The human gut microbiome is made up of a few thousand distinct microbial species. The relative sizes of these populations shift in response to day to day circumstances, such as variations in diet, but one would expect consistency from one year to the next. Over longer spans of time, the gut microbiome ages. Populations producing beneficial metabolites are reduced in number, while populations that provoke the immune system into chronic inflammatory behavior grow in number. This data is derived from both animal and human studies. One can control what happens to a mouse over the course of its life, but for human data the detailed history of any particular individual is largely a mystery.
Antibiotics and a range of other pharmaceuticals produce dramatic short-term effects on the composition of the gut microbiome. To a large degree, the gut microbiome restores itself once the pharmaceutical is no longer present. That said, we might well ask how much of the observed human data on gut microbiome aging is produced by, say, antibiotic use. Researchers have observed gut microbiome changes in population studies taking place as early as the mid-30s, and it is hard to envisage any form of meaningful degeneration taking place at that age. But exposure to antibiotics and other pharmaceuticals? That is very prevalent. In later life, given the presence of chronic diseases of aging, there is a great deal more chronic pharmaceutical use, as well as the employment of pharmaceuticals with meaningful side effects. We might again ask how much of the observed aging of the human gut microbiome at the population level results from the use of these treatments versus mechanisms of aging.
Drug-mediated disruption of the aging gut microbiota and mucosal immune system
The dynamic relationship of gut microbiota, mucosal immunity, aging, and pharmaceutics interventions has a significant impact on overall physiological functions and disease susceptibility. Aging is associated with changes in the gut microbiome including decreased microbial diversity, reduced short-chain fatty acid (SCFA) production, and elevated pathobiont proportions. These changes are associated with impaired mucosal immunity, increased intestinal permeability, and heightened systemic inflammation in the host, which can exacerbate age-related disorders.
Medications such as proton pump inhibitors (PPIs), metformin, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and antibacterials also influence gut microbiota function. PPIs may alter microbial colonies and induce overgrowth of pathogenic bacteria, which compromises the mucosal defenses and in severe cases, the resulting infections may cause ulcers. Metformin, through its metabolic benefits, causes Akkermansia muciniphila to increase in relative abundance, which is associated with improved gut barrier composition. NSAIDs, because of their strong anti-inflammatory properties, disturb gut homeostasis by increasing intestinal permeability, reducing prostaglandin synthesis, and inducing dysbiosis in the host. Corticosteroids, through their immunosuppressive mechanisms, reduce microbial diversity and secretory immunoglobulin A levels, impairing mucosal immunity and enhancing the host’s susceptibility to infections. Antibacterials are a major disruptor of the gut microbiota, causing a decline in beneficial bacteria and an increased risk for opportunistic infections such as Clostridium difficile.
To address drug-induced dysbiosis, probiotics and prebiotics products may be helpful to restore microbial balance, enhance SCFA production, and reinforce mucosal defenses. Individualized gut microbiota profiling may enable safer medication usage by identifying patients that are at an increased risk for dysbiosis-related complications. Additionally, development of microbiota-sparing medications and targeted therapies may help to enhance gut health outcomes in aging populations. Future research should address the long-term effects of pharmacological agents on gut microbiota and mucosal immunity in aging populations, as well as identification of connections between microbiota, immune function, and the effects of medications. Integrating microbiome-conscious approaches into clinical practice could allow healthcare providers to optimize patient care
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