Drug Response Diversity: A Hidden Bacterium?

Abstract

Interindividual heterogeneity in response to treatment is a real public health problem. It is a factor that can be responsible not only for ineffectiveness or fatal toxicity but also for hospitalization due to iatrogenic effects, thus increasing the cost of patient care. Several research teams have been interested in what may be at the origin of these phenomena, particularly at the genetic level and the basal activity of organs dedicated to the inactivation and elimination of drug molecules. Today, a new branch is being set up, explaining the enigmatic part that could not be explained before. Pharmacomicrobiomics attempts to investigate the interactions between bacteria, especially those in the gut, and drug response. In this review, we provide a state of the art on what this field has brought as new information and discuss the challenges that lie ahead to see the real application in clinical practice.

Early-stage Hyperglycemia-induced Gut Microbial Changes Are Partially Associated with Mechanical Allodynia in <i>db/db</i> Mice

“…In contrast to reduced microbial community abundance in 7-week-old db/db mice, the alpha diversity analyses demonstrated that neither microbiota richness nor uniformity changed in the colon and small intestine of any group which is consistent with some clinical reports that diabetes is not associated with alpha diversity indices (Chao 1, Shannon and Simpson) [17]. In diabetic animal models with long-term hyperglycemia, abundances of the bacterial genera Helicobacter and Alistipes are increased [29,30], while those of Tyzzerella, Lachnoclostridium, Anaerotruncus, Roseburia, Bacteroides, Parabacteroides, and Lactobacillus are decreased [31][32][33][34][35]. We did not observe any change in the colonic abundance of these bacteria during early-stage hyperglycemia (7-week-old), although body weight and blood glucose levels increased from 5 weeks age [13].…”

“…The effect of metformin on the gut microbiota has been widely studied in both patients and animal models. Metformin increases the abundance of colonic bacteria (e.g., Prevotellaceae_UCG-001, Roseburia, Lactobacillus and Rikenellaceae_RC9_gut_group) in diabetic and some digestive tract diseases while decreasing Helicobacter abundance [29,32,35,37]. Additionally, metformin increases Lactobacillus abundance and decreases Bacteroides abundance in the small intestine [38,39].…”

Effects of intestinal microbiota on pharmacokinetics of cyclosporine a in rats

“…Drugs affect the diversity and richness of microbiota, and microbiota also affects the pharmacology and efficacy of drugs. Pharmacomicrobiomics is an emerging field that detects the effect of microbiome alterations on drug pharmacokinetics ( ElRakaiby et al, 2014 ; Aziz et al, 2018 ; Doestzada et al, 2018 ; Panebianco et al, 2018 ; Rowland et al, 2018 ; Hannachi and Camoin-Jau, 2021 ). Previous researches suggest that intestinal microbiota had a strong modification effect on the metabolic process of drugs, but the influence of intestinal microbiota changes on drug disposition in vivo remains to be further studied ( Zimmermann et al, 2019 ).…”

Pharmacomicrobiomics and Drug–Infection Interactions: The Impact of Commensal, Symbiotic and Pathogenic Microorganisms on a Host Response to Drug Therapy

“…In the scientific community, the study of how microorganisms influence drug response has been of increasing interest in recent years. Since 2010, when the term "pharmacomicrobiomics" was coined to describe the effects of the microbiome on drug absorption, activity and toxicity, numerous research studies have been conducted on this topic [7][8][9].…”

“…The microbiome, and even dysbiosis, specifically refer to symbiotic or commensal microorganisms. It is worth mentioning that, in this context, pharmacomicrobiomics does not provide a specific definition for interactions between drugs and pathogenic microorganisms, because an infection is characterized by the invasion and proliferation of pathogenic microorganisms in body tissues [9,17,18]. As far as we know, there is no specific term like "pharmaco-infection interaction" in the current literature.…”