HKUMed.

The infants were given skin prick tests at one and three years of age to assess their reaction to a variety of allergens, including egg, milk, soy and peanut. The babies with low Bacteroides levels were found to have a threefold increase in their risk of developing a peanut sensitivity by aged three — and the risk was eight times higher for babies born to mothers of Asian descent. In the study, 12% of children are born to Asian mothers, mainly Chinese (41.5%), and they have a higher prevalence of peanut sensitisation than Caucasian children (9.4% vs 2.4%).

The team did further mediation analysis to look for causal effects between Asian ethnicity and peanut sensitisation. ‘The analysis provided additional evidence for the causal association with early gut microbiota development that links to caesarean section,’ said Dr Tun, noting it is the first study to identify this link. 

Research significance

Despite the relatively low percentage of food allergies among children in Asia, such as Mainland China (more than 6% of children under the age of five)1 and Hong Kong (5-8%)2, the latest HKUMed findings echoed with those of previous studies that Asian children born in Western countries, including Australia, have higher rates of peanut allergy than those born in Asia3.

A multitude of pre-, peri and post-natal factors, including changes in diet, microbial exposure and environment could be the reasons behind. Increasing evidence supports the role of early-life gut microbiota in developing allergic diseases, however, ecological changes of gut microbiota during infancy in relation to, as well as its interaction with host factors in food sensitisation, remain unclear.

‘As the gut microbiota are developing in infancy so is the gut’s immune system, training the gut to react to pathogens and to be tolerant of the food that we require,’ explained Dr Tun. ‘Several factors influence microbial seeding and colonisation in early-life, mainly the method of birth, breastfeeding, exposure to antibiotics and chemical disinfectants, and having siblings and furry pets.’

The best path is to avoid caesarean birth unless it is medically necessary. Asian parents especially those living in Western countries should pay extra attention to the risk of developing Western allergic phenotypes among their children, and they are advised to keep traditional diets, avoid overuse of disinfectants, and keep furry pets. ‘According to the hygiene hypothesis, overly clean environment will hamper the development of children’s immune system and they should expose to more diverse microbes in their first three years of life to prevent from allergic diseases and asthma,’ added Dr Tun.  

[1] Renz H, Allen KJ, Sicherer SH, et al. Food allergy. Nat Rev Dis Primers 2018;4:17098.

[2] Society THKA. Pathology and Causes of Food Allergy, 2015.

[3] Wang Y, Allen KJ, Suaini NHA, et al. Asian children living in Australia have a different profile of allergy and anaphylaxis than Australian-born children: A State-wide survey. Clinical & Experimental Allergy 2018;48:1317-1324.

 

About the research team

The research was conducted by a team led by Dr Hein M Tun, Assistant Professor, HKU-PRP, School of Public Health, HKUMed. The other member of the research team from HKU-PRP was Mr Ye Peng, PhD student. Investigators from the Canadian Healthy Infant Longitudinal Development (CHILD) study were Dr Anita L Kozyrskyj, Dr Bolin Chen, Mr Theodore B Konya, Dr Nadia P Morales-Lizcano, Dr Radha Chari, Dr Catherine J Field, Dr David S Guttman, Dr Allan B Becker, Dr Piush J Mandhane, Dr Theo J Moraes, Dr Malcolm R Sears, Dr Stuart E Turvey, Dr Padmaja Subbarao, Dr Elinor Simons and Dr James A Scott.

Acknowledgements
This research was specifically funded by grant 227312 from the Canadian Institutes of Health Research Canadian Microbiome Initiative (Dr Anita L Kozyrskyj). The Canadian Institutes of Health Research and the Allergy, Genes, and Environment (AllerGen) Network of Centres of Excellence provided core support for the CHILD study. Dr Tun was funded through a Canadian Institutes of Health Research Fellowship and an Alberta Innovates Postdoctoral Fellowship in Health.

About HKU-Pasteur Research Pole
HKU-Pasteur Research Pole (HKU-PRP) is a joint laboratory of HKU and Institut Pasteur, established in 2000 with the aim to developing programmes of excellence in research and education that will generate biological knowledge and advance the understanding and treatment of infectious diseases.  HKU-PRP benefits from the outstanding scientific environment offered by the School of Public Health, HKUMed, with its significant contributions, both locally and internationally, to research on emerging viral diseases and improving health.  Moreover, HKU-PRP is part of the IP International Network, a unique model for health cooperation to further science, medicine and public health with more than 100 years of history.

http://www.hkupasteur.hku.hk/ 

Researchers from HKU-Pasteur Research Pole (HKU-PRP) at the School of Public Health, LKS Faculty of Medicine of The University of Hong Kong (HKUMed), in collaboration with their Canadian collaborators, discovered for the first time a causal link between caesarean section birth, delayed gut microbiota development (persistently low Bacteroides, high Proteobacteria and colonised with Clostridium difficile) and peanut sensitivity in infants. The effect is also found to be almost four times as more pronounced in children of Asian descent than others. From left: Dr Hein M Tun, Assistant Professor, HKU-PRP, School of Public Health, HKUMed and Mr Peng Ye, PhD student.

 

Media enquiries

LKS Faculty of Medicine, HKU

Email: medmedia@hku.hk

Download the Press Release (English).

Download the Press Release (Chinese).

11 May 2021

First Participants Vaccinated In HKU Trial To Test COVID-19 Vaccines In Healthy Adolescents

PRESS RELEASE
 
Investigators of the Department of Paediatrics and Adolescent Medicine and the School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, are now launching the COVID-19 Vaccination in Adolescents (COVA) study. 300 healthy adolescents aged 11 years or above and their parents will be offered one of the COVID-19 vaccines available in Hong Kong of their choosing. The reactogenicity and immunogenicity profile of the vaccines will be compared. The first participants have just received dose 1 of their Fosun Pharma/BioNTech BNT162b2 vaccine.
 
The COVID-19 pandemic has caused more than 100 million cases and 3 million deaths globally, and over 10,000 cases in Hong Kong. The virus may cause long COVID and multisystem inflammatory syndrome in children. Some emerging virus variants have also been found to be more infectious to teenagers. Children and adolescents under 20 years old are contagious, and infected children may spread the virus to their grandparents. The prolonged suspension of classes and social distancing have also had a negative impact on students. Therefore, children and adolescents urgently need to be immunized against COVID-19.
 
COVA will recruit 300 healthy adolescents aged 11 years or above and their parents. At the moment, the families will be offered to receive the BioNTech/Fosun BNT162b2 or SinoVac's CoronaVac. Each family can freely choose the vaccine they receive, given each family member receives the same vaccine. Participants will report adverse reactions and other adverse events following immunization, and be followed up for immunogenicity assessments and vaccine breakthrough COVID-19 over a period of 3 years. Participants are covered by the Hong Kong government’s COVID-19 vaccine indemnity fund. Recruitment is ongoing, and those interested may sign up at https://paed.hku.hk/registration/cova/ or call or WhatsApp the Department of Paediatrics and Adolescent Medicine at 5944 5961 for more details. 
 
Timely local data on the reactogenicity and immunogenicity of COVID-19 vaccines in adolescents will inform the public and the government whether the vaccines should be given to adolescents, and allow complete school reopening as soon as possible.
 
About the research team
The COVA investigators include Professor Yu-Lung Lau, Doris Zimmern Professor in Community Child Health, Chair Professor of Paediatrics, Department of Paediatrics and Adolescent Medicine, HKUMed, Professor Malik Peiris, Tam Wah Ching Professor in Medical Science, Chair Professor of Virology, Centre for Immunology & Infection, Institut Pasteur and School of Public Health, HKUMed, Professor Wing-hang Leung, Head of Department and Clinical Professor, Department of Paediatrics and Adolescent Medicine, HKUMed, Professor Wenwei Tu, Antony and Nina Chan Professor in Paediatric Immunology and Professor, Department of Paediatrics and Adolescent Medicine, HKUMed, Professor Roberto Bruzzone, Visiting Professor, School of Public Health, Centre for Immunology & Infection, HKUMed, Professor Leo Poon, Professor, School of Public Health, HKUMed; also from the Department of Paediatrics and Adolescent Medicine, HKUMed: Dr Patrick Ip, Clinical Associate Professor, Dr Pamela Lee Pui-Wah, Clinical Associate Professor, Dr Jaime Rosa Duque, Clinical Assistant Professor, Dr Gilbert T Chua, Clinical Assistant Professor, Dr Wilfred Hing-sang Wong, Senior IT Manager, Ms Sau Man Chan, Research Nurse, Dr Kai N Cheong, Honorary Clinical Assistant Professor, and Mr Daniel Leung, MBBS/PhD student.
 
About the Department of Paediatrics and Adolescent Medicine, HKU 
The Department of Paediatrics and Adolescent Medicine is a pre-eminent international paediatrics department in Asia striving for the health and well-being of children and youth. We endeavour to provide high-quality children-centred health care services to the community; produce graduates, postgraduates and paediatricians of distinction, committed to lifelong learning, integrity and professionalism; engage in both basic and clinical research of innovation and high-impact, within and across disciplines; and form alliances and partnerships in order to achieve our vision and mission. 
 
About the Centre for Immunology & Infection (C2i)
The C2i is the fruit of a long-standing partnership of more than 20 years between the LKS Faculty of Medicine of the University of Hong Kong (HKUMed) and the Institut Pasteur, two major institutions combining their expertise to establish this centre of excellence. C2i, adopts innovative strategies to identify and contain emerging infectious diseases and transform Hong Kong and the Greater Bay Area into a global hub of knowledge and research.
 
The Centre for Immunology & Infection's work is centered around four major research programs to face public health challenges and make Hong Kong a global center of excellence for precision medicine population strategies and innovative interventions targeting emerging infectious diseases. They aim to characterise immune responses to infectious agents and their components in a healthy Asian population and develop new vaccine platforms for influenza, new strategies for mosquito-borne viruses and new treatments for lethal respiratory virus infections. The C2i is led by Professor Malik Peiris (Managing Director) and Professor Roberto Bruzzone (Co-director).
 
The study is funded by the Food and Health Bureau and private donations.
 
Media enquiries
Department of Paediatrics and Adolescent Medicine, HKU
Daniel Leung (Tel: 2255 4538 | Email: dan.leung@hku.hk)
 
 

Photo of COVA study team in the community vaccination centre on May 8 2021. The COVA
study is supported by experienced paediatricians, nursing staff, clinical research assistants
and medical students at the vaccination centre.