An international study led by scientists in Singapore finds that bacteria previously thought to be harmless can worsen existing lung disease.
A team of international scientists has discovered that Neisseria – a genus of bacteria that lives in the human body – is not as harmless as previously thought. In fact, it can cause infections in patients with bronchiectasis, asthma, and chronic obstructive pulmonary disease (COPD).
In a landmark study, published on September 14, 2022, in Cell host and microbe, the team showed conclusive evidence that Neisseria they can cause lung disease and are linked to worsening of bronchiectasis (a type of lung disease) in patients. The scientists were led by Nanyang Technological University, Singapore (NTU Singapore).
Bronchiectasis is a long-term condition in which the airways in the lungs become abnormally enlarged for unknown reasons in up to 50 percent of patients in Singapore. The disease is up to four times more common among Asians compared to their Western counterparts and can also occur after recovery from tuberculosis. In Singapore, research at Tan Tock Seng Hospital described 420 incident hospitalized bronchiectasis patients in 2017. The incidence rate is 10.6 per 100,000 and increases strongly with age.
Despite its prevalence among the elderly, in most cases of bronchiectasis no obvious cause is found and the condition tends to arise spontaneously and without warning.
To unravel the puzzle of why bronchiectasis worsens at a significantly higher rate among older Asian patients, the international team, made up of researchers and hospitals in Singapore, Malaysia, China, Australia and the UK (watch exhibit) — led by LKCMedicine Associate Professor Sanjay Chotirmall, Provost Chair in Molecular Medicine, compared disease and infection data from 225 bronchiectasis patients of Asian origin (Singapore and Malaysia) with those from bronchiectasis patients in Europe.
Neisseria: Not So Harmless After All
Weather Neisseria The species are known to cause meningitis and gonorrhea, but are not known to infect the lungs. Through detailed identification and meticulous characterization, the research team discovered that Neisseria dominated the microbiome of Asian patients with worsening bronchiectasis.
Specifically, patients with bronchiectasis with predominant amounts of a subgroup of Neisseria I call Neisseria subflava (N.subflava), experienced more severe disease and repeated infections (exacerbations) compared with patients with bronchiectasis without as high amounts of Neisseria.
After further investigation using experimental cell and animal models, the research team confirmed that N.subflava causes cell disruption, resulting in inflammation and immune dysfunction in patients with bronchiectasis with this bacterium.
Prior to this discovery, Neisseria was not considered to be a cause of pulmonary infection or severe disease in patients with bronchiectasis.
Lead researcher Professor Chotirmall from LKCMedicine said: “Our findings established, for the first time, that poorer clinical outcomes, such as greater disease severity, poorer lung function and high rates of repeat infection among patients with bronchiectasis, are closely associated with Neisseria bacteria and that this finding is especially important for Asian patients.”
“This discovery is significant because it may change the way we treat our bronchiectasis patients with this bacteria. Doctors will now need to think about Neisseria as a possible “culprit” in patients who are getting worse despite treatment, and run tests to identify those who may harbor this type of bacteria in their lungs. We hope that early identification will lead to personalized therapy and consequently better disease outcomes for Asian patients with this devastating disease,” said Professor Chotirmall, who is also Vice Dean (Faculty Affairs) at LKC Medicine.
This study reflects NTU’s efforts under NTU2025, the University’s five-year strategic plan that addresses humanity’s grand challenges, such as human health. Conducted by international researchers from various disciplines, the study also highlights NTU’s strength and focus on interdisciplinary research.
Wider relevance of Neisseria
In addition to linking Neisseria and severe bronchiectasis, the NTU-led research team also detected the presence of the same bacterium in other more common chronic respiratory conditions, such as severe asthma and chronic obstructive pulmonary disease (COPD), a condition which causes blockage of airflow and breathing. related problems.
Using next-generation sequencing technologies, the team also sought to investigate where this bacteria may have come from, taking samples from the homes of bronchiectasis patients with high amounts of Neisseria in your lungs. The researchers found the presence of the bacterium in the domestic environment, suggesting that indoor space and potentially the tropical climate may favor the presence of this bacterium in the Asian environment.
What is Neisseria?
the Neisseria The bacteria species have been commonly identified as the cause of sexually transmitted infections such as gonorrhea, but also critical meningitis, an inflammation of the fluid and membranes that surround the brain and spinal cord. his subspecies N.subflavaHowever, it is known to be found in the oral mucosa, throat, and upper respiratory tract of humans with no known link to lung infections.
This family of bacteria has always been considered harmless to humans and infections caused by them have not been described until now.
Co-author Professor Wang De Yun from the Department of Ear, Nose and Throat, Yong Loo Lin School of Medicine, National University of Singapore, said: “It is encouraging to see that we have made progress in identifying the Neisseria species of bacteria as the cause of bronchiectasis. worsening, the unlikely culprit that was not originally considered a threat.This comes as a strong reminder that we must not be too complacent when it comes to investigation and exercise greater proactivity in exploring various possibilities, as each seemingly innocent element could be a source of threat to our bodies and health in general.”
Co-author Andrew Tan, Associate Professor of Metabolic Disorders at LKCMedicine, said: “The back translation approach taken in this work was crucial to our success. Starting from the ‘bedside’ where we study real-life patient experiences, we then work backwards to discover the biological process of the bacteria. Thanks to the interdisciplinary nature of the study, the team was able to interact with members from different research disciplines, offering an enjoyable experience while gaining unique insights into the disease.”
Researchers are now looking to conduct further studies and clinical trials of Neisseria eradication of the microbiome through the newly opened LKCMedicine Center for Microbiome Medicine, which seeks to assess the benefits of targeting and treating Neisseria with antibiotics at first detection, in the hope that this will lead to better clinical outcomes for patients with chronic respiratory diseases.
Reference: “Neisseria species as pathobionts in bronchiectasis” by Liang Li, Micheál Mac Aogáin, Tengfei Xu, Tavleen Kaur Jaggi, Louisa LY Chan, Jing Qu, Lan Wei, Shumin Liao, Hong Sheng Cheng, Holly R. Keir, Alison J. Dicker, Kai Sen Tan, Wang De Yun, Mariko Siyue Koh, Thun How Ong, Albert Yick Hou Lim, John A. Abisheganaden, Teck Boon Low, Tidi Maharani Hassan, Xiang Long, Peter AB Wark, Brian Oliver, Daniela I. Drautz-Moses, Stephan C. Schuster, Nguan Soon Tan, Mingliang Fang, James D. Chalmers, and Sanjay H. Chotirmall, September 14, 2022, Cell host and microbe.
- “Trends in Bronchiectasis Among Medicare Beneficiaries in the United States, 2000 to 2007” by Amy E. Seitz, MPH; Kenneth N. Olivier, MD, MPH; Jennifer Adjemian, PhD; Steven M. Holland, MD and D. Rebecca Prevots, PhD, MPH, August 1, 2012, chest diary.
- “Epidemiology and Economic Burden of Bronchiectasis Requiring Hospitalization in Singapore” by Hwee Pin Phua, Wei-Yen Lim, Ganga Ganesan, Joanne Yoong, Kelvin Bryan Tan, John Arputhan Abisheganaden, and Albert Yick Hou Lim, August 12, 2021, ERJ open investigation.
- “Geographic variation in the etiology, epidemiology, and microbiology of bronchiectasis” by Ravishankar Chandrasekaran, Micheál Mac Aogáin, James D. Chalmers, Stuart J. Elborn, and Sanjay H. Chotirmall, May 22, 2018, BMC Pulmonary Medicine.
List of collaborating institutions
- Department of Pharmacology, College of Medicine, Southern University of Science and Technology, Shenzhen, China
- Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
- Biochemical Genetics Laboratory, Department of Biochemistry, St. James’s Hospital, Dublin, Ireland
- Clinical Biochemistry Unit, School of Medicine, Trinity College Dublin, Dublin, Ireland
- School of Civil and Environmental Engineering, Nanyang Technological University, Singapore
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
- University of Dundee, Ninewells Hospital, Medical School, Dundee, Scotland
- Department of Ear, Nose and Throat, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore
- Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore
- Department of Respiratory Medicine and Intensive Care, Tan Tock Seng Hospital, Singapore
- Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore
- Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
- Department of Respiratory Medicine and Critical Care, Peking University Shenzhen Hospital, Shenzhen, China
- Priority Research Center for Healthy Lungs, Hunter Medical Research Institute, School of Medicine and Public Health, University of Newcastle, NSW, Australia
- Department of Sleep and Respiratory Medicine, John Hunter Hospital, New Lambton Heights, NSW, Australia
- Woolcock Institute for Medical Research, University of Sydney, Australia
- School of Life Sciences, Sydney University of Technology, Australia
- Singapore Center for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore
- Faculty of Biological Sciences, Nanyang Technological University, Singapore
- Department of Environmental Sciences and Engineering, Fudan University, Shanghai, China
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