Fight Aging!

The gut microbiome changes with age, a collection of microbial species that live in symbiosis with their host, helping to process food. Beneficial species that generate metabolites needed by tissues decline in number, while harmful inflammatory populations grow in number. There is a bidirectional relationship between the aging of the immune system and the aging of the gut microbiome. The immune system is responsible for removing problem microbes, and when it falters in this task, the microbiome becomes more harmful to the host. In turn, problem microbes can trigger chronic inflammation, degrading immune function and tissue function. There are other issues involved in aging that negatively impact the relationship between body and microbiome, such as the declining integrity of the intestinal barrier, but immune system function is an important one.

The balance of populations in the human gut microbiome exhibits significant changes as early as mid-30s. A number of potential approaches exist to reverse these changes, some more proven and practicable than others. Fecal microbiota transplantation and flagellin immunization are probably the best of the options on the table: they are comparatively easily accomplished; there is supporting animal data; and these interventions are already tested to some degree in humans. In principle the right combination and amounts of probiotics should work, but I'm not aware of any great progress towards determining what those combinations and amounts should be, or even whether the necessary probiotics are presently manufactured at all. There is also little animal data to indicate anything more than modest benefits from present commonly used probiotics.

The small bowel microbiome changes significantly with age and aspects of the ageing process

The human gut microbiome, comprising bacteria, archaea, fungi, parasites, and viruses, has numerous, significant impacts on the physiology of the human host throughout its lifespan, including roles in nutrient absorption and metabolism, immune function, and even brain function and behavior. Following rapid colonization at birth, the gut microbiome undergoes dynamic changes during early childhood before settling into a relatively stable pattern that was thought to persist throughout adulthood, unless impacted by significant changes in diet, medications, or disease. However, recent studies have demonstrated that the gut microbiome changes with increasing age and that the diversity of the gut microbiome may influence longevity and healthy ageing.

A caveat is that these, like the majority of gut microbiome studies, relied on stool samples. Although stool is easier to procure and analyze, the small intestine is central to metabolism and the maintenance of homeostasis, and its microbial populations are significantly different from those in stool. Therefore, to explore the effects of ageing specifically on the small intestinal microbiome, we procured a total of 251 duodenal aspirates from subjects aged 18 to 80 years which had been collected as part of the REIMAGINE (Revealing the Entire Intestinal Microbiota and its Associations with the Genetic, Immunologic, and Neuroendocrine Ecosystem) study.

we demonstrate significant differences in the small intestinal microbiome in older subjects, using duodenal aspirates from 251 subjects aged 18-80 years. Differences included significantly decreased microbial diversity in older subjects, driven by increased relative abundance of phylum Proteobacteria, particularly family Enterobacteriaceae and coliform genera Escherichia and Klebsiella. Moreover, while this decreased diversity was associated with the 'ageing process' (comprising chronologic age, number of medications, and number of concomitant diseases), changes in certain taxa were found to be associated with number of medications alone (Klebsiella), number of diseases alone (Clostridium, Bilophila), or chronologic age alone (Escherichia, Lactobacillus, Enterococcus). Lastly, many taxa associated with increasing chronologic age were anaerobes.

In conclusion, this first examination of the effects of age and the ageing process on the small intestinal microbiome demonstrates that the duodenal microbiome changes with increasing age, with significant decreases in duodenal microbial diversity due to increased prevalence of phylum Proteobacteria, particularly coliforms and anaerobic taxa. Given the key roles of small intestinal microbes in nutrient absorption and host metabolism, these changes may be clinically relevant for human health during the ageing process.