Pigs as a Model to Explore Links Between the Gut Microbiome and Chronic Inflammation in Aging

The gut microbiome changes with age for reasons yet to be fully explored, but which most likely involves the age-related decline of the immune system. Research suggests a bidirectional relationship between immune aging and changes in the balance of microbial populations found in the intestines. The immune system is responsible for gardening the gut microbiome, removing unwanted microbes, but its capacity to do so declines with age. A growth in problematic microbial populations can produce disruptive, pro-inflammatory metabolites that provoke the immune system into a state of chronic inflammation, as well as invasion of tissue and bloodstream by microbes as the intestinal barrier becomes leaky.

Given that there are ways to adjust the microbial populations of the intestine into a more youthful configuration, well-established in animal models, this seems a very feasible approach to improve late life health. The treatment with the greatest amount of data is fecal microbiota transplantation from a young individual to an old individual. This class of therapy is already used in the clinic to treat severe forms of dysbiosis, and some data exists for use in old humans, in addition to the sizable body of work in old animals. Self-experimenters can readily source stool samples from young donors, and many do so. Bringing this to the clinic and widespread use would be comparatively straightforward, other than the usual problem in such cases, which is that none of the entities with deep enough pockets to fund the necessary clinical trials for FDA approval have any interest in treatments that cannot be restricted, patented, and monopolized.

Still, research continues. Beyond the existing approaches such as fecal microbiota transplant, it may be that research will give rise to much more sophisticated forms of probiotic treatment that can be restricted, patented, and monopolized, given the complexity involved. One can imagine a probiotic equivalent of fecal microbiota transplantation, in which the necessary mix of microbes is cultured rather than harvested. That would likely require advances in the process technologies involved in producing microbes in bulk quantities in order to be cost effective for mixes of hundreds of different species. Those advances could form the basis for a business funded to the level needed to conduct clinical trials and gain approval for use.

Multi-omics analysis reveals substantial linkages between the oral-gut microbiomes and inflamm-aging molecules in elderly pigs

Altered gut microbiome and host metabolism have been implicated in the process of aging. Aging is associated with changes in the gut microbiota, which in turn can affect host metabolism. The gut microbiota is a complex community of microorganisms that live in the gastrointestinal tract and play an important role in maintaining human health. As we age, the diversity and composition of the gut microbiota can change, with a decrease in beneficial bacteria and an increase in harmful bacteria. These changes in the gut microbiota can contribute to a number of age-related health problems, such as impaired immune function, inflammation, and metabolic dysfunction. For example, alterations in the gut microbiota have been linked to age-related diseases such as type 2 diabetes, cardiovascular disease, and cognitive decline.

The gut microbiome plays a critical role in host metabolism through a variety of mechanisms, including fermentation of dietary fibers, regulation of intestinal barrier function, regulation of immune function and bile acid metabolism, for instance, microbial derived short-chain fatty acids (SCFAs) can modulate various metabolic pathways in the host, including glucose metabolism and lipid metabolism, and can also affect immune function and inflammation. Overall, the relationship between the gut microbiota and host metabolism is complex and their joint action on aging still not fully understood. However, there is growing evidence to suggest that interventions aimed at modulating the gut microbiota, such as dietary changes or probiotics, may have potential therapeutic benefits for age-related metabolic disorders.

Hence, a well-controlled model system that reproduces faithfully the trajectories in the oral and gut microbiota with age is warranted and will provide a better understanding of the role played by them in the healthy development and aging of the host. Pigs are used as an excellent model to study the interaction between host microbiome and aging by combining multi-omics, because pigs share many similarities with humans in terms of their anatomy, physiology, and nutritional requirements. For example, the structure and function of the pig gut is similar to that of humans, as well as in organ development and disease progression. In addition, swine can be raised in a controlled environment and are readily available and relatively inexpensive compared to other animal models, which allows researchers to manipulate their diet and other environmental factors that may influence the host microbiome and aging process. Previous research has also been identified that pigs have a gut microbiome that is similar in composition to that of humans, with a high degree of microbial diversity and similar microbial taxa.

This study employed a comprehensive metagenomic analysis encompassing saliva and stool samples obtained from 45 pigs representing three distinct age groups, alongside serum metabolomics and lipidomics profiling. Our findings unveiled discernible modifications in the gut and oral microbiomes, serum metabolome, and lipidome at each age stage. Specifically, we identified 87 microbial species in stool samples and 68 in saliva samples that demonstrated significant age-related changes. Notably, 13 species in stool, including Clostridiales bacterium, Lactobacillus johnsonii, and Oscillibacter spp., exhibited age-dependent alterations, while 15 salivary species, such as Corynebacterium xerosis, Staphylococcus sciuri, and Prevotella intermedia, displayed an increase with senescence, accompanied by a notable enrichment of pathogenic organisms. Concomitant with these gut-oral microbiota changes were functional modifications observed in pathways such as cell growth and death (necroptosis), bacterial infection disease, and aging (longevity regulating pathway) throughout the aging process. Moreover, our metabolomics and lipidomics analyses unveiled the accumulation of inflammatory metabolites or the depletion of beneficial metabolites and lipids as aging progressed.