Microbes and Aging

The human digestive tract, primarily the colon, typically contains between 300 to 1000 different bacterial species, collectively known as our gut microbiome. Studies from the last 20 years have repeatedly shown important connections between the composition of our gut microbiome (i.e. the number of different species and the relative quantities of each species) and various aspects of our health. Not only do our indigenous flora help with food digestion, but they also protect us from pathogens, promote the development of our immune system, and even influence our brains through the production of microbial metabolites. Some of these bacterial metabolites are specific biochemicals that cannot be produced by human cells and are instead produced only by certain microbes. These bacterial metabolites are released into the gut and enter the bloodstream where they circulate to the brain and other organs. Determining what all the bacterial metabolites are, deciphering what they do, and understanding how they affect our health is a daunting task that has only begun in recent years. Complicating the analysis is the fact that humans vary greatly in their microbiome composition, and we are far from knowing how these individual variations contribute to overall health. Two studies discussed below have begun to explore connections between the microbiome and human aging.

An article published in Nature reported on a Japanese study examining the microbiome of centenarians (average age of 107) versus old (85-89 years old) and young (21-55 years old) individuals. The centenarians showed some distinct differences in their microbiomes compared to both the old and young groups. In particular, the centenarians showed enrichment of bacterial species that could modify human bile acids. When the feces of the three groups were examined, centenarians had increased levels of bile acid derivatives known as lithocholic acids (LCAs), particularly one called isoalloLCA. Studies in mice found that isoalloLCA production resulted from a family of bacteria called Odoribacteraceae, one of the bacterial types more prominent in the centenarians compared to the other two test groups. Both in the guts of mice and with human fecal bacteria, isoalloLCA was a potent growth inhibitor of many gram-positive bacteria, including the potential pathogen, Clostridium difficile. The authors speculated that the higher levels of isoalloLCA in the centenarian’s gut may be protecting them from colonization by pathogenic bacteria. They haven’t yet tested whether or not this isoalloLCA protection is contributing to a longer lifespan, but even if it isn’t, the use of this compound to treat C. difficile and other gut infections is a potentially valuable offshoot of the study.

The second Nature report is an animal study performed with mice. Aging mice develop many neurological and behavioral issues resembling those seen in older humans. This includes deficits in learning and memory, increasing anxiety, and inflammation in the brain, particularly in the hippocampi, the brain regions important for memory and learning. To examine the effects of the microbiome on aging, the researchers transplanted the fecal bacteria from young mice into old mice and compared their fecal bacterial profiles after four weeks. Before transplantation, the old and young mice had significant differences in their fecal microbiomes, while after transplantation the fecal microbiome of the old mice more closely resembled that of the young mice. Coincident with the microbiome changes, the old mice showed improved learning and memory along with reduced inflammation in their hippocampal regions. The mechanism behind this restoration of brain function in the old mice was not investigated, but the authors speculated that it likely involves metabolites released by gut bacteria. Either the normal flora in the old mice could be producing metabolites that impaired brain function or the metabolites released by the flora of young mice could be protecting the brain from adverse effects of aging. It will be exciting to determine the underlying biochemistry behind this observation, to see if it has any relevance to human aging, and to determine if human brain health can be improved through the manipulation of either our gut microbiome or critical bacterial metabolites.

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