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Gut Microbiota in Gastroenterology and Hepatology 2.0
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Gut Microbiota in Gastroenterology and Hepatology 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (15 March 2024) | Viewed by 9809

Special Issue Editor

Prof. Dr. Tzung-Yan Lee

E-Mail Website
Guest Editor
Graduate Institute of Traditional Chinese Medicine, School of Chinese Medicine, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan, Taoyuan 333, Taiwan
Interests: hepatology; microbiome; geriatric medicine; sarcopenia; neuromuscular diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

The microbiome consists of microbes that are both helpful and potentially harmful. The gut microbiota contributes extensively to circulating metabolites in the context of liver diseases. The intestinal microbiota may contribute to the high prevalence of metabolic disorders of the human host and, when aberrant, to the pathogenesis of various common metabolic disorders including obesity, cardio-metabolic diseases, type 2 diabetes, non-alcoholic liver disease, inflammatory bowel disease, colorectal cancer, and malnutrition.

This Special Issue aims to highlight examples of microbiota-based therapies to improve metabolic health and outline potential avenues for future epidemiological and experimental studies. All efforts are under way to provide functional insights into the gut microbiota and its mechanisms of action, improve our understanding of the role of the microbiota beyond the gut, and develop microbiota-based strategies so that microbiomes can be applicated in the clinic.

This Special Issue is now open to receive manuscripts on all aspects of gut microbiota, with a particular emphasis on gastroenterology and hepatology.

Dr. Tzung-Yan Lee
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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 microbiota
  • hepatology
  • gastroenterology
  • inflammatory bowel disease
  • colorectal cancer
  • nutrition
  • nature products

Related Special Issue

Published Papers (7 papers)

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Research

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27 pages, 141589 KiB  
Article
Puerarin Modulates Hepatic Farnesoid X Receptor and Gut Microbiota in High-Fat Diet-Induced Obese Mice
by Ching-Wei Yang, Hsuan-Miao Liu, Zi-Yu Chang, Geng-Hao Liu, Hen-Hong Chang, Po-Yu Huang and Tzung-Yan Lee
Int. J. Mol. Sci. 2024, 25(10), 5274; https://doi.org/10.3390/ijms25105274 - 12 May 2024
Viewed by 542
Abstract
Obesity is associated with alterations in lipid metabolism and gut microbiota dysbiosis. This study investigated the effects of puerarin, a bioactive isoflavone, on lipid metabolism disorders and gut microbiota in high-fat diet (HFD)-induced obese mice. Supplementation with puerarin reduced plasma alanine aminotransferase, liver [...] Read more.
Obesity is associated with alterations in lipid metabolism and gut microbiota dysbiosis. This study investigated the effects of puerarin, a bioactive isoflavone, on lipid metabolism disorders and gut microbiota in high-fat diet (HFD)-induced obese mice. Supplementation with puerarin reduced plasma alanine aminotransferase, liver triglyceride, liver free fatty acid (FFA), and improved gut microbiota dysbiosis in obese mice. Puerarin’s beneficial metabolic effects were attenuated when farnesoid X receptor (FXR) was antagonized, suggesting FXR-mediated mechanisms. In hepatocytes, puerarin ameliorated high FFA-induced sterol regulatory element-binding protein (SREBP) 1 signaling, inflammation, and mitochondrial dysfunction in an FXR-dependent manner. In obese mice, puerarin reduced liver damage, regulated hepatic lipogenesis, decreased inflammation, improved mitochondrial function, and modulated mitophagy and ubiquitin-proteasome pathways, but was less effective in FXR knockout mice. Puerarin upregulated hepatic expression of FXR, bile salt export pump (BSEP), and downregulated cytochrome P450 7A1 (CYP7A1) and sodium taurocholate transporter (NTCP), indicating modulation of bile acid synthesis and transport. Puerarin also restored gut microbial diversity, the Firmicutes/Bacteroidetes ratio, and the abundance of Clostridium celatum and Akkermansia muciniphila. This study demonstrates that puerarin effectively ameliorates metabolic disturbances and gut microbiota dysbiosis in obese mice, predominantly through FXR-dependent pathways. These findings underscore puerarin’s potential as a therapeutic agent for managing obesity and enhancing gut health, highlighting its dual role in improving metabolic functions and modulating microbial communities. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology 2.0)
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15 pages, 4636 KiB  
Article
Gut Microbiota in Patients with Non-Alcoholic Fatty Liver Disease without Type 2 Diabetes: Stratified by Body Mass Index
by Natthaya Chuaypen, Aisawan Asumpinawong, Pattarose Sawangsri, Jakkrit Khamjerm, Nutta Iadsee, Thananya Jinato, Sawannee Sutheeworapong, Suthep Udomsawaengsup and Pisit Tangkijvanich
Int. J. Mol. Sci. 2024, 25(3), 1807; https://doi.org/10.3390/ijms25031807 - 2 Feb 2024
Cited by 1 | Viewed by 1302
Abstract
The relationship between gut dysbiosis and body mass index (BMI) in non-diabetic patients with non-alcoholic fatty liver disease (NAFLD) is not adequately characterized. This study aimed to assess gut microbiota’s signature in non-diabetic individuals with NAFLD stratified by BMI. The 16S ribosomal RNA [...] Read more.
The relationship between gut dysbiosis and body mass index (BMI) in non-diabetic patients with non-alcoholic fatty liver disease (NAFLD) is not adequately characterized. This study aimed to assess gut microbiota’s signature in non-diabetic individuals with NAFLD stratified by BMI. The 16S ribosomal RNA sequencing was performed for gut microbiota composition in 100 patients with NAFLD and 16 healthy individuals. The differential abundance of bacterial composition between groups was analyzed using the DESeq2 method. The alpha diversity (Chao1, Shannon, and observed feature) and beta diversity of gut microbiota significantly differed between patients with NAFLD and healthy controls. However, significant differences in their diversities were not observed among subgroups of NAFLD. At the phylum level, there was no trend of an elevated Firmicutes/Bacteroidetes ratio according to BMI. At the genus level, patients with lean NAFLD displayed a significant enrichment of Escherichia-Shigella and the depletion of Lachnospira and Subdoligranulum compared to the non-lean subgroups. Combining these bacterial genera could discriminate lean from non-lean NAFLD with high diagnostic accuracy (AUC of 0.82). Non-diabetic patients with lean NAFLD had a significant difference in bacterial composition compared to non-lean individuals. Our results might provide evidence of gut microbiota signatures associated with the pathophysiology and potential targeting therapy in patients with lean NAFLD. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology 2.0)
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22 pages, 4927 KiB  
Article
Farnesoid X Receptor Agonist GW4064 Protects Lipopolysaccharide-Induced Intestinal Epithelial Barrier Function and Colorectal Tumorigenesis Signaling through the αKlotho/βKlotho/FGFs Pathways in Mice
by Hsuan-Miao Liu, Zi-Yu Chang, Ching-Wei Yang, Hen-Hong Chang and Tzung-Yan Lee
Int. J. Mol. Sci. 2023, 24(23), 16932; https://doi.org/10.3390/ijms242316932 - 29 Nov 2023
Cited by 1 | Viewed by 1231
Abstract
The farnesoid X receptor (FXR)/βKlotho/fibroblast growth factors (FGFs) pathway is crucial for maintaining the intestinal barrier and preventing colorectal cancer (CRC). We used an FXR agonist, GW4064, and FXR-knockout (FXR-KO) mice to investigate the role of FXR/Klothos/FGFs pathways in lipopolysaccharide (LPS)-induced intestinal barrier [...] Read more.
The farnesoid X receptor (FXR)/βKlotho/fibroblast growth factors (FGFs) pathway is crucial for maintaining the intestinal barrier and preventing colorectal cancer (CRC). We used an FXR agonist, GW4064, and FXR-knockout (FXR-KO) mice to investigate the role of FXR/Klothos/FGFs pathways in lipopolysaccharide (LPS)-induced intestinal barrier dysfunction and colon carcinogenesis. The results showed that upregulation of FXR in enterocytes effectively ameliorated intestinal tight-junction markers (claudin1 and zonula occludens-1), inflammation, and bile acid levels, thereby protecting mice from intestinal barrier dysfunction and colon carcinogenesis. GW4064 treatment increased FXR, αKlotho, βKlotho, FGF19, FGF21, and FGF23 in wild-type mice exposed to LPS, while FXR-KO mice had decreased levels. FXR-KO mice exhibited elevated colon cancer markers (β-catenin, LGR5, CD44, CD34, and cyclin D1) under LPS, underscoring the pivotal role of FXR in inhibiting the development of colon tumorigenesis. The varying gut microbiota responses in FXR-KO mice versus wild-type mice post LPS exposure emphasize the pivotal role of FXR in preserving intestinal microbial health, involving Bacteroides thetaiotaomicron, Bacteroides acidifaciens, and Helicobacter hepaticus. Our study validates the effectiveness of GW4064 in alleviating LPS-induced disruptions to the intestinal barrier and colon carcinogenesis, emphasizing the importance of the FXR/αKlotho/βKlotho/FGFs pathway and the interplay between bile acids and gut microbiota. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology 2.0)
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24 pages, 2992 KiB  
Article
Gut Microbiota Patterns in Patients with Non-Alcoholic Fatty Liver Disease: A Comprehensive Assessment Using Three Analysis Methods
by Anna V. Korobeinikova, Olga A. Zlobovskaya, Anna F. Sheptulina, German A. Ashniev, Maria M. Bobrova, Adel A. Yafarova, Dariga U. Akasheva, Shuanat Sh. Kabieva, Siroj Yu. Bakoev, Anjelica V. Zagaynova, Maria V. Lukashina, Ivan A. Abramov, Mariya S. Pokrovskaya, Yurii V. Doludin, Larisa R. Tolkacheva, Alexander S. Kurnosov, Elena V. Zyatenkova, Evgeniya A. Lavrenova, Irina A. Efimova, Evgeniya V. Glazunova, Anton R. Kiselev, German A. Shipulin, Anna V. Kontsevaya, Anton A. Keskinov, Vladimir S. Yudin, Valentin V. Makarov, Oxana M. Drapkina and Sergey M. Yudinadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2023, 24(20), 15272; https://doi.org/10.3390/ijms242015272 - 17 Oct 2023
Cited by 3 | Viewed by 1268
Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease worldwide, affecting nearly 25% of the global adult population. Increasing evidence suggests that functional and compositional changes in the gut microbiota may contribute to the development and promote the progression [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease worldwide, affecting nearly 25% of the global adult population. Increasing evidence suggests that functional and compositional changes in the gut microbiota may contribute to the development and promote the progression of NAFLD. 16S rRNA gene next-generation sequencing is widely used to determine specific features of the NAFLD microbiome, but a complex system such as the gut microbiota requires a comprehensive approach. We used three different approaches: MALDI-TOF-MS of bacterial cultures, qPCR, and 16S NGS sequencing, as well as a wide variety of statistical methods to assess the differences in gut microbiota composition between NAFLD patients without significant fibrosis and the control group. The listed methods showed enrichment in Collinsella sp. and Oscillospiraceae for the control samples and enrichment in Lachnospiraceae (and in particular Dorea sp.) and Veillonellaceae in NAFLD. The families, Bifidobacteriaceae, Lactobacillaceae, and Enterococcaceae (particularly Enterococcus faecium and Enterococcus faecalis), were also found to be important taxa for NAFLD microbiome evaluation. Considering individual method observations, an increase in Candida krusei and a decrease in Bacteroides uniformis for NAFLD patients were detected using MALDI-TOF-MS. An increase in Gracilibacteraceae, Chitinophagaceae, Pirellulaceae, Erysipelatoclostridiaceae, Muribaculaceae, and Comamonadaceae, and a decrease in Acidaminococcaceae in NAFLD were observed with 16S NGS, and enrichment in Fusobacterium nucleatum was shown using qPCR analysis. These findings confirm that NAFLD is associated with changes in gut microbiota composition. Further investigations are required to determine the cause-and-effect relationships and the impact of microbiota-derived compounds on the development and progression of NAFLD. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology 2.0)
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21 pages, 12920 KiB  
Article
Plant Polyphenols Attenuate DSS-induced Ulcerative Colitis in Mice via Antioxidation, Anti-inflammation and Microbiota Regulation
by Huan Chen, Ying Li, Jinrui Wang, Tingting Zheng, Chenyang Wu, Mengyao Cui, Yifan Feng, Hanyi Ye, Zhengqi Dong and Yunjie Dang
Int. J. Mol. Sci. 2023, 24(13), 10828; https://doi.org/10.3390/ijms241310828 - 29 Jun 2023
Cited by 5 | Viewed by 1909
Abstract
The pathogenesis of ulcerative colitis (UC) is associated with inflammation, oxidative stress, and gut microbiota imbalance. Although most researchers have demonstrated the antioxidant bioactivity of the phenolic compounds in plants, their UC-curing ability and underlying mechanisms still need to be further and adequately [...] Read more.
The pathogenesis of ulcerative colitis (UC) is associated with inflammation, oxidative stress, and gut microbiota imbalance. Although most researchers have demonstrated the antioxidant bioactivity of the phenolic compounds in plants, their UC-curing ability and underlying mechanisms still need to be further and adequately explored. Herein, we studied the antioxidation–structure relationship of several common polyphenols in plants including gallic acid, proanthocyanidin, ellagic acid, and tannic acid. Furthermore, the in vivo effects of the plant polyphenols on C57BL/6 mice with dextran-sulfate-sodium-induced UC were evaluated and the action mechanisms were explored. Moreover, the interplay of several mechanisms was determined. The higher the number of phenolic hydroxyl groups, the stronger the antioxidant activity. All polyphenols markedly ameliorated the symptoms and pathological progression of UC in mice. Furthermore, inflammatory cytokine levels were decreased and the intestinal barrier was repaired. The process was regulated by the antioxidant-signaling pathway of nuclear-erythroid 2-related factor 2. Moreover, the diversity of the intestinal microbiota, Firmicutes-to-Bacteroides ratio, and relative abundance of beneficial bacteria were increased. An interplay was observed between microbiota regulation and oxidative stress, immunity, and inflammatory response. Furthermore, intestinal barrier repair was found to be correlated with inflammatory responses. Our study results can form a basis for comprehensively developing plant-polyphenol-related medicinal products. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology 2.0)
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18 pages, 4775 KiB  
Article
Regulation of Gut Microflora by Lactobacillus casei Zhang Attenuates Liver Injury in Mice Caused by Anti-Tuberculosis Drugs
by Yue Li, Liangjie Zhao, Changyu Sun, Jingyi Yang, Xinyue Zhang, Sheng Dou, Qinglian Hua, Aiguo Ma and Jing Cai
Int. J. Mol. Sci. 2023, 24(11), 9444; https://doi.org/10.3390/ijms24119444 - 29 May 2023
Cited by 2 | Viewed by 1719
Abstract
The gut–liver axis may provide a new perspective for treating anti-tuberculosis drug-induced liver injury (ATDILI). Herein, the protective effect of Lactobacillus casei (Lc) was investigated by modulating gut microflora (GM) and the toll like receptor 4 (TLR4)–nuclear factor (NF)-κB–myeloiddifferentiationfactor 88 (MyD88) pathway. C57BL/6J [...] Read more.
The gut–liver axis may provide a new perspective for treating anti-tuberculosis drug-induced liver injury (ATDILI). Herein, the protective effect of Lactobacillus casei (Lc) was investigated by modulating gut microflora (GM) and the toll like receptor 4 (TLR4)–nuclear factor (NF)-κB–myeloiddifferentiationfactor 88 (MyD88) pathway. C57BL/6J mice were given three levels of Lc intragastrically for 2 h before administering isoniazid and rifampicin for 8 weeks. Blood, liver, and colon tissues, as well as cecal contents, were collected for biochemical and histological examination, as well as Western blot, quantitative real time polymerase chain reaction (qRT-PCR), and 16S rRNA analyses. Lc intervention decreased alkaline phosphatase (ALP), superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and tumor necrosis factor (TNF)-α levels (p < 0.05), recovered hepatic lobules, and reduced hepatocyte necrosis to alleviate liver injury induced by anti-tuberculosis drugs. Moreover, Lc also increased the abundance of Lactobacillus and Desulfovibrio and decreased Bilophila abundance, while enhancing zona occludens (ZO)-1 and claudin-1 protein expression compared with the model group (p < 0.05). Furthermore, Lc pretreatment reduced the lipopolysaccharide (LPS) level and downregulated NF-κB and MyD88 protein expression (p < 0.05), thus restraining pathway activation. Spearman correlation analysis indicated that Lactobacillus and Desulfovibrio were positively correlated with ZO-1 or occludin protein expression and negatively correlated with pathway protein expression. Desulfovibrio had significant negative relationships with alanine aminotransferase (ALT) and LPS levels. In contrast, Bilophila had negative associations with ZO-1, occludin, and claudin-1 protein expressions and positive correlations with LPS and pathway proteins. The results prove that Lactobacillus casei can enhance the intestinal barrier and change the composition of the gut microflora. Moreover, Lactobacillus casei may also inhibit TLR4–NF-κB–MyD88 pathway activation and alleviate ATDILI. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology 2.0)
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Review

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20 pages, 2585 KiB  
Review
A Review of the Use of Native and Engineered Probiotics for Colorectal Cancer Therapy
by Huawen Han, Yifan Zhang, Haibo Tang, Tuoyu Zhou and Aman Khan
Int. J. Mol. Sci. 2024, 25(7), 3896; https://doi.org/10.3390/ijms25073896 - 31 Mar 2024
Cited by 1 | Viewed by 1066
Abstract
Colorectal cancer (CRC) is a serious global health concern, and researchers have been investigating different strategies to prevent, treat, or support conventional therapies for CRC. This review article comprehensively covers CRC therapy involving wild-type bacteria, including probiotics and oncolytic bacteria as well as [...] Read more.
Colorectal cancer (CRC) is a serious global health concern, and researchers have been investigating different strategies to prevent, treat, or support conventional therapies for CRC. This review article comprehensively covers CRC therapy involving wild-type bacteria, including probiotics and oncolytic bacteria as well as genetically modified bacteria. Given the close relationship between CRC and the gut microbiota, it is crucial to compile and present a comprehensive overview of bacterial therapies used in the context of colorectal cancer. It is evident that the use of native and engineered probiotics for colorectal cancer therapy necessitates research focused on enhancing the therapeutic properties of probiotic strains.. Genetically engineered probiotics might be designed to produce particular molecules or to target cancer cells more effectively and cure CRC patients. Full article
(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology 2.0)
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