Introduction
The human gut microbiome consists of trillions of bacteria and other microorganisms living symbiotically within our bodies. As wellness professionals, we must appreciate that gut microbes play pivotal roles in shaping patient health outcomes. Many patients rely on various medications to support their immune, digestive, and mental health, but routinely prescribed medications can disrupt the microbiome’s delicate equilibrium, causing unintended health consequences. Three such medicines that have shown an impact on the gut microbiome are selective serotonin reuptake inhibitors (SSRIs), nonsteroidal anti-inflammatory drugs (NSAIDs), and antibiotics. Understanding their effect on gut health is central to getting the most of the medications that so many have come to depend on.
How SSRIs Affect the Gut
SSRIs have been shown to change the balance of bacteria in the gut. Paroxetine and escitalopram often reduce certain types of bacteria, like Firmicutes, while helping others like Bacteroidetes and Eubacterium ramulus grow. These changes have been shown to have anti-inflammatory effects in patients [2]. However, in some cases, bacteria that reduce SSRI bioavailability, such as Streptococcus salivarius, can accumulate during SSRI treatment [4]. Therefore, high levels of Streptococcus salivarius may impact medication efficacy by preventing the body from effectively processing and making use of the SSRI.
With this in mind, it's important to understand one’s gut microbiome composition before and during SSRI treatment, because this can impact how well medication works for depression. People with more of certain beneficial bacteria to start, like Faecalibacterium and Roseburia, are more likely to improve with SSRIs, while those with high levels of some harmful microbes like Proteobacteria tend to respond worse [4] . Insight into a person's unique gut microbial imbalance could guide which antidepressant may work best for them.
This means that strategically altering the gut microbiome could improve SSRI efficacy. For example, compounds like sodium butyrate that restore microbial balance can reduce side effects and improve SSRI response [4]. Combining probiotics like Lactobacillus and Bifidobacterium with fibers that they feed on, called synbiotics, can enhance the positive effects of SSRIs [2]. Lastly, diet changes, custom nutrition plans, or patient-specific probiotic cocktails matched to someone's specific dysbiosis patterns may optimize such microbiome-mediated antidepressant boosts [4].
Growing evidence shows gut microbes and SSRIs significantly influence each other, shaping how well medication treats depression. Continued research on how microbiomes change long-term with SSRIs could support efforts to personalize and improve pharmacotherapy via microbiome-targeted products.
NSAIDs and the Microbiome
Several studies in animals and humans demonstrate that NSAID administration causes significant changes in the composition and function of the gut microbiota. NSAIDs can have direct antibacterial effects, while also altering the gut environment in ways that precipitate dysbiosis. Specifically, NSAIDs are associated with decreased abundance of bacteria from the Firmicutes phylum and increased proportions of Bacteroidetes and Proteobacteria species [1]. These shifts favor Gram-negative and anaerobic bacteria implicated in intestinal inflammation and damage [1]. If untreated, chronic intestinal inflammation can result in diarrhea, abdominal pain, and rapid weight loss, which are symptoms commonly found in patients struggling with IBD and Crohn’s Disease [7].
A substantial overlap exists between the microbial changes caused by NSAIDs and the dysbioses linked to the diseases that these drugs treat - like spondyloarthritis, rheumatoid arthritis, and diabetic neuropathic pain. For example, both NSAIDs and opioids increase Prevotella, which has been shown to positively correlate with rheumatoid arthritis severity [3]. Thus, long-term use of these medications may actually contribute to disease persistence or limit efficacy by promoting inflammation-causing microbial blooms [1].
The NSAID-microbiome relationship is complex. Making it important to understand the causes and consequences of drug-induced dysbiosis, and its role in efficacy and disease progression. Especially when considering prescribing NSAIDs to patients.
Antibiotics: The Microbiome Double-Edged Sword
Like SSRIs and NSAIDs, substantial evidence shows that antibiotics significantly disrupt the gut microbiome, inducing dysbiosis [5]. Both clinical and animal studies demonstrate altered microbial compositions post-antibiotic exposure [5]. Short-term antibiotic use decimates beneficial bacteria populations such as Bifidobacterium and Lactobacillus. Simultaneously, pathogens like Clostridium difficile and Salmonella have been shown to flourish in the disrupted ecosystem [6]. Antibiotics also negatively impact gut-brain communication through multiple mechanisms - including reduced bacterial production of neurotransmitters like GABA and serotonin, decreased expression of brain-derived neurotrophic factor, blood-brain barrier compromisation, and inflammatory pathway activation [5]. Interestingly, these alterations persist for weeks or years after stopping antibiotics [6]; resulting in dysbiosis that disturbs the microbiome’s contributions to metabolism, immunity, and colonization resistance [6].
In addition to ecological damage, antibiotics promote antibiotic resistance through horizontal gene transfer between gut bacteria [6]. Resistant strains and genes continue spreading to other microbes even after antibiotic clearance. This expanding antibiotic resistome threatens to limit viable infection treatment options over time. Antibiotic-induced dysbiosis also appears to reduce efficacy of medications reliant on bacterial enzymes for activation or metabolism [6].
Additional research is required to pinpoint the precise impacts of antibiotic-induced taxonomic shifts [5]. For example, comparative analyses could also determine which antibiotic classes most severely impact beneficial nutrient and neurotransmitter-producing bacteria. Deepening our grasp of how antibiotics influence microbial functionality and host physiology is key to developing microbiome-targeted therapies that mitigate unintended antibiotic side effects.
Conclusion
Accumulating research reveals the pervasive impacts of widely prescribed SSRIs, NSAIDs and antibiotics on intestinal microbes - often eliciting negative health consequences. These studies spotlight the microbiome’s extensive interconnected role in physiological processes, constituting an extremely delicate ecosystem that is easily disrupted yet not easily rebalanced.
Going forward, illuminating intricate drug-microbiome-host dynamics should improve pharmacotherapy and patient wellness. As health professionals, continuing education on scientific discoveries can help recognize and potentially redress medication-induced microbial disruptions. Understanding the effect prescription medications can have on the gut microbiome will help us maximize their positive impact in the patients who rely on them, while minimizing potential negative side effects. If you are a health professional interested in learning more about how treatment mechanisms can impact your patients, visit our Shop to explore our tests which will provide increased insight into your patient’s gut health. Connect with GutChat, our dedicated gut-health AI ChatBot, or reach out directly to a team member at info@injoy.bio to get started on leveling up your care.
Sources
- https://www.frontiersin.org/articles/10.3389/fphar.2020.01153/full
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295378/
- https://www.sciencedirect.com/science/article/pii/S0163725822002212?via%3Dihub
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051028/
- https://www.sciencedirect.com/science/article/abs/pii/S0165178119303701
- https://onlinelibrary.wiley.com/doi/10.1002/mbo3.1260
- https://www.gastrojournal.org/article/S0016-5085(04)00461-5/fulltext
