Age-dependent remodeling of gut microbiome and host serum metabolome in mice.

The interplay between microbiota and host metabolism plays an important role in health. Here, we examined the relationship between age, gut microbiome and host serum metabolites in male C57BL/6J mice. Fecal microbiome analysis of 3, 6, 18, and 28 months (M) old mice showed that the Firmicutes/Bacteroidetes ratio was highest in the 6M group; the decrease of Firmicutes in the older age groups suggests a reduced capacity of gut microflora to harvest energy from food. We found age-dependent increase in Proteobacteria, which may lead to altered mucus structure more susceptible to bacteria penetration and ultimately increased intestinal inflammation. Metabolomic profiling of polar serum metabolites at fed state in 3, 12, 18 and 28M mice revealed age-associated changes in metabolic cascades involved in tryptophan, purine, amino acids, and nicotinamide metabolism. Correlation analyses showed that nicotinamide decreased with age, while allantoin and guanosine, metabolites in purine metabolism, increased with age. Notably, tryptophan and its microbially derived compounds indole and indole-3-lactic acid significantly decreased with age, while kynurenine increased with age. Together, these results suggest a significant interplay between bacterial and host metabolism, and gut dysbiosis and altered microbial metabolism contribute to aging.

Emerging computational tools and models for studying gut microbiota composition and function.

The gut microbiota and its metabolites play critical roles in human health and disease. Advances in high-throughput sequencing, mass spectrometry, and other omics assay platforms have improved our ability to generate large volumes of data exploring the temporal variations in the compositions and functions of microbial communities. To elucidate mechanisms, methods and tools are needed that can rigorously model the dependencies within time-series data. Longitudinal data are often sparse and unevenly sampled, and nontrivial challenges remain in determining statistical significance, normalization across different data types, and model validation. In this review, we highlight recent developments in models and software tools for the analysis of time series microbiome and metabolome data, as well as integration of these data.