Interleukin-17 Weakens the NAFLD/NASH Process by Facilitating Intestinal Barrier Restoration Depending on the Gut Microbiota

He, Shuang-Hui; Cui, Shudan; Song, W. Y.; Jiang, Yu; Chen, Hongsheng; Liao, Dongjiang; Lu, Xinpeng; Li, Jun; Chen, Xueqing; Peng, Liang

doi:10.1128/mbio.03688-21

Cited by 26 publications

(18 citation statements)

References 45 publications

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“…The deletion of Akt1 and Akt2 in the liver has been shown to cause liver inflammation and hepatocyte death, and the use of PI3K/AKT inhibitors has been shown to significantly enhance the degree of liver damage in mice ( Reyes-Gordillo et al, 2019 ). Furthermore, the IL-17 and VEGF signaling pathways may contribute to a decrease in HF ( Kumar et al, 2016 ; Fabre et al, 2018 ; Martínez-López et al, 2019 ; Qiao et al, 2020 ; Ghanim et al, 2021 ; He et al, 2022 ). Huiji Pan et al discovered that gut microbiota influence H-L + HFD-induced liver fibrosis through alteration of the hepatic IRS1/Akt/mTOR signaling pathway ( Pan et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Exploration of the potential mechanism of Baicalin for hepatic fibrosis based on network pharmacology, gut microbiota, and experimental validation

et al. 2023

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Baicalin (BA) is among the most effective and abundant flavonoids extracted from Scutellaria baicalensis that may be utilized to treat diseases associated with hepatic fibrosis (HF). Through network pharmacology, gut microbiota, and experimental validation, this research intends to elucidate the multi-target mechanism of BA on HF. BA targets were screened using databases and literature. As a result, In the anti-HF mechanism, the BA and 191 HF-associated targets interact, with 9 specific targets indicating that the BA’s anti-HF mechanism is closely linked to gut microbiota. Consequently, rat intestinal content samples were obtained and examined using 16S rRNA sequencing. In the BA-treated group, the gut microbiota was positively regulated at the phylum,and genus levels, with Lactobacillus performing significantly. The study concluded that BA has a multi-targeted anti-HF effect and has changed the gut microbial ecosystem.

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Section: Discussionmentioning

confidence: 99%

Exploration of the potential mechanism of Baicalin for hepatic fibrosis based on network pharmacology, gut microbiota, and experimental validation

et al. 2023

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“…(2) Estrogen signaling pathway: The lack of estrogen accelerates hepatic steatosis progression, in particular, which is exposed noticeably to post-menopausal women with metabolic disorders 28 . (3) Interleukin-17 (IL-17) signaling pathway: A report demonstrated that IL-17 could enhance intestinal epithelial layer and diminish dysbacteriosis-caused intestinal damage and other organs injury incited by a diet 29 . Noticeably, Relaxin signaling pathway, Estrogen signaling pathway, and IL-17 signaling pathway are related directly to JUN in the treatment of NAFLD, indicating that the three signaling pathways might exert its therapeutic value on NAFLD.…”

Section: Discussionmentioning

confidence: 99%

The combined application of Hordeum vulgare and gut microbiota against non-alcoholic fatty liver disease via network pharmacology approach

Lee

Gupta

Min

et al. 2022

Preprint

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Non-alcoholic fatty liver disease (NAFLD) is an initial etiology to be developed steatosis, liver fibrosis, cirrhosis, and even hepatocellular carcinoma. However, the noticeable therapeutics were not elucidated completely to dampen the progressive rate involved in NAFLD. In the incomplete project, we combined secondary metabolites (SMs) from gut microbiota (GM) and Hordeum vulgare (HV) as a representative grain with potent NAFLD to exert combinatorial effects via network pharmacology. Hence, we retrieved the SMs of HV from NPASS (Natural product Activity & Species Source Database) and SMs of GM from gutMGene database. Then, targets associated with SMs were identified from both SEA (Similarity Ensemble Approach) and STP (SwissTargetPrediction). The crucial overlapping targets were identified on NAFLD-related targets through Ven diagram plotter. We constructed the protein-protein interaction (PPI) network from the crucial targets and built a bubble plot to identify a key mechanism on NAFLD. Also, we analyzed microbiota or barley – signaling pathways – targets – metabolites (MBSTM) in aspects of combinatorial approach (HV, and GM). To be confirmed a significant SM against NAFLD, we performed Molecular Docking (MD) with Autodock 1.5.6 to verify the affinity between SMs and targets. Finally, drug-likeness and toxicity properties of key SMs were validated via SwissADME and ADMETlab platform. The number of 31 core targets was analyzed by PPI network, the result of which represented JUN as a key target on NAFLD. The key SM bound stably to JUN were Tryptanthrin from HV. On a bubble plot, we identified that Apelin signaling pathway might be an inhibitive mechanism to relieve NAFLD in the combinatorial approach. On the holistic viewpoints, we analyzed MBSTM to obtain components associated with Apelin signaling pathway. As a result, we found the primary GM to fight NAFLD: Microbiota (Eubacterium limosum; Eggerthella sp. SDG-2; Alistipes indistinctus YIT 12060; Odoribacter laneus YIT 12061; Paraprevotella clara YIT 11840; Paraprevotella xylaniphila YIT 11841). The MD provided what the key SM (Dihydroglycitein, 1,3-Diphenylpropan-2-ol, and Acetic) is on each target (HDAC5, NOS1, and NOS2) related directly to Apelin signaling pathway. Overall, these results suggest that combinatorial application could be an effective tactic for ameliorating NAFLD.

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“…114 Furthermore, a recent study comparing IL-17 À/À mice fed an MCD diet and IL17 +/+ mice fed an MCD diet found that IL-17 is crucial for regulating the balance of gut microbiota and intestinal barrier integrity. 115 In addition, the study suggested that the protective effect of IL-17 in maintaining intestinal barrier integrity may outweigh its potential for tissue damage in NAFLD/NASH. However, further research is needed to fully understand the specific mechanisms involved.…”

Section: Changes In Microbesmentioning

confidence: 99%

Composition of gut microbiota and non‐alcoholic fatty liver disease: A systematic review and meta‐analysis

Su,

Chen,

Liu

et al. 2023

Obesity Reviews

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SummaryThe present systematic review and meta‐analysis aimed to summarize the associations between gut microbiota composition and non‐alcoholic fatty liver disease. To compare the differences between individuals with or without NAFLD, the standardized mean difference and 95% confidence interval were computed for each α‐diversity index and relative abundance of gut microbes. The β‐diversity indices were summarized in a qualitative manner. A total of 54 studies with 8894 participants were included. Overall, patients with NAFLD had moderate reduction in α‐diversity indices including Shannon (SMD = −0.36, 95% CI = [−0.53, −0.19], p < 0.001) and Chao 1 (SMD = −0.42, 95% CI = [−0.68, −0.17], p = 0.001), but no significant differences were found for Simpson, observed species, phylogenetic diversity, richness, abundance‐based coverage estimator, and evenness (p ranged from 0.081 to 0.953). Over 75% of the included studies reported significant differences in β‐diversity. Although there was substantial interstudy heterogeneity, especially for analyses at the phylum, class, and family levels, the majority of the included studies showed alterations in the depletion of anti‐inflammatory microbes (i.e., Ruminococcaceae and Coprococcus) and the enrichment of proinflammatory microbes (i.e., Fusobacterium and Escherichia) in patients with NAFLD. Perturbations in gut microbiota were associated with NAFLD, commonly reflected by a reduction in beneficial species and an increase in the pathogenic species.

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Interleukin-17 Weakens the NAFLD/NASH Process by Facilitating Intestinal Barrier Restoration Depending on the Gut Microbiota

Cited by 26 publications

References 45 publications

Exploration of the potential mechanism of Baicalin for hepatic fibrosis based on network pharmacology, gut microbiota, and experimental validation

Exploration of the potential mechanism of Baicalin for hepatic fibrosis based on network pharmacology, gut microbiota, and experimental validation

The combined application of Hordeum vulgare and gut microbiota against non-alcoholic fatty liver disease via network pharmacology approach

Composition of gut microbiota and non‐alcoholic fatty liver disease: A systematic review and meta‐analysis

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