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Mar 19, 2025
A research team led by first author Hoang Van M. Nguyen and corresponding author Archana Unnikrishnan from the University of Oklahoma Health Sciences examined how aging impacts gut bacteria in a genetically diverse group of rats designed to reflect human-like variation. Their findings revealed that both biological sex and mitochondrial DNA genes inherited solely from mothers play a crucial role in shaping gut microbiome changes over time.
The gut microbiome a community of bacteria in the intestines influences digestion metabolism and brain function. As individuals age, these bacterial communities shift, with some changes linked to diseases like Alzheimer’s, Parkinson’s, and metabolic disorders. However, most research has focused on one sex without direct comparisons, and few studies have investigated the role of mitochondrial DNA in these age-related microbiome shifts.
To explore these factors researchers analyzed fecal samples from genetically diverse rats to examine gut bacteria composition and metabolic byproducts. They found that aging impacts gut bacteria differently in males and females, with more bacterial species changing in female rats than in males. Notably only a few microbial shifts were consistent across both sexes suggesting that men and women may experience aging differently at the microbial level, influencing nutrition and disease risk.
In male rats, five microbial species changed significantly with age, whereas nine species changed in females. Only three of these microbes showed age-related changes in both sexes.
Another major finding was that mitochondrial DNA plays a role in how gut bacteria evolve with age. These effects varied between males and females, highlighting a potential link between mitochondrial function and gut health, with important implications for aging research and personalized medicine.
Beyond studying bacteria, the researchers examined metabolic compounds like short-chain fatty acids and bile acids, which aid digestion. They found that aging influenced these compounds based on both sex and mitochondrial DNA. For instance, older female rats had higher levels of short-chain fatty acids in their feces possibly due to differences in nutrient absorption.
This study sheds light on new factors shaping the gut microbiome in aging populations. Understanding the roles of biological sex and mitochondrial DNA in these changes could pave the way for targeted strategies to maintain gut health and prevent age-related diseases. These findings emphasize the need for personalized health approaches that account for genetic and biological differences.