Effects of intestinal flora on pharmacokinetics and pharmacodynamics of drugs

Džidić-Krivić, Amina; Kusturica, Jasna; Sher, Farooq; Selak, Nejra; Osmančević, Nejra; Farhat, Esma Karahmet; Sher, Farooq

doi:10.1080/03602532.2023.2186313

Cited by 17 publications

(6 citation statements)

References 63 publications

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“…It is widely accepted that gut microbes play a vital part in maintaining intestinal balance [49] and are closely related to human health or disease pathogenesis [50]. It had been reported that IBD was frequently linked with a reduction of bacterial diversity, an alteration of the gut microbiota, a drop in Firmicutes [51], and a rise in Proteobacteria [52].…”

Section: Discussionmentioning

confidence: 99%

Effect of Extracelluar Vesicles Derived from Akkermansia muciniphila on Intestinal Barrier in Colitis Mice

Zheng,

Hao,

Liu

et al. 2023

Nutrients

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Inflammatory bowel disease (IBD) is a chronic and recurrent disease. It has been observed that the incidence and prevalence of IBD are increasing, which consequently raises the risk of developing colon cancer. Recently, the regulation of the intestinal barrier by probiotics has become an effective treatment for colitis. Akkermansia muciniphila-derived extracellular vesicles (Akk EVs) are nano-vesicles that contain multiple bioactive macromolecules with the potential to modulate the intestinal barrier. In this study, we used ultrafiltration in conjunction with high-speed centrifugation to extract Akk EVs. A lipopolysaccharide (LPS)-induced RAW264.7 cell model was established to assess the anti-inflammatory effects of Akk EVs. It was found that Akk EVs were able to be absorbed by RAW264.7 cells and significantly reduce the expression of nitric oxide (NO), TNF-α, and IL-1β (p < 0.05). We explored the preventative effects on colitis and the regulating effects on the intestinal barrier using a mouse colitis model caused by dextran sulfate sodium (DSS). The findings demonstrated that Akk EVs effectively prevented colitis symptoms and reduced colonic tissue injury. Additionally, Akk EVs significantly enhanced the effectiveness of the intestinal barrier by elevating the expression of MUC2 (0.53 ± 0.07), improving mucus integrity, and reducing intestinal permeability (p < 0.05). Moreover, Akk EVs increased the proportion of the beneficial bacteria Firmicutes (33.01 ± 0.09%) and downregulated the proportion of the harmful bacteria Proteobacteria (0.32 ± 0.27%). These findings suggest that Akk EVs possess the ability to regulate immune responses, protect intestinal barriers, and modulate the gut microbiota. The research presents a potential intervention approach for Akk EVs to prevent colitis.

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Section: Discussionmentioning

confidence: 99%

Effect of Extracelluar Vesicles Derived from Akkermansia muciniphila on Intestinal Barrier in Colitis Mice

Zheng,

Hao,

Liu

et al. 2023

Nutrients

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“…The large microbial community in the intestine plays an important and complex role in drug absorption and health status of the liver. Most natural herbs, including EF, are administered orally, and intestinal microbiota first contacts the drug ingredients after entering the intestine (Džidić-Krivić et al, 2023). Intestinal ecological imbalance can indirectly or directly regulate the progress of renal diseases, among which the changes in the abundance and proportion of intestinal Bacteroidetes and Firmicutes can reflect renal diseases.…”

Section: The Influence Of Processing Factors On Ef Regulation Of Inte...mentioning

confidence: 99%

Toxicity evaluation of processing Evodiae fructus based on intestinal microbiota

Liang,

Liu,

et al. 2024

Front. Microbiol.

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BackgroundWith the development of healthcare services, drug efficacy, and safety have become the focus of drug use, and processing alters drug toxicity and efficacy, exploring the effects of processing on Evodiae fructus (EF) can guide the clinical use of drugs.MethodsFifty male Kunming mice were randomly divided into the control group (CCN), raw small-flowered EF group (CRSEF), raw medium-flowered EF group (CRMEF), processing small-flowered EF group (CPSEF), and processing medium-flowered EF group (CPMEF). The CRSEF, CRMEF, CPSEF, and CPMEF groups were gavaged with aqueous extracts of raw small-flowered EF dry paste (RSEF), medium-flowered EF dry paste (RMEF), processing small-flowered EF dry paste (PSEF) and processing medium-flowered EF dry paste (PMEF), respectively, for 21 days at 5 times the pharmacopeial dosage. Upon concluding the experiment, histopathological sections of liver and kidney tissues were examined. Additionally, levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine (SCr), and blood urea nitrogen (BUN) were determined. DNA from the intestinal contents of the mice was extracted, and 16S rRNA full-length high-throughput sequencing was performed.ResultsAfter fed EF 21 days, mice exhibited a decreasing trend in body weight. Comparative analysis with the CCN group revealed an upward trend in SCr, BUN, AST, and ALT levels in both CRSEF and CRMEF groups. The CRMEF group displayed notably elevated BUN and AST levels, with an observed increasing trend in Scr and ALT. Kidney sections unveiled cellular edema and considerable inflammatory cell infiltrates, whereas significant liver damage was not evident. Compared with CRSEF, Bun levels were significantly lower while AST levels were significantly higher in the CPMEF group. Additionally, the intestinal microbiota diversity and the relative abundance of Psychrobacter decreased significantly, and the relative abundance of Staphylococcus, Jeotgalicoccus, and Salinicoccus increased significantly in the CPMEF group. AST, ALT, and SCr were positively correlated with Staphylococcus, Jeotgalicoccus, and Salinicoccus.ConclusionIn conclusion, PMEF significantly increased harmful bacteria (Staphylococcus, Jeotgalicoccus, and Salinicoccu) and decreased beneficial bacteria. SEF with 5 times the clinical dose showed nephrotoxicity and SEF nephrotoxicity decreased after processing, but EF hepatotoxicity was not significant, which may be due to insufficient dose concentration and time.

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“…Several studies have indicated that medications can significantly affect the gut microbiota, thus playing a pivotal role in disease development and therapy [ 85 , 88 , 89 ]. At the same time, gut microbes are implicated in drug pharmacokinetics [ 90 ], pinpointing this as one of the most challenging aspects of developing individual-specific anticancer agents to improve therapeutic outcomes. Surprisingly, the role of the gut microbiota in CRC therapy is rather supported by conflicting results.…”

Section: The Role Of Gut Microbiota In Crc Development and Treatmentmentioning

confidence: 99%

“…However, it commonly causes severe diarrhea upon its conversion into the active metabolic form by microbial β-glucuronidase enzymes. Those side effects are mitigated via the utilization of β-glucuronidase inhibitors [ 90 ]. Additionally, 5-Fluorouracil (5-FU) was found to inhibit the growth of CRC-related F. nucleatum , while specific intratumoral microbiota members can covert 5-FU into a nontoxic form, thus resulting in increased cancer epithelial cell growth [ 91 ].…”

Section: The Role Of Gut Microbiota In Crc Development and Treatmentmentioning

confidence: 99%

Probiotic-Derived Bioactive Compounds in Colorectal Cancer Treatment

Thoda

Touraki

2023

Microorganisms

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Colorectal cancer (CRC) is a multifactorial disease with increased morbidity and mortality rates globally. Despite advanced chemotherapeutic approaches for the treatment of CRC, low survival rates due to the regular occurrence of drug resistance and deleterious side effects render the need for alternative anticancer agents imperative. Accumulating evidence supports that gut microbiota imbalance precedes the establishment of carcinogenesis, subsequently contributing to cancer progression and response to anticancer therapy. Manipulation of the gut microbiota composition via the administration of probiotic-derived bioactive compounds has gradually attained the interest of scientific communities as a novel therapeutic strategy for CRC. These compounds encompass miscellaneous metabolic secreted products of probiotics, including bacteriocins, short-chain fatty acids (SCFAs), lactate, exopolysaccharides (EPSs), biosurfactants, and bacterial peptides, with profound anti-inflammatory and antiproliferative properties. This review provides a classification of postbiotic types and a comprehensive summary of the current state of research on their biological role against CRC. It also describes how their intricate interaction with the gut microbiota regulates the proper function of the intestinal barrier, thus eliminating gut dysbiosis and CRC development. Finally, it discusses the future perspectives in precision-medicine approaches as well as the challenges of their synthesis and optimization of administration in clinical studies.

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Effects of intestinal flora on pharmacokinetics and pharmacodynamics of drugs

Cited by 17 publications

References 63 publications

Effect of Extracelluar Vesicles Derived from Akkermansia muciniphila on Intestinal Barrier in Colitis Mice

Effect of Extracelluar Vesicles Derived from Akkermansia muciniphila on Intestinal Barrier in Colitis Mice

Toxicity evaluation of processing Evodiae fructus based on intestinal microbiota

Probiotic-Derived Bioactive Compounds in Colorectal Cancer Treatment

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