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New study reveals: Infection with 𝘈𝘴𝘱𝘦𝘳𝘨𝘪𝘭𝘭𝘶𝘴 𝘧𝘶𝘮𝘪𝘨𝘢𝘵𝘶𝘴 not only changes the lungs - the intestines and metabolism also play a surprising role.
𝗔𝗻 𝗶𝗻𝘃𝗶𝘀𝗶𝗯𝗹𝗲 𝗶𝗻𝘁𝗿𝘂𝗱𝗲𝗿 𝗽𝘂𝘁𝘀 𝘁𝗵𝗲 𝗱𝗲𝗹𝗶𝗰𝗮𝘁𝗲 𝗯𝗮𝗹𝗮𝗻𝗰𝗲 𝗶𝗻 𝗼𝘂𝗿 𝗹𝘂𝗻𝗴𝘀 𝘁𝗼 𝘁𝗵𝗲 𝘁𝗲𝘀𝘁: 𝘁𝗵𝗲 𝗺𝗼𝗹𝗱 𝘼𝙨𝙥𝙚𝙧𝙜𝙞𝙡𝙡𝙪𝙨 𝙛𝙪𝙢𝙞𝙜𝙖𝙩𝙪𝙨, 𝗵𝗮𝗿𝗺𝗹𝗲𝘀𝘀 𝗶𝗻 𝗻𝗮𝘁𝘂𝗿𝗲, 𝗰𝗮𝗻 𝗯𝗲𝗰𝗼𝗺𝗲 𝗮 𝘀𝗲𝗿𝗶𝗼𝘂𝘀 𝗱𝗮𝗻𝗴𝗲𝗿 𝗶𝗳 𝘁𝗵𝗲 𝗶𝗺𝗺𝘂𝗻𝗲 𝘀𝘆𝘀𝘁𝗲𝗺 𝗶𝘀 𝘄𝗲𝗮𝗸𝗲𝗻𝗲𝗱 - 𝗮𝗻𝗱 𝗰𝗵𝗮𝗻𝗴𝗲 𝘁𝗵𝗲 𝗲𝗻𝘁𝗶𝗿𝗲 𝗯𝗮𝗰𝘁𝗲𝗿𝗶𝗮𝗹 𝘄𝗼𝗿𝗹𝗱 𝗶𝗻 𝘁𝗵𝗲 𝗹𝘂𝗻𝗴𝘀. 𝗕𝘂𝘁 𝘁𝗵𝗮𝘁'𝘀 𝗻𝗼𝘁 𝗮𝗹𝗹: 𝘁𝗵𝗲 𝗶𝗻𝘁𝗲𝘀𝘁𝗶𝗻𝗲𝘀 𝗮𝗻𝗱 𝗺𝗲𝘁𝗮𝗯𝗼𝗹𝗶𝘀𝗺 𝗮𝗹𝘀𝗼 𝗮𝗽𝗽𝗲𝗮𝗿 𝘁𝗼 𝗯𝗲 𝗮𝗳𝗳𝗲𝗰𝘁𝗲𝗱 𝗯𝘆 𝗮 𝗹𝘂𝗻𝗴 𝗶𝗻𝗳𝗲𝗰𝘁𝗶𝗼𝗻.
𝗔 𝗳𝘂𝗻𝗴𝘂𝘀 𝘁𝗵𝗮𝘁 𝗱𝗼𝗲𝘀 𝗺𝗼𝗿𝗲 𝘁𝗵𝗮𝗻 𝗲𝘅𝗽𝗲𝗰𝘁𝗲𝗱
𝘈𝘴𝘱𝘦𝘳𝘨𝘪𝘭𝘭𝘶𝘴 𝘧𝘶𝘮𝘪𝘨𝘢𝘵𝘶𝘴 can be found almost everywhere - in soil, compost or in the air. It is usually harmless for healthy people. However, in patients with a weakened immune system, it can cause severe lung infection, known as invasive aspergillosis. The fungus may potentially alter the oxygen levels in the lungs to a degree that it creates a more suitable environment for certain bacteria – such as 𝘓𝘪𝘨𝘪𝘭𝘢𝘤𝘵𝘰𝘣𝘢𝘤𝘪𝘭𝘭𝘶𝘴 𝘮𝘶𝘳𝘪𝘯𝘶𝘴, typically found in the intestines, oral cavity and lungs of mice - to better survive and potentially thrive. This interaction could possibly influence disease progression and enable new treatment strategies.
𝗙𝗿𝗼𝗺 𝘁𝗵𝗲 𝗹𝘂𝗻𝗴𝘀 𝘁𝗼 𝘁𝗵𝗲 𝗴𝘂𝘁 - 𝗲𝘃𝗲𝗿𝘆𝘁𝗵𝗶𝗻𝗴 𝗶𝘀 𝗰𝗼𝗻𝗻𝗲𝗰𝘁𝗲𝗱
It has long been known that the gut and lungs are closely connected. New data from a research team in Jena has now deepened this understanding. The researchers found evidence that not only the lung microbiome, but also the gut microbiome and certain metabolic products in the blood change during infection of the lungs with 𝘈𝘴𝘱𝘦𝘳𝘨𝘪𝘭𝘭𝘶𝘴 𝘧𝘶𝘮𝘪𝘨𝘢𝘵𝘶𝘴. This so-called “gut-lung axis” could play an important role in future therapy. The work was carried out by scientists from the Cluster of Excellence Balance of the Microverse, the Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (Leibniz-HKI) and the Friedrich-Schiller-University Jena and was recently published in the journal 𝘊𝘦𝘭𝘭 𝘙𝘦𝘱𝘰𝘳𝘵𝘴.
𝗠𝗲𝘁𝗵𝗼𝗱𝗼𝗹𝗼𝗴𝘆 𝗮𝗻𝗱 𝗸𝗲𝘆 𝗳𝗶𝗻𝗱𝗶𝗻𝗴𝘀
The research team used a mouse model for invasive aspergillosis. To find out how the infection affects the microbes in the lungs and intestines, the researchers examined the genetic markers of the microorganisms. To simulate the clinical conditions as realistically as possible, the effects of immunosuppression and antifungal treatment with voriconazole were also considered. The team used specialized methods, including DNA sequencing to identify bacteria in the lungs and intestines, and quantitative PCR to measure the amount of the fungal pathogen 𝘈𝘴𝘱𝘦𝘳𝘨𝘪𝘭𝘭𝘶𝘴 𝘧𝘶𝘮𝘪𝘨𝘢𝘵𝘶𝘴 and the dominant bacterium 𝘓𝘪𝘨𝘪𝘭𝘢𝘤𝘵𝘰𝘣𝘢𝘤𝘪𝘭𝘭𝘶𝘴 𝘮𝘶𝘳𝘪𝘯𝘶𝘴 in the lungs. In addition, metabolomic analyses of plasma and lung tissue were carried out. These analyses record and quantify all metabolic products in a biological system in order to understand changes in the metabolism. In addition, the researchers isolated live bacteria from the lower airways of the mice and co-cultured them with 𝘈𝘴𝘱𝘦𝘳𝘨𝘪𝘭𝘭𝘶𝘴 𝘧𝘶𝘮𝘪𝘨𝘢𝘵𝘶𝘴 to investigate possible interactions. A key finding of the study was, that the fungal infection unbalances both the lung and gut microbiome. In the lungs, this leads to an accumulation of anaerobic bacteria. Particularly striking was the increased growth of 𝘓𝘪𝘨𝘪𝘭𝘢𝘤𝘵𝘰𝘣𝘢𝘤𝘪𝘭𝘭𝘶𝘴 𝘮𝘶𝘳𝘪𝘯𝘶𝘴, suggesting that the fungus creates a microaerophilic niche (low oxygen concentrations) that favors this bacterium.
𝗟𝗶𝗺𝗶𝘁𝗮𝘁𝗶𝗼𝗻𝘀 𝗼𝗳 𝘁𝗵𝗲 𝘀𝘁𝘂𝗱𝘆 - 𝘄𝗵𝗮𝘁 𝗶𝘀 𝗻𝗼𝘁 (𝘆𝗲𝘁) 𝗮𝗻𝘀𝘄𝗲𝗿𝗲𝗱
Analyzing the lung microbiome is challenging because the amount of bacterial DNA in the lung is very low and overlaid by human DNA. “Although we analyzed numerous control samples, the results might still include some misclassifications when it comes to bacteria present at extremely low abundances,” says Liubov Nikitashina, first author of the study. The low DNA yield also mostly limited bacterial identification to the genus level. Improved methods for bacterial DNA extraction from such poorly colonized body sites could make future studies even more meaningful.
The study raises important questions for future research: What role do anaerobic bacteria such as 𝘓𝘪𝘨𝘪𝘭𝘢𝘤𝘵𝘰𝘣𝘢𝘤𝘪𝘭𝘭𝘶𝘴 𝘮𝘶𝘳𝘪𝘯𝘶𝘴 play in modulating 𝘈𝘴𝘱𝘦𝘳𝘨𝘪𝘭𝘭𝘶𝘴 𝘧𝘶𝘮𝘪𝘨𝘢𝘵𝘶𝘴 infections? Could the accumulation of these bacteria in the lungs serve as a diagnostic marker or even enable new therapeutic approaches?
𝗔 𝘀𝗺𝗮𝗹𝗹 𝗳𝘂𝗻𝗴𝘂𝘀 𝘄𝗶𝘁𝗵 𝗮 𝗯𝗶𝗴 𝗲𝗳𝗳𝗲𝗰𝘁
Fungal infections are a serious problem, especially for immunocompromised people or those who are already seriously ill - for example in intensive care units or with cancer. The new findings provide important information on how such infections can be better understood and possibly prevented. In future, it may be possible to specifically influence the microbiome in order to support the body in its fight against the fungus - or to develop new drugs that target precisely this area.
The work on this project was funded by the German Research Foundation, the Federal Ministry of Education and Research and the European Union.
Prof. Dr. Axel A. Brakhage
Molecular and Applied Microbiology
Head of Department
+49 3641 532-1001
axel.brakhage@leibniz-hki.de
Nikitashina L, Chen X, Radosa L, Li K, Straßburger M, Seelbinder B, Böhnke W, Vielreicher S, Nietzsche S, Heinekamp T, Jacobsen ID, Panagiotou G, Brakhage AA (2025) The murine lung microbiome is disbalanced by the human-pathogenic fungus Aspergillus fumigatus resulting in enrichment of anaerobic bacteria, Cell Reports 44
DOI: https://doi.org/10.1016/j.celrep.2025.115442
The growth of 𝘓𝘪𝘨𝘪𝘭𝘢𝘤𝘵𝘰𝘣𝘢𝘤𝘪𝘭𝘭𝘶𝘴 𝘮𝘶𝘳𝘪𝘯𝘶𝘴 (orange), a member of the murine lung microbiome, along the ...
Credits: Liubov Nikitashina (Leibniz-HKI) and Sandor Nietzsche (EMZ-UKJ)
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The growth of 𝘓𝘪𝘨𝘪𝘭𝘢𝘤𝘵𝘰𝘣𝘢𝘤𝘪𝘭𝘭𝘶𝘴 𝘮𝘶𝘳𝘪𝘯𝘶𝘴 (orange), a member of the murine lung microbiome, along the ...
Credits: Liubov Nikitashina (Leibniz-HKI) and Sandor Nietzsche (EMZ-UKJ)
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