Scientists have discovered that a type of bacteria is not as harmless as previously thought. Bronchiectasis can actually cause infections in patients with asthma and chronic obstructive pulmonary disease (COPD).
An international study led by Singaporean scientists has found that bacteria previously thought to be harmless can worsen existing lung diseases.
An international team of scientists discovered it neisseria — a genus of bacteria living in the human body — is not as harmless as previously thought. In fact, bronchiectasis can cause infections in patients with asthma and chronic obstructive pulmonary disease (COPD).
In a landmark study published on September 14, 2022 Cell Host and Microbe, the team showed the final proof of this neisseria species can cause lung disease and have been associated with worsening bronchiectasis (a type of lung disease) in patients. The scientists were led by Singapore’s Nanyang Technological University (NTU Singapore).
Bronchiectasis is a long-term condition in which the airways of the lungs are abnormally enlarged for unknown reasons in up to 50 percent of Singaporean patients. The disease is four times more common in Asians than in their Western counterparts, and can occur even after recovery from TB.[1] Research at Tan Tock Seng Hospital in Singapore described 420 bronchiectasis hospitalizations in 2017.[2] The incidence rate is 10.6 per 100,000 and increases strongly with age.
Despite its prevalence among the elderly, most bronchiectasis have no apparent cause, and the condition tends to develop spontaneously and without warning.[3]
An international team involving researchers and hospitals in Singapore, Malaysia, China, Australia and the United Kingdom to unravel the puzzle of why bronchiectasis worsens significantly among older Asian patients (to see Additional) — The Provost Chair in Molecular Medicine, led by LKCMedicine Associate Professor Sanjay Chotirmall, matched disease and infection data from 225 bronchiectasis patients in Asia (Singapore and Malaysia) to bronchiectasis patients in Europe.
Neisseria: not so harmless
to work neisseria species are well known to cause meningitis and gonorrhea, they are not known to infect the lungs. Through detailed identification and careful characterization, the research team found that neisseria dominated the microbiome of Asian patients with worsening bronchiectasis.
In particular, a subgroup of patients with bronchiectasis prevails neisseria he called neisseria subflava (N. subflava), experienced more severe disease and reinfections (exacerbations) than patients with bronchiectasis without such a high amount. neisseria.
The research team confirmed this after conducting further studies using experimental cell and animal models N. subflava causes cell disruption, resulting in inflammation and immune dysfunction in patients with bacterial bronchiectasis.
In the picture, Neisseria (N. subflava) is detected in the lung tissue of patients with bronchiectasis. Red shows detection of N. subflava and blue shows respiratory tract cell nuclei. Credit: Cell Host and Microbe
Before this discovery, Neisseria was not considered a cause of lung infection or severe disease in patients with bronchiectasis.
Lead researcher Professor Chotirmall from LKCMedicine said: “Our findings are the first to identify that worse clinical outcomes, such as worse disease severity, poorer lung function and higher reinfection rates among patients with bronchiectasis, are strongly associated with Neisseria and bacteria. This finding is particularly important for Asian patients.
“This discovery is significant because it may change the way we treat our bronchiectasis patients with this bacterium. Doctors now have to consider Neisseria as a potential “culprit” in patients who worsen despite treatment, and run tests to identify those who harbor this type of bacteria in their lungs. We hope that early identification will lead to personalized therapy and ultimately better disease outcomes for Asian patients with this devastating disease,” said Professor Chotirmall, Assistant Dean (Faculty Affairs) at LKCMedicine.
This research reflects NTU’s efforts under NTU2025, the University’s five-year strategic plan to address humanity’s great challenges such as human health. Research conducted by international researchers from a variety of disciplines highlights NTU’s strength and focus on interdisciplinary research.
The wider relevance of Neisseria
In addition to establishing a link between Neisseria and severe bronchiectasis, the NTU-led research team also found the same bacteria to be present in other more common chronic respiratory diseases such as severe asthma and Chronic Obstructive Pulmonary Disease (COPD) – a condition that causes airflow obstruction and difficulty breathing. situation. – related problems.
Using next-generation sequencing technologies, the team sought to investigate where this bacteria might have come from and sampled homes of patients with bronchiectasis who had high levels. neisseria in the lungs. The researchers found the presence of the bacteria in the home environment, suggesting that indoor living space and potentially the tropical climate may have contributed to the presence of these bacteria in the Asian environment.
What is Neisseria?
The neisseria Bacterial species are commonly identified as the cause of sexually transmitted infections such as gonorrhea, but also critical meningitis – inflammation of the fluid and membranes that surround the brain and spinal cord. Its subspecies N. subflavahowever, it is known to be found in the oral mucosa, throat, and upper respiratory tract of people with no prior known association with lung infections.
This family of bacteria has always been considered harmless to humans, and the infections they cause have not been described until now.
Co-author Professor Wang De Yun, from the Department of Otolaryngology at the National University of Singapore’s Yong Loo Lin School of Medicine, said: “It is encouraging to see that we have made progress in identifying Neisseria species as the cause. worsening bronchiectasis, a likely culprit that was not initially considered a threat. It’s a reminder that we shouldn’t be too complacent when it comes to doing research and practicing more proactively exploring different possibilities, because every seemingly innocent element can be a source of danger to our bodies and our overall health.”
Co-author Andrew Tan, Associate Professor of Metabolic Disorders from LKCMedicine, said: “The reverse translational approach taken in this study was critical to our success. Starting at the “bedside” where we studied the real-life experiences of patients, we worked backwards to uncover the biological process of the bacteria. Due to the interdisciplinary nature of the research, the team was able to interact with members from different research disciplines, providing an enjoyable experience while gaining unique insights into the disease.
Researchers are now working on further studies and clinical trials neisseria eradication of the microbiome through the newly launched LKCMedicine Center for Microbiome Medicine, which seeks to evaluate the benefits of targeting and treatment neisseria with antibiotics at first detection in the hope of leading to better clinical outcomes in patients with chronic respiratory diseases.
Reference: “neisseria species as pathobionts in bronchiectasis” 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, Tun Hou Ong, Albert Yik Hou Lim, John A. Abisheganaden, Tek Boon Low, Tidi Maharani Hassan, Xiang Long, Peter AB Wark, Brian Oliver, Daniela I. Drautz-Moses, Stefan C. Schuster, Nguan Soon Tan, Mingliang Fang, James D. Chalmers, and Sanjay H. Chotirmall, 14 September 2022, Cell Host and Microbe.
DOI: 10.1016/j.chom.2022.08.005
Notes
- “Bronchiectasis Trends Among Medicare Beneficiaries in the United States, 2000-2007” 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 magazine.
DOI: 10.1378/chest.11-2209 - “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 Abiseganaden and Albert Yick Hou Lim, 12 August 2021. ERJ Open Research.
DOI: 10.1183/23120541.00334-2021 - Ravishankar Chandrasekaran, Micheál Mac Aogáin, James D. Chalmers, Stuart J. Elborn, and Sanjay H. Chotirmall, “Geographic variation in the etiology, epidemiology, and microbiology of bronchiectasis,” May 22, 2018. BMC Pulmonary Medicine.
DOI: 10.1186/s12890-018-0638-0
Additional
List of collaborating institutions
- Department of Pharmacology, Faculty of Medicine, Southern University of Science and Technology, Shenzhen, China
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
- Laboratory of Biochemical Genetics, Department of Biochemistry, St. James Hospital, Dublin, Ireland
- Department of Clinical Biochemistry, 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, School of Medicine, Dundee, Scotland
- Department of Otolaryngology, Infectious Disease Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore
- Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore
- Department of Respiratory and Critical Care Medicine, 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 Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, NSW, Australia
- Woolcock Institute of Medical Research, University of Sydney, Australia
- School of Life Sciences, University of Technology, Sydney, Australia
- Singapore Center for Environmental Science Engineering (SCELSE), Nanyang Technological University, Singapore
- School of Biological Sciences, Nanyang Technological University, Singapore
- Department of Environmental Science and Engineering, Fudan University, Shanghai, China
