Neisseria, a genus of bacteria found in the human body, is not as harmless as previously believed and can cause infections in people who have bronchiectasis, asthma, and chronic obstructive pulmonary disease (COPD). An international team of researchers led by Nanyang Technological University, Singapore (NTU Singapore) made this discovery.
The scientists provided definitive proof that Neisseria species can infect the lungs and are connected to patients’ increasing bronchiectasis (a form of lung disease) in a major study that was published today in Cell Host & Microbe.
Up to 50% of Singaporean patients with bronchiectasis experience abnormal enlargement of their pulmonary airways for unclear reasons. Comparing Asians to their Western counterparts, the condition can be up to four times more common, and it can even develop after a tuberculosis diagnosis.
In Singapore, research at Tan Tock Seng Hospital described 420 incident hospitalised bronchiectasis patients in 2017. The incidence rate is 10.6 per 100,000 and increases strongly with age.
While being more common in elderly people, bronchiectasis typically has no apparent reason and often develops suddenly and without any prior warning.
To unravel the puzzle of why bronchiectasis worsens at a significantly greater rate among older Asian patients, the international team spanning researchers and hospitals in Singapore, Malaysia, China, Australia, and the UK led by LKCMedicine Associate Professor Sanjay Chotirmall, Provost’s Chair in Molecular Medicine, matched disease and infection data from 225 patients with bronchiectasis of Asian (Singapore and Malaysia) origin to those from bronchiectasis patients in Europe.
Neisseria: not so harmless after all
Although Neisseria species are well recognized to cause gonorrhea and meningitis, it is unknown if they can also infect the lungs. The research team discovered that Neisseria predominated the microbiome of Asian patients with deteriorating bronchiectasis through careful identification and characterization.
It is encouraging to see that we have made headway in identifying the Neisseria bacteria species as the cause of worsening bronchiectasis, the unlikely culprit that was originally not considered to be a threat. This comes as a strong reminder that we should not be too complacent when it comes to doing research and exercise more proactiveness in exploring various possibilities, as every seemingly innocent element could be a source of threat to our bodies and overall health.
Professor Wang De Yun
Specifically, bronchiectasis patients with predominant amounts of a subgroup of Neisseria called Neisseria subflava (N. subflava), experienced more severe disease and repeated infections (exacerbations) when compared to patients with bronchiectasis without such high amounts of Neisseria.
Upon 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 bronchiectasis patients with this bacterium.
Prior to this discovery, Neisseria was not considered to be a cause of lung infection or severe disease in bronchiectasis patients.
Lead investigator Prof Chotirmall from LKCMedicine, said, “Our findings have established, for the first time, that poorer clinical outcomes such as greater disease severity, poorer lung function and high repeated infection rates among bronchiectasis patients are closely associated to the bacteria Neisseria and that this finding is especially important for Asian patients.”
“This discovery is significant because it can change how we treat our bronchiectasis patients with this bacterium. Doctors will now need to think about Neisseria as a potential ‘culprit’ in patients who are worsening despite treatment, and to conduct tests to identify those who may be harbouring this type of bacteria in their lungs. We hope that early identification will lead to personalised therapy, and consequently, better disease outcomes for Asian patients with this devastating disease,” said Prof Chotirmall, who is also Assistant Dean (Faculty Affairs) at LKCMedicine.
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 across various disciplines, the study also highlights NTU’s strength and focus on interdisciplinary research.
Broader relevance of Neisseria
The NTU-led research team discovered a connection between Neisseria and severe bronchiectasis as well as the presence of the same bacteria in other more prevalent chronic respiratory conditions like severe asthma and Chronic Obstructive Pulmonary Disease (COPD), a condition that impairs breathing and causes airflow blockage.
The scientists also collected samples from the residences of bronchiectasis patients with high levels of Neisseria in their lungs in an effort to learn more about the origins of this bacterium.
The discovery of the bacteria by the researchers in the home environment raises the possibility that the tropical climate and indoor living conditions in Asia may favor the presence of this bacteria.
What is Neisseria?
Both critically life-threatening meningitis, an inflammation of the fluid and membranes surrounding the brain and spinal cord, and sexually transmitted infections like gonorrhea, such as gonorrhoea, have been linked to the Neisseria bacteria species. Its sub-species N. subflava, however, is known to be found in the oral mucosa, throat, and upper airway of humans previously without any known link to lung infections.
This family of bacteria has always been thought of as harmless to humans, and infections caused by them have not been described until now.
Co-author, Professor Wang De Yun from the Department of Otolaryngology at the Yong Loo Lin School of Medicine, National University of Singapore, said, “It is encouraging to see that we have made headway in identifying the Neisseria bacteria species as the cause of worsening bronchiectasis, the unlikely culprit that was originally not considered to be a threat. This comes as a strong reminder that we should not be too complacent when it comes to doing research and exercise more proactiveness in exploring various possibilities, as every seemingly innocent element could be a source of threat to our bodies and overall health.”
Co-author Andrew Tan, Associate Professor of Metabolic Disorders from LKCMedicine, said, “The reverse translational approach adopted in this work was crucial to our success. Starting from the ‘bedside’ where we studied real-life patient experiences, we then worked backwards to uncover 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.”
Through the recently established LKCMedicine Centre for Microbiome Medicine, the researchers are now seeking to carry out additional research and clinical trials aimed at eliminating Neisseria from the microbiome. They want to assess the advantages of focusing on and treating Neisseria with antibiotics at the first sign of infection in the hopes of improving clinical outcomes for patients with long-term respiratory conditions.
