The aging of the gut microbiome involves a shift in the relative numbers of different microbial species. As a result the production of some beneficial metabolites declines while inflammatory microbial activities increase. At present there are few practical ways to permanently adjust the gut microbiome, one of which is the transplantation of fecal matter from a donor. Animal studies have demonstrated that fecal microbiota transplantation from a young animal to an old animal rejuvenates the gut microbiome, improves health, and extends life. Human studies are relatively limited, but this approach to treatment is established for patients with C. difficile infection. It remains to be seen as to whether it will find broader use, versus the more challenging approach of developing the means to culture a full or close to full gut microbiome artificially.
The gut microbiota has become a potential therapeutic target in several diseases, including cardiovascular diseases. Animal models of fecal microbiota transplantation (FMT) were established in elderly and young rats. 16S rRNA sequencing revealed that the gut microbiota of the recipients shifted toward the profile of the donors, with concomitant cardiac structure and diastolic function changes detected via ultrasound and positron emission tomography-computed tomography (PET-CT). The elderly recipient rats that received young fecal bacteria presented an overall reduction in aging characteristics, whereas young rats that received reverse transplantation presented an overall increase in aging characteristics.
After FMT, the structure and function of the hearts of the recipient rats changed correspondingly. The age-related thickening of the left ventricular wall and interventricular septum at the organ level, along with the disordered arrangement of cardiomyocytes and increased interstitial volume at the tissue level, decreased following FMT in young rats. These structural modifications are accompanied by alterations in cardiac function; however, systolic function did not significantly change, whereas diastolic function notably improved. The young rats that received reverse transplantation presented the opposite results as the aged rats did; that is, the structure and function of the heart were lower in the reverse-transplanted rats than in the same-aged control rats.
A group of significantly enriched myocardial metabolites detected by liquid chromatography-mass spectrometry (LC/MS) were involved in the fatty acid β-oxidation process. Together with altered glucose uptake, as revealed by PET-CT, changes in ATP content and mitochondrial structure further verified a metabolic difference related to energy among rats transplanted with the gut microbiota from donors of different ages. This study demonstrated that gut microbes may participate in the physiological aging process of the rat heart by regulating oxidative stress and autophagy. The gut microbiota has been shown to be involved in the natural aging of the heart at multiple levels, from the organ level to the metabolically plastic myocardiocytes and associated molecules.
Link: https://doi.org/10.1016/j.exger.2025.112734
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