Mechanisms and Clinical Implications of Human Gut Microbiota-Drug Interactions in the Precision Medicine Era

Biomedicines, Journal Year: 2024, Volume and Issue: 12(1), P. 194 - 194

Published: Jan. 16, 2024

The human gut microbiota, comprising trillions of microorganisms residing in the gastrointestinal tract, has emerged as a pivotal player modulating various aspects health and disease. Recent research shed light on intricate relationship between microbiota pharmaceuticals, uncovering profound implications for drug metabolism, efficacy, safety. This review depicted landscape molecular mechanisms clinical dynamic Microbiota-Drug Interactions (MDI), with an emphasis impact MDI responses individual variations. also discussed therapeutic potential or harnessing its metabolic capabilities to optimize treatments advance personalized medicine, well challenges future directions this emerging field.

Language: Английский

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Self-emulsifying drug delivery systems (SEDDS) disrupt the gut microbiota and trigger an intestinal inflammatory response in rats

International Journal of Pharmaceutics, Journal Year: 2023, Volume and Issue: 648, P. 123614 - 123614

Published: Nov. 17, 2023

Self-emulsifying drug delivery systems (i.e. SEDDS, SMEDDS and SNEDDS) are widely employed as solubility bioavailability enhancing formulation strategies for poorly water-soluble drugs. Despite the capacity SEDDS to effectively facilitate oral absorption, tolerability concerns exist due high concentrations of surfactants (typically present within SEDDS) induce gastrointestinal toxicity mucosal irritation. With new knowledge surrounding role gut microbiota in modulating intestinal inflammation injury, there is a clear need determine impact on microbiota. The current study first its kind demonstrate detrimental Sprague-Dawley rats, following daily administration (100 mg/kg) 21 days. comprising lipid phase Type I, II III formulations according Lipid Formulation Classification Scheme) induced significant changes composition diversity microbiota, evidenced through reduction operational taxonomic units (OTUs) alpha (Shannon's index), along with statistically shifts beta (according PERMANOVA multi-dimensional Bray-Curtis plots). Key signatures dysbiosis correlated increased expression pro-inflammatory cytokines jejunum, while injury was characterised by reductions plasma citrulline levels, validated biomarker enterocyte mass barrier integrity. These findings have potential clinical ramifications chronically administered drugs that formulated stresses further studies investigate dose-dependent effects microenvironment setting.

Language: Английский

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Targeting the Gut: A Systematic Review of Specific Drug Nanocarriers

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(3), P. 431 - 431

Published: March 21, 2024

The intestine is essential for the modulation of nutrient absorption and removal waste. Gut pathologies, such as cancer, inflammatory bowel diseases (IBD), irritable syndrome (IBS), celiac disease, which extensively impact gut functions, are thus critical human health. Targeted drug delivery to tackle these diseases, improve therapy efficacy, minimize side effects. Recent strategies have taken advantage both active passive nanocarriers, designed protect until it reaches correct site modulate release via use different physical–chemical strategies. In this systematic review, we present a literature overview nanocarriers used in set chronic intestinal highlighting rationale behind controlled therapies. overall aim provide reader with useful information on current approaches targeting novel therapeutic

Language: Английский

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Inulin‐Lipid Core–Shell Microcapsules Target the Gut Microbiota and Mimic the Pharmaceutical Food Effect for Improved Oral Antipsychotic Delivery

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(40)

Published: April 25, 2024

Abstract The oral delivery of most atypical antipsychotics is severely challenged by their low bioavailability and significant food effects that necessitate patient compliance. Lipid formulations are an attractive system for overcoming the dosing challenges antipsychotics, but negative impact on gut microbiota can interfere with pharmacodynamic response through disruption gut‐brain axis. Here, novel microbiota‐targeting microcapsules engineered to provide a multifunctional approach improving both pharmacokinetic properties antipsychotic, lurasidone. comprised lipid core facilitates solubilization absorption lipophilic drug outer carbohydrate polymer (inulin) shell positively modulates facilitating microbial fermentation. Fed‐fasted variability in lurasidone mitigated microencapsulation inulin‐lipid (ILM), while enrichment coupled enhanced serotonin levels small intestine, faeces, plasma. realization ILM confirms pharmacokinetics efficacy mental health therapies, such as be optimized strategic encapsulation within functional target effective modulation

Language: Английский

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The impact of common pharmaceutical excipients on the gut microbiota

Expert Opinion on Drug Delivery, Journal Year: 2023, Volume and Issue: 20(10), P. 1297 - 1314

Published: June 12, 2023

Increasing attention is being afforded to understanding the bidirectional relationships that exist between oral medications and gut microbiota, in an attempt optimize pharmacokinetic performance mitigate unwanted side effects. While a wealth of research has investigated direct impact active pharmaceutical ingredients (APIs) on interactions inactive (i.e. excipients) microbiota are commonly overlooked, despite excipients typically representing over 90% final dosage form.Known excipient-gut for various classes ingredients, including solubilizing agents, binders, fillers, sweeteners, color additives, reviewed detail.Clear evidence indicates orally administered directly interact with microbes can either positively or negatively diversity composition. However, these mechanisms overlooked during drug formulation, potential excipient-microbiota alter pharmacokinetics interfere host metabolic health. The insights derived from this review will inform scientists necessary design considerations mitigating adverse pharmacomicrobiomic when formulating forms, ultimately providing clear avenues improving therapeutic safety efficacy.

Language: Английский

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Updated perspectives on the contribution of the microbiome to the pathogenesis of mucositis using the MASCC/ISOO framework

Supportive Care in Cancer, Journal Year: 2024, Volume and Issue: 32(8)

Published: July 30, 2024

Advances in the treatment of cancer have significantly improved mortality rates; however, this has come at a cost, with many treatments still limited by their toxic side effects. Mucositis both mouth and gastrointestinal tract is common following anti-cancer agents, manifesting as ulcerative lesions associated symptoms throughout alimentary tract. The pathogenesis mucositis was first defined 2004 Sonis, almost 20 years on, model continues to be updated reflecting ongoing research initiatives more sophisticated analytical techniques. most recent update, published Multinational Association for Supportive Care Cancer International Society Oral Oncology (MASCC/ISOO), highlights numerous co-occurring events that underpin development. Most notably, role ecosystem microorganisms reside (the oral gut microbiota) explored, building on initial concepts proposed Sonis. However, questions remain regarding true causal contribution microbiota metabolome. This review aims provide an overview rapidly evolving area, synthesizing current evidence microbiota's development progression, highlighting (i) components 5-phase where microbiome may involved, (ii) methodological challenges hindered advances (iii) opportunities intervention.

Language: Английский

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Phase IV Metabolism

Gastroenterology Clinics of North America, Journal Year: 2025, Volume and Issue: 54(2), P. 383 - 395

Published: Jan. 23, 2025

Language: Английский

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Exploring the role of gut microbiota in antibiotic resistance and prevention

Annals of Medicine, Journal Year: 2025, Volume and Issue: 57(1)

Published: March 17, 2025

Background/Introduction Antimicrobial resistance (AMR) and the evolution of multiple drug-resistant (MDR) bacteria is grave public health concern. To combat pandemic AMR, it necessary to focus on novel alternatives for drug development. Within host, interaction pathogen with microbiome plays a pivotal role in determining outcome pathogenesis. Therefore, microbiome-pathogen one potential targets be explored antimicrobials.

Language: Английский

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The Effect of Gut Microbiome Perturbation on the Bioavailability of Glycyrrhizic Acid in Rats

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(4), P. 457 - 457

Published: April 1, 2025

Background: Oral administration remains the most common route for drug absorption. Emerging evidence highlights important role of gut microbiome in pharmacokinetics oral medications. Glycyrrhizic acid (GL), a widely used hepatoprotective drug, is orally administrated and subsequently biotransformed by microbiota into its active metabolite, glycyrrhetinic (GA), which exerts therapeutic effect. However, it unclear whether disturbance directly impacts metabolism GL. Methods: Antibiotic cocktail probiotic Lacticaseibacillus rhamnosus R0011 were applied as two interventions targeting microbiome. Pharmacokinetic parameters evaluated LC-MS, 16S rRNA sequencing was to analyze composition. The transcriptome analysis Caco-2 cells elucidate regulation mechanism polar metabolites resulting from perturbation. Results: supplementation could significantly increase Area Under Curve (AUC) value GA, positively correlated with change In contrast, plasma levels GA nearly undetectable following antibiotic intervention. Furthermore, relative expressions transporter multidrug resistance gene 1 (MDR1) ileum site specifically downregulated under microbial may play crucial differentiated regulating MDR1 expression, likely through modulation transcription factors FoxO1 TP53. Conclusions: Our research provides new insights regulatory affects bioabsorption drugs, potentially offering strategies optimize bioavailability improve clinical efficacy.

Language: Английский

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Translational strategies for oral delivery of faecal microbiota transplantation

Gut, Journal Year: 2025, Volume and Issue: unknown, P. gutjnl - 335077

Published: April 29, 2025

Faecal microbiota transplantation (FMT) has emerged as a transformative therapy for Clostridioides difficile infections and shows promise various GI systemic diseases. However, the poor patient acceptability accessibility of ‘conventional’ FMT, typically administered via colonoscopies or enemas, hinders its widespread clinical adoption, particularly chronic conditions. Oral administration FMT (OralFMT) overcomes these limitations, yet faces distinct challenges, including significant capsule burden, palatability concerns microbial viability during gastric transit. This review provides comprehensive analysis emerging strategies that aim to advance OralFMT by: (1) refining processing technologies (eg, lyophilisation) enable manufacturing low-volume formulations reducing burden (2) developing delivery improve organoleptic safeguard targeted colonic release. These advancements present opportunities expand therapeutic scope, beyond C. infections, towards conditions requiring frequent dosing regimens. While this primarily focuses on optimising delivery, it is important contextualise within broader shift defined consortia. Live biotherapeutic products (LBPs) offer an alternative approach, interplay between LBPs in practice remains unresolved. We postulate continued innovation multidisciplinary approach can further increase efficacy scalability by enabling disease site targeting, co-delivery compounds overcoming colonisation resistance. Realising goals positions cornerstone personalised care across range diseases rooted microbiome health.

Language: Английский

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