Popular painkiller uses linked to gut microbiome shifts

Popular painkiller uses linked to gut microbiome shifts

Can everyday medications affect your body's major systems? A genetic study shows how common painkillers can reshape your gut's microbiome.

Study:Assessing the effects of common pain medications on gut microbiota composition and metabolites: Findings from a Mendelian randomization study.Photo credit: Tatiana Shepeleva/Shutterstock.com

A study published in theJournal of Medical Microbiologyshowed that long-term use of salicylic acid-based painkillers can significantly alter gut microbiota composition and circulating metabolite levels.

background

The human gut microbiota is crucial for the regulation of various physiological functions, including metabolic, immune and neurological functions. The bidirectional communication network between the gut microbiota and the brain is called the gut-brain axis and has a broad impact on overall health.

The gut-brain axis has attracted significant attention in the scientific world due to its involvement in several human diseases, including digestive, immunological and neuropsychiatric diseases.

Chronic pain is a condition of persistent discomfort that can affect a person's physical and mental health. The condition is treated primarily with analgesics, including opioids, anilides, nonsteroidal anti-inflammatory drugs (NSAIDs), and salicylic acid, which are known to cause gastrointestinal side effects.

Emerging evidence suggests that analgesics may influence the functionality of the gut-brain axis because analgesic receptors are expressed in the gastrointestinal tract and brain. Long-term use of analgesics has been found to alter the composition of gut microbiota and circulating levels of gut microbiota-derived metabolites. However, the causal relationship between these three factors remains uncertain.

Given the increasing use of analgesics and the significant influence of the gut-brain axis on human health, the current study investigated the causal relationship between common analgesics and gut microbiota.

The study

The study used the Mendelian randomization approach to determine the causal associations between genetic susceptibility to four analgesics used (NSAIDs, salicylic acid, opioids and anilides) and changes in gut microbiota composition and circulating metabolites.

The Mendelian randomization approach uses genetic variants as key variables to infer causal relationships between exposures and outcomes. This study uses analgesics and gut microbiota changes. This approach can effectively eliminate the possible bias caused by confounding factors and reverse causality.

It is important to note that this method assesses genetic predisposition to using medications as a surrogate for long-term drug exposure, rather than measuring the effects of taking these medications directly in a clinical trial.

Summary-level data on analgesics and gut microbiota were derived from genome-wide association studies involving primarily European Ancestry cohorts, including 466,457 participants from the UK Biobank and 18,340 individuals from the Mibiogen consortium.

Study results

The study reported a significant impact of salicylic acid use on the abundance of gut microbiota. In particular, salicylic acid use was associated with reduced abundance of eight microbiota traits, including genusClostridiumsensucto1PresentAdlercreeutziaPresentAkkermansiaFamilyClostridiaceae1,AndVerrucomicrobiaceaePhylum Verrucomicrobia, classVerrucomicrobiaeand orderVerrucomicrobialesand increased family fullnessPrevotellaceae.

The study found no significant impact of anilide and opioid use on gut microbiota composition. Conversely, NSAIDs only showed a causal relationship with the increased group frequencyEubacterium xylanophilum.

Regarding circulating metabolites, the study found significant causal associations of salicylic acid consumption with four metabolites, including acetoacetate, creatinine, omega-3 fatty acids and very high density lipoprotein triglycerides.

Among other analgesics tested, anilide showed potential causal associations with three metabolites (citrate, glutamine and urea), opioid with two metabolites (apolipoproteins and glucose), and NSAID with one metabolite (acetoacetate).

Investigate significance

The study identifies significant gut microbiota alteration effects of long-term salicylic acid consumption. In particular, the results suggest that salicylic acid as an analgesic drug may exert potential multi-level effects on gut microbiota composition. However, the study did not find strong associations with gut microbiota for other analgesics tested.

Regarding circulating metabolites, the study finds potential causal associations with all four analgesic classes tested. The metabolites affected by salicylic acid play a crucial role in brain glucose uptake, memory encoding, and Alzheimer's disease development. Similarly, metabolites affected by anilides and opioids are associated with the pathogenesis of Parkinson's disease, acute colitis and schizophrenia.

However, these links are not the direct effects observed in this study. They are discussed as possibilities based on the known roles of these metabolites in disease.

Overall, the study results highlight the need for future investigations to better understand the extent to which analgesics may trigger the pathogenesis of neuropsychiatric and digestive disorders through the gut-brain axis.

This study is the first of its kind to apply Mendelian randomization to evaluate the causal relationship between analgesic and gut microbiota. Multiple methods have been used to accurately produce Mendelian randomization estimates and significantly improve the robustness of observed associations.

Despite robust methods, the study has some limitations. Many factors, including diet, physical activity, and other lifestyle habits, can influence gut microbiota composition. The study analysis did not control for these confounding factors. Further research is needed to uncover the underlying mechanisms.

Furthermore, the Mendelian randomization analyzes were performed based on the assumption of linear correlation, limiting the ability to rule out a nonlinear relationship between exposure and outcome.

While these results provide evidence for possible causal relationships between certain analgesics and changes in gut microbiota and metabolites, direct clinical studies are needed to confirm these effects and clarify their clinical significance.

Download your PDF copy now!

Sources: