Editorial: Rodent model organisms: Therapeutic treatments and drugs interaction with the gut microbiome

Eugenia Bezirtzoglou ¹ Julio Plaza-Diaz ² Jiajia Song ³ Guoxiang Xie ⁴ Elisavet Stavropoulou ^1*

• ¹ Medical School, Democritus University of Thrace, Alexandroupolis, Greece
• ² International University of La Rioja, Logroño, La Rioja, Spain
• ³ Southwest University, Chongqing, Chongqing Municipality, China
• ⁴ Human Metabolomics Institute, Shenzhen, China

Despite progress in microbiome research, challenges still remain, as microbiomes depend on many factors, such as diet, genetics, lifestyle, and environment (Dong and Gupta, 2019).Rodent model organisms, notably mice and rats, are widely used in microbiome research to investigate therapeutic applications and drug interactions within the gut ecosystem (Vandamme, 2014).Microbiome research is often conducted on rodents rather than humans for several paramount reasons. Research on rodents permits research in a regulated and controlled setting excluding specific factors. Rodents have short lifespans and reproduce quickly. Yet, they show physiological and genetic similarities with humans, making them ideal models for investigating immune responses, metabolic diseases and drug interactions. This is compared to human clinical studies that require long-term monitoring and ethical considerations (Vandamme, 2014;Bryda, 2013).In this vein, the present Research Topic focuses on publishing research that explores microbial ecosystems within vertebrates' digestive tracts.Researchers have conducted numerous studies to improve understanding of the field. Certainly, advancements in sequencing technologies, including metagenomics and 16S rRNA sequencing, have enabled scientists to study microbiomes with unprecedented precision. These innovative methods facilitate microbial identification, their genetic functions, and interconnections within ecosystems (Satam et al., 2023;Kim et al., 2024).The present topic outlines studies that disrupt microbial composition, leading to dysbiosis and inflammation as well as metabolic disorders.Extended research into natural products, probiotics and prebiotics was done in China with rodent models to evaluate their role in restoring microbial balance. Traditional natural products , such as Gynura segetum root (GSrE) (Gu et al., 2022), tuina herbal (Wang et al., 2023), Sanwei sandalwood (Ma et al., 2023), Ziyan green tea (Jia et al., 2023), Scrophulariae radix-Atractylodes sinensis (Guo et al., 2022), Sheng-Jiang powder (Zhang et al., 2024), Banxia-Yiyiren (Wang et al., 2024), Gegen Qinlian (Xu et al., 2024), Liquiritigenin (Suo et al., 2024), Xiaojin Pill (Yang et al., 2024), Schisanlactone (Song et al., 2024), Liqi Tongbian (Liu et al., 2024), Shengu granules (Chen et al., 2024), Evodiae fructus (Liang et al., 2024), Bazi Bushen (Zhang et al., 2024) were excessively studied in rodent models. Traditional Chinese medicine (TCM) shows increasing interest in microbiome research impacting beneficially on multiple diseases through microbiome modulation. These TCM herbal formulations may treat metabolic disorders, gastrointestinal inflammatory diseases, autoimmune diseases, and mental and neurological conditions. They do so by modulating the microbial balance, relieving inflammation, and boosting immune function. Yet, fermentation-based TCM formulations providing bioactive substances contribute effectively to modulating the microbial balance and improving the microbiome. TCM affects intestinal and extraintestinal tissues (Suo et al., 2024). It protects against pathogens by boosting immune cell function and inflammatory responses.Yet, it is used to relieve insomnia, reduce stress and ease anxiety, demonstrating an antidepressant effect through its influence on the gut-brain axis (Wang et al., 2024). The microbiome-gut-brain axis may also be involved in the pathogenesis and progression of central aging-related diseases while it seems to have a key role in Alzheimer's disease (Song et al., 2024).TCM treats benign prostatic hyperplasia (Yang et al., 2024), periodontitis (Guo et al., 2023) and colonic cancer by suppressing chronic inflammation (Yang et al., 2024). Similarly, TCM helps ameliorate nonalcoholic fatty liver disease by alleviating inflammation, regulating lipid metabolism, reducing oxidative stress, and restoring gut microbiome balance, ultimately supporting liver health and improving insulin sensitivity (Zhang et al., 2024;Zaparte et al., 2024). Yet, chronic jet lag alters the gut microbiome and mycobiome and promotes metabolic dysfunction-associated fatty liver disease in high fat and high fructose diet-fed mice (Zheng et al., 2023).TCM also plays a significant role in managing diabetes by alleviating inflammation, regulating blood glucose levels, improving insulin sensitivity, and balancing the gut microbiome (Hou et al., 2025). Single-anastomosis duodenal-ileal bypass with sleeve gastrectomy seems to modify gut microbiome composition and thus glucose metabolism in rats with type 2 diabetes (Wang et al., 2024). Metformin has been linked to shifts in gut bacteria, notably increasing Akkermansia muciniphila and short-chain fatty acid-producing bacteria. These changes help stabilize the gastrointestinal mucosal barrier, regulate bile acid metabolism, and support glucose and lipid metabolism, improving glucose homeostasis and reducing inflammation (Wang et al., 2024).TCM is clearly involved in the treatment of cardiometabolic diseases, and contributes to heart failure management by improving gut microbiome function, reducing inflammation, enhancing nutrient absorption, and restoring microbial balance (Wang et al., 2024). By modulating the gut-heart axis, TCM formulations help regulate metabolism, regulate blood pressure, improve lipid metabolism, strengthen cardiac function, and mitigate disease progression (Wang et al., 2024). Additionally, gut ecological dysregulation seems to be associated with Sugen5416/hypoxia-induced disease development (Abudukeremu et al., 2024). Ang1-7 and MLN-4760 have a key role in this pathology's progression. The ACE2-Ang-(1-7)-Mas axis modulates blood pressure and inhibits myocardial remodeling (Abudukeremu et al., 2024).TCM is used in the management of osteoporosis following ovariectomy by promoting bone health, balancing hormones, and improving circulation by modulating the gut-bone immune axis (Chen et al., 2024).However, there are concerns about the potential toxicity of TCM due to the concentration of active compounds and the risk of hepatotoxicity (Suo et al., 2024;Liang et al., 2024). Some herbs, when used inappropriately or in excessive amounts, can cause liver damage or interact negatively with other medications. It is imperative to monitor the dosage, quality, and source of herbal preparations, as well as consult with healthcare providers. This is to ensure safe and effective use. The intestinal microbiome may play a role in various pathophysiological processes in diabetic ischemic heart failure. This is done by disrupting metabolism and influencing downstream signaling pathways through their metabolites. These gut microbiome and serum metabolites can serve as markers for myocardial damage in different stages of diabetic ischemic heart failure (Hou et al., 2025;Wang et al., 2024).TCM has shown a positive effect on conditions such as inflammatory diseases (López-Cauce et al., 2023) and slow-transit constipation (Liu et al., 2024) as several TCM formulations reduce inflammation, regulate bowel movements, and balance the digestive system relieving symptoms such as abdominal pain and diarrhea. Yet, Akkermansia deficiency and mucin depletion are implicated in intestinal barrier dysfunction as early events in inflammation development in interleukin-10-deficient mice (López-Cauce et al., 2023).Electroacupuncture is an advanced variation of traditional acupuncture (Yue et al., 2025), where small electrical currents are passed through acupuncture needles for therapeutic purposes. It is used to treat chronic pain, muscle tension, stress, digestive diseases, diabetes (Yue et al., 2025), and neurological disorders, as electrical boosting improves vascular angiogenesis (Huang et al., 2023), blood flow (Huang et al., 2023), reduces inflammation (Huang et al., 2023), regulates the nervous system for pain relief, but also seems to modify the urinary metabolome and microbiome (Gao et al., 2023).Oxygen is a key component of the air we breathe and plays a critical role in cellular respiration. Research explores the positive effects of oxygen enrichment on gut microbiome structure and composition in animals subjected to acute hypobaric hypoxia (Ma et al., 2023).Probiotics and prebiotics are also tested in rodent models to evaluate their role in restoring microbial balance. The alleviating effect of Lactobacillus rhamnosus SDSP202418 on exercise-induced fatigue in mice is reported (Yang et al., 2024) while the protective effects of Lactococcus lactis subsp. lactis HFY14 supplementation seems to impact positively on the brain, intestines, and motor function of antibiotic-treated mice (Yang et al., 2024). Yet, a study on the effect and mechanism of Lacticaseibacillus rhamnosus AFY06 on inflammation-associated colorectal cancer induced by azoxymethane/dextran sulfate sodium in mice gave promising results (Zhang et al., 2024).Heat acclimation with probiotics-based oral rehydration salts supplementation alleviates heat strokeinduced multiple organ dysfunction via improving intestinal thermotolerance and modulating gut microbiome in rats (Li et al., 2024).Dysfunctions in intestinal microorganisms and enzyme activities suggest potential involvement in diarrhea in kidney-yang deficiency syndrome. Specifically, a decrease in Lactobacillus and Bifidobacterium was noted, associated with an increase in Escherichia coli (Zhou et al., 2024).Another round of manuscripts addressed the gut microbiome's influence on drug metabolism. Microbes can enhance, diminish, or alter a drug's effectiveness, potentially leading to unexpected side effects. These insights contribute to refining drug development and advancing personalized treatment strategies (Wang et al., 2024;Wang et al., 2024). Folic acid and zinc ameliorate hyperuricemia by inhibiting uric acid biosynthesis and stimulating uric acid excretion by modulating the gut microbiome. Thus, folic acid and zinc may be new and safe therapeutic agents to improve hyperuricemia (Sun et al., 2022).Research findings identify the preferential distribution of transcription factor EB in colonic epithelial cells, where transcription factor EB can be activated by infection to enhance anti-bacterial peptide expression, holding promising implications for anti-bacterial therapeutics (Rao et al., 2024). The transcription factor EB has significant implications for drug metabolism, particularly in the colon, where microbial interactions influence drug bioavailability and therapeutic outcomes (Rao et al., 2024).Cathelicidin-related antimicrobial peptide plays a critical role in innate immunity and gut homeostasis. Recent research has uncovered its therapeutic potential in alleviating acute ulcerative colitis (Jiang et al., 2024).Recent research has emphasized the significant role of intestinal microorganisms and enzyme activity in kidney-yang deficiency syndrome, particularly in contributing to clinical symptoms like diarrhea. (Zhou et al., 2024).Sigma-1 knockout disrupts the gut microbiome and serum metabolome, leading to altered metabolic pathways that exacerbate heart failure. By influencing key metabolic processes and increasing systemic inflammation, this disruption worsens cardiac function (Yang et al., 2023). Targeting metabolism, particularly through restoring gut microbiome balance and regulating metabolic pathways, could offer potential therapeutic strategies for mitigating heart failure in Sigmar1-deficient models (Yang et al., 2023).Gut microbes regulate the expression of key metabolic enzymes and transporters such as CYP3A1, UGT1A1, and P-GP, all of which are involved in Cyclosporine A absorption and clearance thereby influencing its pharmacokinetic profile (Zhou et al., 2022). Research involving rodent models has revealed that broad-spectrum antibiotics can severely alter microbial diversity, resulting in dysbiosis, heightened vulnerability to infections, and the development of metabolic imbalances (Parodi et al., 2022).As already discussed, dietary choices can directly influence the composition and activity of the gut microbiome. Both food intake and fasting influence the gut's metabolic processes, immune function, and even the ability to resist infections, highlighting the critical role of diet and fasting in shaping microbiome health (Dong and Gupta, 2019;Frias et al., 2023).In conclusion, rodent model organisms have proven invaluable in advancing our understanding of the complex interactions between the gut microbiome and various therapeutic therapies. These models have facilitated significant insights into how microbial ecosystems influence drug metabolism, immune responses, metabolic diseases, and the progression of various conditions. Research has highlighted the substantial impact the gut microbiome can have on drugs pharmacokinetics, such as Cyclosporine A. It has also highlighted that modifying specific microbial communities can significantly impact drug efficacy and patient outcomes. Furthermore, traditional medicine, especially within the context of TCM, offers promising therapeutic approaches that modulate the gut microbiome for the management of metabolic disorders, autoimmune diseases, and even neurodegenerative conditions, further emphasizing the importance of gut health.Although promising, challenges remain in understanding the full scope of microbial contributions to drug metabolism and disease progression. The need for further research to fully uncover the underlying mechanisms is critical. Furthermore, potential risks associated with microbiome-based therapies, including toxicity and drug interactions, must be carefully addressed to ensure safe and effective applications in clinical settings. Ultimately, the gut microbiome represents a central area of research with transformative potential in personalized medicine. It offers new strategies to optimize therapeutic interventions and improve patient health outcomes.