Our gut microbiome plays critical roles in health and disease. While our health typically deteriorates with age, the microbiome’s role in this process is not understood. Microbiome imbalances can develop with age, contributing to health issues. Research shows that taking microbes from young mice and placing them in the gut of old mice can reduce their aging markers and improve health. However, it has been difficult to pinpoint specific changes in younger or older microbiomes that could be used as therapeutic targets. Part of the difficulty lies in the variability in humans’ microbiomes, making it challenging to find trends. Read More
To address this, Rebecca Choi, Michael Shapira and their colleagues at the University of California at Berkeley examined the relationship between the microbiome and aging using a different creature, called C. elegans – a tiny worm common in terrestrial environments. These worms are an ideal model to study the microbiome, as hundreds to thousands of genetically identical worms can be studied across their short lifetime of about 3 weeks.
By examining worms that aged in compost environments, Choi and colleagues found that aging worms experienced declines in bacterial diversity. In conjunction, members of one particular bacterial family, the Enterobacteriaceae, which is also found in humans, increased in abundance. This increase was not due the cumulative exposure to these bacteria over time, nor was it influenced by environmental abundance. Instead, the increase in Enterobacteriaceae was related to changes in the gut and a decline in BMP signalling, suggesting that aging was the main factor affecting these shifts.
By studying a representative member of the Enterobacteriaceae family, the team demonstrated its potential for detrimental effects in aging animals. While this representative strain protected young adult worms from infection, its bloom in aging worms increased their susceptibility to the same infection.
The DBL1 BMP signalling pathway, which regulates immunity and controls gut bacterial abundance (and exists also in humans) declined as the worms aged. This decline may have allowed the Enterobacteriaceae bloom to arise. Using genetic tools to boost DBL1 BMP signalling helped to reduce the bloom, as well as infection susceptibility, but only partially.
The researchers then investigated whether introducing additional bacteria isolated from the gut of young worms, known as commensals, could mitigate the detrimental effects of the Enterobacteriaceae bloom. They tested small communities of commensal strains, all previously isolated from the worm gut, in different combinations. All were found to be effective in reducing aging worms’ infection susceptibility caused by the Enterobacteriaceae bloom. This finding highlights the importance of maintaining a diverse microbiome into old age.
The team’s experiments provide new insights into the relationship between aging and our microbiome. With further research, scientists may be able to leverage the microbiome to promote health into old age.
