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With increasing age, the metabolic activity of intestinal bacteria changes - to the detriment of the host, as a research team from Kiel and Jena discovered.
-Metabolic activity of the microbiome is significantly reduced in old age, as the analysis of animal data and computer models shows
-Bacteria produce fewer vital substances that the body needs. This can contribute to ageing
-The repeated and lifelong transfer of a “young” microbiome halts ageing processes in mice, according to another study from Kiel
The intestine is home to a complex ecosystem of microorganisms. This so-called gut microbiome plays an important role in health, disease and ageing. Various studies suggest that the microbiome “ages” and drives the host's ageing processes. It was previously unclear which mechanisms the microbiome uses to control ageing in the host. This question was investigated by a research team led by Professor Christoph Kaleta, Faculty of Medicine at Kiel University (CAU) and Cluster of Excellence “Precision Medicine in Chronic Inflammation” (PMI), and Dr. Christiane Frahm from Jena University Hospital (UKJ). While Kiel contributed its expertise in metabolic modeling, Jena provided central experimental data for the analyses. This work was carried out as part of the Marie Sklodowska-Curie Innovative Training Network SmartAge (ITN) coordinated by Jena under Horizon 2020.
In the study, the researchers were able to show that there is a strong reduction in the metabolic activity of the microbiome during ageing. “These changes are directly reflected in the metabolic processes of the host,” emphasizes Kaleta, who heads the Medical Systems Biology working group and is also involved in the Collaborative Research Centre (CRC 1182) ‘Origin and Function of Metaorganisms’. The results were recently published in the journal Nature Microbiology. A central goal of further research is to find ways to reverse these age-related changes in the microbiome, for example through special food supplements. In another study published in the journal Microbiome, the Cluster of Excellence PMI succeeded in slowing down ageing processes in an animal model by means of a repeated microbial rejuvenation treatment.
Computer models serve as an image for the metabolism of intestinal bacteria
It has long been known that the microbiome changes with age and is involved in age-related processes. “Studies show that the transfer of the microbiome of older animals to younger animals can increase inflammatory processes, while conversely the transplantation of a young microbiome in older animals showed rejuvenating effects - a phenomenon that has been observed in various species,” says Frahm, who heads the Gut-Brain Interaction and Ageing research group at the UKJ.
“To better understand this, we created computer models of the metabolism of the host and microbiome,” explains Kaleta. Molecular biological data from intestinal, brain, liver tissue and stool samples from mice of different age groups were used for this. Using the data from the tissue and stool analyses, a separate computer model was created for each mouse that represents the organs of the host and the microbiome. This makes it possible to investigate which molecules are exchanged between the host and the microbiome. “We have discovered, for example, that the host often uses the microbiome as a kind of recycler,” Kaleta continues. The host provides the microbiome with metabolic end products, which in turn are used to produce substances that are essential for the host. This enables a more efficient use of resources, although this decreases with age.
Age-related decline in microbial metabolic activity
A key finding of the study was that the metabolic activity of the microbiome decreases significantly with increasing age. “The individual bacterial species no longer work together as efficiently and increasingly compete for nutrients,” explains first author Lena Best. This has a direct impact on the host, as many essential cell functions - including the stabilization of the intestinal barrier as well as repair and remodelling processes - depend on the microbiome.
Stool transfer: microbiome of young mice slows down ageing
Another study by the Cluster of Excellence led by Professor Philip Rosenstiel on mice has shown that it is indeed possible to reduce ageing processes in the host and also in the microbiome. “There are already isolated indications of this from earlier studies, but for the first time we have attempted to rejuvenate the microbiome over the entire lifespan of a mouse,” explained Rosenstiel, member of the board of the Cluster of Excellence PMI and Director of the Institute of Clinical Molecular Biology (IKMB) at the Faculty of Medicine of Kiel University and the University Medical Center Schleswig-Holstein (UKSH), Kiel Campus. For this purpose, the animals were transferred stool from young mice every eight weeks for two years, while the animals in the control group received the microbiome from mice of the same age via stool transfer. “We were actually able to reduce some signs of aging,” emphasizes first author PD Dr. Felix Sommer, head of the Functional Host Microbiome Research group at the IKMB. “Movement coordination improved and the intestinal barrier was preserved.” Further analyses also revealed that fewer pro-inflammatory factors were found in the young microbiome. In the host, i.e. the mouse, typical signs of inflamm-aging decreased. Inflamm-aging, a mild, persistent inflammation in the tissue, is considered a biological feature of the ageing process and plays a role in various diseases.
New perspectives for microbiome-based therapies
The results of the study show that the microbiome plays a key role in age-related changes in the host. They also open up new approaches for therapeutic interventions. “We are now investigating how we can specifically reverse the age-related changes in the microbiome,” explains Kaleta. Initial studies with certain food supplements using simple model organisms show that it may indeed be possible to specifically influence the microbiome. This represents an important step towards the development of microbiome-based therapies against ageing.
Pictures can be downloaded:
https://www.precisionmedicine.de/fileadmin/user_upload/cluster/pmi/pressebilder/...
Visualization of bacteria of the microbiome
© fotogurmespb – stock.adobe.com
https://www.precisionmedicine.de/fileadmin/user_upload/cluster/pmi/portraitbilde...
Professor Christoph Kaleta, member of the Cluster of Excellence “Precision Medicine in Chronic Inflammation” (PMI), the Collaborative Research Center “Origin and Function of Metaorganisms” and head of the Medical Systems Biology working group at the Institute of Experimental Medicine at CAU and UKSH
© Sascha Klahn
https://www.uni-kiel.de/de/pressemitteilungen/portraitbilder/philip-rosenstiel.j...
Professor Philip Rosenstiel, Director at the Institute of Clinical Molecular Biology, CAU and UKSH, and board member of the Cluster of Excellence “Precision Medicine in Chronic Inflammation” (PMI).
© Tebke Böschen/Uni Kiel
Link:
https://www.precisionmedicine.de/en/the-microbiome-influences-ageing
Prof. Dr. Christoph Kaleta
Faculty of Medicine, CAU
Institute for Experimental Medicine, CAU Kiel, UKSH
Tel.: 0431/500-30340
c.kaleta@iem.uni-kiel.de
Dr. Christiane Frahm
Department of Neurology
Jena University Hospital
Tel.: 03641/9325909
christiane.frahm@med.uni-jena.de
Prof. Dr. Philip Rosenstiel
Faculty of Medicine, CAU
Institute for Clinical Molecular Biology, CAU Kiel, UKSH
Tel.: 0431/500-15105
p.rosenstiel@mucosa.de
Lena Best et al.: Metabolic modeling reveals the aging-associated decline of host-microbiome metabolic interactions in mice. Nat Microbiol. 10, 973–991 (2025). https://doi.org/10.1038/s41564-025-01959-z
Felix Sommer, Joana P. Bernardes et al.: Life-long microbiome rejuvenation improves intestinal 1 barrier function and inflammaging in mice. Microbiome 13, 91 (2025). https://doi.org/10.1186/s40168-025-02089-8
Visualization of bacteria of the microbiome
© fotogurmespb – stock.adobe.com
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Visualization of bacteria of the microbiome
© fotogurmespb – stock.adobe.com
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