Every breath we take isn't ours; it's shared with trillions of tiny microbes that make our lungs home. Surprised? But aren’t lungs supposed to be sterile? For a long time, that is what scientists thought. Now we know better — they’re anything but!

Although the microbiome (community of microbes) of the gut (intestinal tract) steals the limelight in medicine and research, modern studies reveal that the lungs have their own vibrant microbial world. The lung microbiome is composed of bacteria, viruses, and fungi that reside inside the lungs, shaping health and disease in dynamic ways.

Scientists have also found traces of archaea (ancient microbes), mycoplasma (bacteria without a cell wall), and even protozoa (microscopic one-celled animals), making the lung a surprisingly diverse and mysterious ecosystem.¹ These microorganisms are crucial for immune balance and could hold keys to understanding several respiratory diseases.²

Idiopathic pulmonary fibrosis (IPF) is a chronic (long-term) and incurable lung disease that gets worse over time, making each breath harder than the last. In this condition, gas-exchanging regions of the lung become fibrotic (stiff and scarred), leading to progressive shortness of breath, a persistent dry cough, fatigue, and chest discomfort.³

The term “idiopathic” means that its underlying cause remains unknown — a mystery that continues to puzzle scientists and clinicians. Left untreated, the disease is associated with a poor outcome, as many patients progress to respiratory failure within a few years of diagnosis (identifying the medical condition), often resulting in death.

Diagnosis is particularly challenging and typically requires the systematic exclusion of other known causes of pulmonary fibrosis, such as connective tissue diseases, environmental exposures, or drug toxicity.^4,5

What Shapes the Lung Microbiome?

The microbes living in our lungs are not random; several factors determine which species can thrive there. Our genetic makeup influences, at least in part, which microbes are more likely to reside in our lungs.⁶

In addition, small amounts of material from the mouth and upper airways, known as microaspirations, continually introduce new microbes, helping to influence and sustain the lung’s microbial community in both health and disease.⁷

Even more fascinating is the connection between the lungs and gut, known as the gut-lung axis. Microbes in the intestinal tract can influence the lung microbiome, helping explain why gut conditions such as inflammatory bowel disease sometimes overlap with chronic respiratory diseases.

What about probiotics (beneficial live gut flora) and prebiotics (food for beneficial gut flora), the widely promoted “gut helpers”? While these supplements can reshape gut microbiomes, their impact on the lung microbiome appears to be much more limited.^8,9,10

Our lungs might seem simple, but they host a bustling microbial world. These tiny residents may hold clues to why some people’s lungs stay healthy while others struggle — a hidden universe influencing every breath we take.

Unmasking the Role of Lung Microbiome in Idiopathic Pulmonary Fibrosis

Changes in the lung microbiome are increasingly believed to influence the onset and progression of IPF.¹¹ Studying these subtle shifts in the microbial community of our lungs could offer new ways to improve the diagnosis and treatment of the disease.

A diverse microbiome appears to protect our lungs, but studies have found that IPF patients have lower diversity of lung microbiota compared to healthy individuals. At the same time, the total bacterial load is higher in the lungs of IPF patients. This higher bacterial burden is linked to worse outcomes, including faster disease progression, rapid scarring, and higher mortality (death).^{11, 12}

Interestingly, the bacterial composition in the lungs is altered in IPF, with certain types, such as Streptococcus and Staphylococcus, becoming more abundant. Some of these microbes may take advantage of the already damaged lung environment to promote fibrosis.

When the microbial imbalance is disturbed, it can overstimulate the immune system to drive inflammation (a defence response to injury or infection causing swelling and irritation in tissues) and contribute to lung fibrosis.^{12, 13}

Emerging research also suggests viruses and fungi influence lung health. The latent (hidden or dormant) viruses, such as Epstein-Barr virus and human herpesvirus, have been detected in the lung tissue of IPF patients. Although these viruses often remain dormant, they can reactivate under certain conditions, fuelling inflammation and triggering pathways that promote the scarring of lungs.

Fungal species may also shape the immune environment in the lungs, though their role is still being explored.¹³

While we don’t yet fully understand the role of the lung microbiome in IPF, evidence suggests it could be both a trigger and a consequence. Changes in microbial communities may contribute to inflammation and scarring, pushing the disease forward.

At the same time, the progressing fibrosis and lung damage can alter the lung environment, encouraging further shifts in microbial populations. In other words, the lung microbiome and IPF may be caught in a vicious cycle, each influencing the other.^{11, 14, 15}

The Diagnostic and Therapeutic Potential of the Lung Microbiome

Understanding microbial interactions in the lung may one day help develop strategies to slow or prevent scarring, making the lung microbiome a promising target for diagnosis and developing new therapies in the management of IPF.¹⁵

Antibiotics like cotrimoxazole (that target specific bacteria) have shown some benefits, including improved quality of life and reduced mortality in IPF patients. Researchers are also exploring microbiome-directed therapies, including probiotics, to help regulate the immune system, though human studies are still limited.

Managing related conditions, such as acid reflux — when stomach acid flows back up to the food pipe, causing heartburn — may further support a healthy lung microbial balance.^14-18

Did you know that the microbes living in our lungs might one day help doctors detect IPF earlier? Research suggests that changes in the lung microbiome could serve as a kind of biological “early warning system".⁷

Looking even further ahead, scientists are imagining treatments that go beyond traditional drugs — like microbiome transplants or engineered microbes designed to influence the immune pathways involved in lung stiffening and scarring.^{7, 19}

While these ideas are still mostly in the laboratory and haven’t been tested in humans yet, understanding how the lung microbiome works could one day improve quality of life — not just for people with IPF, but also for those at risk and anyone interested in keeping their lungs healthy.

 Bibliography

1. Chen J, Li T, Ye C, Zhong J, Huang JD, Ke Y, Sun H. The lung microbiome: a new frontier for lung and brain disease. Int J Mol Sci. 2023;24(3):2170. doi:10.3390/ijms24032170.
2. Li R, Li J, Zhou X. Lung microbiome: new insights into the pathogenesis of respiratory diseases. Signal Transduct Target Ther. 2024;9(1):19. doi:10.1038/s41392-023-01722-y.
3. Muri J, Durcová B, Slivka R, Vrbenská A, Makovická M, Makovický P, et al. Idiopathic Pulmonary Fibrosis: Review of Current Knowledge. Physiol Res. 2024;73(4):487-97. doi:10.33549/physiolres.935322.
4. Spagnolo P, Tonelli R, Cocconcelli E, Stefani A, Richeldi L. Idiopathic pulmonary fibrosis: diagnostic pitfalls and therapeutic challenges. Multidiscip Respir Med. 2012;7(1):42. doi:10.1186/2049-6958-7-42.
5. Prasad R, Gupta N, Singh A, Gupta P. Diagnosis of idiopathic pulmonary fibrosis: Current issues. Intractable Rare Dis Res. 2015;4(2):65–9.
6. Molyneaux PL, Willis-Owen SAG, Cox MJ, James P, Cowman S, Loebinger M, et al. Host-Microbial Interactions in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2017;195(12):1640-50. doi:10.1164/rccm.201607-1408OC.
7. Lipinski JH, Moore BB, O’Dwyer DN. The evolving role of the lung microbiome in pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2020;319(4):L675–82. doi:10.1152/ajplung.00308.2020.
8. Göktürk K, Tülek B, Kanat F, Maçin S, Arslan U, Shahbazova M, et al. Gut microbiota profiles of patients with idiopathic pulmonary fibrosis. Exp Lung Res. 2024;50(1):278–89. doi:10.1080/01902148.2024.2405915.
9. Du B, Fu Y, Han Y, Sun Q, Xu J, Yang Y, et al. The lung-gut crosstalk in respiratory and inflammatory bowel disease. Front Cell Infect Microbiol. 2023;13:1218565. doi:10.3389/fcimb.2023.1218565.
10. Puiu R, Motoc NS, Lucaciu S, Ruta MV, Rajnoveanu RM, Todea DA, et al. The role of lung microbiome in fibrotic interstitial lung disease—A systematic review. Biomolecules. 2024;14(3):247. doi:10.3390/biom14030247.
11. Amati F, Festi G, Pozzi-Mucelli R, Orzes N, Confalonieri P, Confalonieri M. Lung microbiome in idiopathic pulmonary fibrosis and interstitial lung diseases: a review. Int J Mol Sci. 2022;23(2):1029. doi:10.3390/ijms23021029.
12. Tong X, Su F, Xu X, Xu H, Yang T, Xu Q, et al. Alterations to the lung microbiome in idiopathic pulmonary fibrosis patients. Front Cell Infect Microbiol. 2019;9:149. doi:10.3389/fcimb.2019.00149.
13. Shadid A, Rich HE, DeVaughn H, Domozhirov A, Doursout MF, Weng-Mills T, et al. Persistent microbial infections and idiopathic pulmonary fibrosis — an insight into non-typeable Haemophilus influenzae pathogenesis. Front Cell Infect Microbiol. 2024;14:1479801. doi:10.3389/fcimb.2024.1479801.
14. Spagnolo P, Molyneaux PL, Bernardinello N, Cocconcelli E, Biondini D, Fracasso F, Tinè M, Saetta M, Maher TM, Balestro E. The role of the lung’s microbiome in the pathogenesis and progression of idiopathic pulmonary fibrosis. Int J Mol Sci. 2019;20(22):5618. doi:10.3390/ijms20225618.
15. Fastrès A, Felice F, Roels E, Moermans C, Corhay JL, Bureau F, Louis R, Clercx C, Guiot J. The lung microbiome in idiopathic pulmonary fibrosis: a promising approach for targeted therapies. Int J Mol Sci. 2017;18(12):2735. doi:10.3390/ijms18122735.
16. Shulgina L, Cahn AP, Chilvers ER, Parfrey H, Clark AB, Wilson EC, Twentyman OP, Davison AG, Curtin JJ, Crawford MB, Wilson AM. Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: a randomised controlled trial. Thorax. 2013 Feb;68(2):155-162. doi:10.1136/thoraxjnl-2012-202403.
17. Whiteside SA, McGinniss JE, Collman RG. The lung microbiome: progress and promise. J Clin Invest. 2021;131(15):e150473. doi:10.1172/JCI150473.
18. Raghu G, Pellegrini CA, Yow E, Flaherty KR, Meyer K, Noth I, et al. Laparoscopic anti-reflux surgery for the treatment of idiopathic pulmonary fibrosis (WRAP-IPF): a multicentre, randomised, controlled phase 2 trial. Lancet Respir Med. 2018;6(9):707-14. doi:10.1016/S2213-2600(18)30301-1.
19. Hern KE, Prindle A. Towards airway microbiome engineering for improving respiratory health. Adv Drug Deliv Rev. 2025;225:115662. doi:10.1016/j.addr.2025.115662.

Frequently Asked Questions (FAQs)

Q1. Aren’t the lungs supposed to be sterile?

For a long time, scientists believed the lungs were sterile. Modern research now shows that the lungs host their own diverse microbiome — including bacteria, viruses, fungi, and even archaea — which can influence health and disease.

Q2. What exactly is the lung microbiome?

The lung microbiome refers to the community of microorganisms (bacteria, viruses, fungi, and others) that naturally live in the lungs. They interact with the immune system and may help maintain balance in lung health.

Q3. How do microbes get into the lungs?

Small amounts of material from the mouth and upper airways, called microaspirations, continually introduce new microbes into the lungs. Air inhalation and the gut–lung axis also play a role.

Q4. What is idiopathic pulmonary fibrosis (IPF)?

IPF is a chronic, progressive lung disease where lung tissue becomes stiff and scarred, making it harder to breathe. The cause is unknown (“idiopathic”), and the disease often worsens over time.

Q5. How is the lung microbiome linked to IPF?

Research suggests that changes in the lung microbiome — such as higher bacterial burden or reduced diversity — may accelerate scarring in IPF. Certain bacteria, viruses, and fungi may disrupt immune balance and worsen the disease.

Q6. Can probiotics or prebiotics help lung health like they do for the gut?

While probiotics and prebiotics are well studied for gut health, their role in the lung microbiome is less clear. Current evidence suggests their direct impact on the lungs is limited.

Q7. What about acid reflux and lung health?

Managing acid reflux (when stomach acid flows back into the oesophagus or food pipe) may help reduce harmful microaspirations into the lungs, supporting a healthier lung microbial balance.

Q8. Can the lung microbiome be used for early diagnosis of IPF?

Emerging research suggests that specific microbial patterns could serve as biomarkers for early detection of IPF, but this is still being studied.

Q9. Are there new treatments being developed based on the lung microbiome?

Yes — scientists are exploring innovative approaches like microbiome transplants or even engineered microbes that could influence immune pathways involved in fibrosis. These remain experimental and are not yet tested in humans.

Q10. Why does this research matter?

Understanding the lung microbiome could open the door to earlier diagnosis, better treatments, and improved quality of life for people with IPF — and possibly help protect lung health in the general population.

Authors

Siddhi Vinod Mahajan and Dr. Satish Sasikumar*

Genetics and Molecular Biology Research Centre, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Tathawade, Pune, Maharashtra, PIN-411033, India. Author for correspondence: Dr. Satish Sasikumar, Ph.D. (satish.sasikumar@dpu.edu.in). Ms. Siddhi V. Mahajan (sidddhiii.mahajan@gmail.com) is a student of the Third Year Bachelor of Technology in Medical Biotechnology degree programme at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Tathawade, Pune.