Bacteria previously thought harmless can worsen lung disease

A team of international scientists led by the Nanyang Technological University, Singapore (NTU Singapore) has discovered that Neisseria — a genus of bacteria that lives in the human body — is not as harmless as previously thought, and can cause infection in patients with bronchiectasis, asthma and chronic obstructive pulmonary disease (COPD).

The Neisseria bacteria species have been commonly identified as the cause of sexually transmitted infections like gonorrhoea as well as meningitis — an inflammation of the fluid and membranes surrounding the brain and spinal cord. A subspecies, Neisseria subflava (N. subflava), is known to be found in the oral mucosa, throat and upper airway of humans, and has always been thought of as harmless — until now.

Bronchiectasis is a long-term condition where the airways of the lungs become abnormally enlarged for unknown reasons. The disease is up to four times more prevalent among Asians as compared to their Western counterparts and can also occur following recovery from tuberculosis; the incidence rate also increases strongly with age. Yet despite its prevalence among older people, no obvious cause is found in most cases of bronchiectasis and the condition tends to arise spontaneously and without 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 — matched disease and infection data from 225 patients with bronchiectasis of Asian (Singapore and Malaysia) origin to those from bronchiectasis patients in Europe. Their results were published in the journal Cell Host & Microbe.

Through detailed identification and meticulous characterisation, the research team found that Neisseria dominated the microbiome of Asian patients with worsening bronchiectasis. Specifically, bronchiectasis patients with predominant amounts of 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.

“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,” said lead investigator Associate Professor Sanjay Chotirmall from the Lee Kong Chian School of Medicine (LKCMedicine), a partnership between NTU Singapore and Imperial College London.

“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.”

Aside from linking Neisseria and severe bronchiectasis, the research team also detected the presence of the same bacteria in other more common chronic respiratory conditions such as severe asthma and COPD — a condition that causes airflow blockage and breathing-related problems.

Using next-generation sequencing technologies, the team also sought to investigate where this bacterium may come from and sampled the homes of bronchiectasis patients with high amounts of Neisseria in their lungs. The researchers found the presence of the bacteria in the home environment, suggesting that the indoor living space and potentially the tropical climate may favour the presence of this bacteria in the Asian setting.

“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,” said study co-author Professor Wang De Yun, from NTU Singapore. “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.”

The researchers are now looking to conduct further studies and clinical trials of Neisseria eradication from the microbiome through the newly launched LKCMedicine Centre for Microbiome Medicine, which is seeking to evaluate the benefits of targeting and treating Neisseria with antibiotics at first detection, with the hope that this will lead to better clinical outcomes for patients with chronic respiratory conditions.

Image credit: iStock.com/sturti

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