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Pharmaceuticals
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Natural Products in Gut Microbiome Modulation: From Mechanisms to Clinical...
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Natural Products in Gut Microbiome Modulation: From Mechanisms to Clinical Applications

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: closed (15 June 2025) | Viewed by 1902

Special Issue Editors

Dr. Patrícia Rijo

E-Mail Website
Guest Editor
1. CBIOS Lusófona's Research Center for Biosciences and Health Technologies, Campo Grande 376, 1749-024 Lisbon, Portugal
2. Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
Interests: natural bioactive compounds; natural dermocosmetics; natural products chemistry
Special Issues, Collections and Topics in MDPI journals
Dr. Rebeca André

E-Mail Website
Guest Editor
CBIOS-Universidade Lusófona’s Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisbon, Portugal
Interests: natural products chemistry; cell metabolism; biological activities

Special Issue Information

Dear Colleagues,

In recent years, the gut microbiome has become an important point of scientific investigation due to its impact on human health. Its influence spans metabolic regulation, immune system modulation, and even mental well-being, making it an important area of ​​study. At the same time, natural bioactive compounds have drawn attention for their capacity to modulate the intestinal microbiome.

In this Special Issue, we invite researchers to submit studies on the interaction between bioactive natural products and the gut microbiome, as well as innovative approaches to harnessing natural products in microbiome-targeted therapeutic strategies.

Potential submission topics may include, but are not restricted to, the following:

  • Mechanisms of Action: elucidation of how natural products modulate the gut microbiome composition and function.
  • Biotransformation Pathways: studies on the microbial metabolism of phytochemicals and the formation of their bioactive metabolites.
  • Therapeutic Applications: study of natural products for the prevention or treatment of diseases like inflammatory bowel disease, metabolic disorders, neurodegenerative conditions, and cancer.
  • Analytical Advances: novel methods for studying microbiome–natural product interactions such as metabolomics, microbiome-targeted drug delivery, and bioinformatic approaches.
  • Clinical and Preclinical Studies: insights into the translational potential of microbiome-targeted interventions using natural compounds.

Dr. Patrícia Rijo
Dr. Rebeca André
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gut microbiome modulation
  • natural bioactive compounds
  • microbiome-targeted therapeutics
  • gut microbiome
  • human health

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Published Papers (3 papers)

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Research

32 pages, 18091 KiB  
Article
Yinchenhao Decoction Mitigates Cholestatic Liver Injury in Mice via Gut Microbiota Regulation and Activation of FXR-FGF15 Pathway
by Weiwei Li, Doudou Huang, Zichen Luo, Ting Zhou and Ziwen Jin
Pharmaceuticals 2025, 18(7), 932; https://doi.org/10.3390/ph18070932 - 20 Jun 2025
Viewed by 478
Abstract
Objective: Yinchenhao decoction (YCHD), a classical herbal formula comprising Artemisia capillaris, Gardenia jasminoides, and Rheum palmatum, has been clinically used for over 1000 years to treat cholestasis. However, its mechanism of action remains undefined. This study aimed to elucidate YCHD’s [...] Read more.
Objective: Yinchenhao decoction (YCHD), a classical herbal formula comprising Artemisia capillaris, Gardenia jasminoides, and Rheum palmatum, has been clinically used for over 1000 years to treat cholestasis. However, its mechanism of action remains undefined. This study aimed to elucidate YCHD’s therapeutic mechanisms against cholestasis, with a focus on the gut microbiota-mediated regulation of the farnesoid X receptor (FXR)–fibroblast growth factor 15 (FGF15) pathway. Methods: An alpha-naphthyl isothiocyanate (ANIT)-induced cholestasis mouse model was established. Mice received YCHD (3/9 g/kg) for 7 days. 16S rRNA sequencing, targeted LC/MS (bile acid (BA) quantification), untargeted GC/MS (fecal metabolite detection), qPCR/Western blot (FXR pathway analysis), fecal microbiota transplantation (FMT), and antibiotic depletion were employed to dissect the gut–liver axis interactions. Results: YCHD alleviated cholestatic liver injury by reducing serum biomarkers, restoring BA homeostasis via FXR-FGF15 activation, and suppressing hepatic Cyp7a1-mediated BA synthesis. It remodeled gut microbiota, enriched FXR-activating secondary BAs (CDCA, DCA, CA), and restored the intestinal barrier integrity. Antibiotic cocktail abolished YCHD’s efficacy, while FMT from YCHD-treated mice enhanced its therapeutic effects, confirming microbiota dependency. Conclusions: YCHD mitigates cholestasis through gut microbiota-driven FXR activation and direct hepatobiliary regulation. These findings bridge traditional medicine and modern pharmacology, highlighting microbiome modulation as a therapeutic strategy for cholestatic liver diseases. Full article
(This article belongs to the Special Issue Natural Products in Gut Microbiome Modulation: From Mechanisms to Clinical Applications)
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20 pages, 59852 KiB  
Article
Gut Microbiota-Targeted Intervention of Hyperlipidemia Using Monascus-Fermented Ginseng
by Qing Zhou, Cuiting Yang, Mingyue Jia, Qingsong Qu, Xinhui Peng, Weishuo Ren, Guoqing Li, Yueyang Xie, Bingxuan Li and Xinyuan Shi
Pharmaceuticals 2025, 18(5), 661; https://doi.org/10.3390/ph18050661 - 30 Apr 2025
Viewed by 449
Abstract
Background/Objectives: Hyperlipidemia (HLP) encompasses a spectrum of poorly understood lipid metabolism disorders that are frequently overlooked or misdiagnosed, potentially leading to multiple complications. While the gut microbiota has been implicated in HLP pathogenesis, the causal relationships and molecular mechanisms remain elusive. This study [...] Read more.
Background/Objectives: Hyperlipidemia (HLP) encompasses a spectrum of poorly understood lipid metabolism disorders that are frequently overlooked or misdiagnosed, potentially leading to multiple complications. While the gut microbiota has been implicated in HLP pathogenesis, the causal relationships and molecular mechanisms remain elusive. This study aimed to investigate the therapeutic mechanisms of Monascus-fermented ginseng (MFG) on HLP through gut microbiota modulation and explore treatment potential via fecal microbiota transplantation (FMT). Methods: The MFG-modulated gut microbiota was transplanted into HLP mice. Systemic evaluations, including serum biochemical parameter detection, histopathological section analysis, 16S rRNA sequencing, and fecal metabolomics, were conducted to assess therapeutic efficacy and identify associated metabolic pathways. Results: FMT significantly improved lipid profiles, reduced body weight, and attenuated hepatic lipid accumulation in HLP mice. Mechanistically, it enhanced cholesterol excretion and fatty acid β-oxidation while suppressing lipogenic regulators, concurrently promoting primary-to-secondary bile acid conversion. Gut microbiota analysis revealed that the MFG intervention effectively normalized the Firmicutes/Bacteroidetes ratio and enriched beneficial microbiota. Conclusions: These findings demonstrate FMT’s therapeutic value in HLP management and provide new perspectives on utilizing fermented herbal medicines for metabolic disorders via gut microbiota reprogramming. Full article
(This article belongs to the Special Issue Natural Products in Gut Microbiome Modulation: From Mechanisms to Clinical Applications)
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19 pages, 12057 KiB  
Article
Tuo-Min-Ding-Chuan Decoction Alleviates Asthma via Spatial Regulation of Gut Microbiota and Treg Cell Promotion
by Yanfei Hong, Zheng Yang, Zirui Liu, Na Li, Jingbo Qin, Dongyu Ge, Guiying Peng, Ji Wang and Qi Wang
Pharmaceuticals 2025, 18(5), 646; https://doi.org/10.3390/ph18050646 - 28 Apr 2025
Viewed by 611
Abstract
Objective: Tuo-Min-Ding-Chuan decoction (TMDC), a traditional Chinese prescription, has demonstrated significant clinical efficacy in treating allergic asthma. This study aimed to investigate the mechanism of TMDC in treating asthma from the perspective of Treg cells and gut microbiota across distinct gut segments [...] Read more.
Objective: Tuo-Min-Ding-Chuan decoction (TMDC), a traditional Chinese prescription, has demonstrated significant clinical efficacy in treating allergic asthma. This study aimed to investigate the mechanism of TMDC in treating asthma from the perspective of Treg cells and gut microbiota across distinct gut segments (jejunum, ileum, cecum, and colon). Methods: An ovalbumin (OVA)-induced asthma model was established in mice, followed by oral administration of TMDC at high, medium, and low dose. Immune cells and lung inflammation were examined to assess asthma severity. Microbial composition was determined by 16S rRNA sequencing. Antibiotic cocktail and Lactobacillus rhamnosus GG (LGG) were administrated to confirm the key role of specific bacteria. Results: TMDC attenuated lung inflammation (p < 0.01) and eosinophilic infiltration (p < 0.01) as well as IL-4 and IL-5 secretion (p < 0.01); it was also associated with an increase in Treg cells in the lung, small intestine (SI), and colon (p < 0.05). Meanwhile, TMDC restored the number of microbiota species and the Shannon index in the hindgut and reinstated beneficial bacteria, such as Allobaculum and Turicibacter, which were diminished in asthmatic mice. Notably, TMDC significantly enriched Bifidobacterium and Lactobacillus, particularly in the hindgut. Lactobacillus abundance was significantly correlated (p < 0.05) with Treg cells, IL-4, IL-5, and eosinophils. Furthermore, LGG supplementation restored elevated lung inflammation (p < 0.05) and decreased Treg cells (p < 0.01) due to antibiotic-induced microbiota depletion. Conclusion: TMDC alleviated asthma by promoting Treg cell expansion in a Lactobacillus-dependent manner across different gut segments, providing new insights into its therapeutic mechanisms. Full article
(This article belongs to the Special Issue Natural Products in Gut Microbiome Modulation: From Mechanisms to Clinical Applications)
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