Microbial shifts in the aging mouse gut (1)
The human microbiome influences and is influenced by several aspects of the host’s health and development. Different groups of bacteria can synthesize energy sources such as butyrate and other short-chain fatty acids, stimulate the immune system, and provide protection from pathogens through competitive exclusion and the production of protective compounds such as bacteriocins. There are many probable confounding factors in human studies, including change in diet, medications, and housing status (e.g., home residence versus long-term care facilities), making it difficult to identify direct effects of aging and frailty. Although not free of confounding factors themselves, mouse studies allow for better-controlled observations and experiments and have been shown to serve as good models of the human microbiome.
The strong correlation between frailty index (FI) scores and age reinforces that both are suitable measurements to compare with changes in the gut microbiome. Fares and Howlett showed that a 50% mortality rate occurs around 24 months in mice, which corresponds roughly to age 85 in humans.
The Rikenellaceae family was the most significantly overrepresented family within the middle and old groups in comparison to young mice when using 16S data (Kruskal-Wallis H test, Benjamini-Hochberg FDR multiple test correction p = 0.007).
Most monosaccharide utilization categories were overrepresented in the old group compared to the young and middle groups, with the complex polysaccharide-xyloglucan utilization category underrepresented in the old group (0.112% ± 0.014%, p = 0.034) compared to the middle group (0.122% ± 0.016%) There was shown to be a decline in the saccharolytic potential of microbiome with age and a limited supply of simple sugars for gut epithelium function in the old age group. Cobalamin (B12) biosynthesis was significantly underrepresented within the old group (0.037% ± 0.041%, p = 0.041) compared to the middle (0.129% ± 0.026%) and young (0.054% ± 0.018%) groups.
Elevated levels of human β-glucuronidase activity in tumors compared to normal cells led to the development of several selective cancer chemotherapeutics. However, many microbial species contain β-glucuronidase homologs, which have been shown to reactivate the cancer drug irinotecan (e.g., CPT-11) leading to severe diarrhea and thus limiting the efficacy of the drug. High fecal lactate is associated with ulcerative colitis and other inflammatory bowel diseases. The aging microbiome could have an effect on the availability of vitamins (B12 and B7) and creatine, DNA repair, and carbohydrate metabolism as well as the potential to interfere with some drug treatments. Up to 30% of the variation in the microbiome can arise from cage effects, possibly due to coprophagy. The groups of interest are housed in the same cage, or individually. However, solitary cages for the entire life of a mouse can induce high levels of stress which may in turn influence the microbiome, while a single cage for all mice is not practical for large-scale animal studies.