Ferulic acid improves intestinal barrier function through altering gut microbiota composition in high-fat diet-induced mice

Tian, Baoming; Geng, Yan; Wang, Peiyi; Cai, Ming; Neng, Jing; Hu, Jiang‐Ning; Xia, Daozong; Cao, Wangli; Yang, Kai; Sun, Peilong

doi:10.1007/s00394-022-02927-7

Cited by 62 publications

(31 citation statements)

References 56 publications

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“…Furthermore, our data demonstrated that FA is negatively correlated with 9 bacteria species, all of which were positively correlated with the host phenotypes, such as body weight, BMI, TC,T, LH, FBG, INS and HOMA-IR. Consistently, previous studies shown that FA improves a variety of disorders through modulating gut microbiota ( 31 , 32 , 63 , 64 ). Our untargeted metabolomics predicted the roles of some metabolites, and we showed that ferulic acid and the other metabolites (such as folic acid, stachyose, etc.)…”

Section: Discussionsupporting

confidence: 88%

Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome

Wang

Yang

et al. 2023

Front. Endocrinol.

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BackgroundPolycystic ovarian syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism, ovarian dysfunction and polycystic ovarian morphology. Gut microbiota dysbiosis and metabolite are associated with PCOS clinical parameters. Yulin Tong Bu formula (YLTB), a traditional Chinese medicine formula, has been recently indicated to be capable of ameliorating polycystic ovary symptoms and correcting abnormal glucose metabolism. However, the therapeutic mechanism of YLTB on PCOS has not been fully elucidated.MethodsA pseudo sterile mouse model was established during this four-day acclimatization phase by giving the animals an antibiotic cocktail to remove the gut microbiota. Here, the therapeutic effects of YLTB on PCOS were investigated using dehydroepiandrosterone plus high-fat diet-induced PCOS mice model. Female prepuberal mice were randomly divided into three groups; namely, the control group, PCOS group and YLTB (38.68 g·kg-1·day-1) group. To test whether this effect is associated with the gut microbiota, we performed 16S rRNA sequencing studies to analyze the fecal microbiota of mice. The relationships among metabolites, gut microbiota, and PCOS phenotypes were further explored by using Spearman correlation analysis. Then, the effect of metabolite ferulic acid was then validated in PCOS mice.ResultsOur results showed that YLTB treatment ameliorated PCOS features (ovarian dysfunction, delayed glucose clearance, decreased insulin sensitivity, deregulation of glucolipid metabolism and hormones, etc.) and significantly attenuated PCOS gut microbiota dysbiosis. Spearman correlation analysis showed that metabolites such as ferulic acid and folic acid are negatively correlated with PCOS clinical parameters. The effect of ferulic acid was similar to that of YLTB. In addition, the bacterial species such as Bacteroides dorei and Bacteroides fragilis were found to be positively related to PCOS clinical parameters, using the association study analysis.ConclusionThese results suggest that YLTB treatment systematically regulates the interaction between the gut microbiota and the associated metabolites to ameliorate PCOS, providing a solid theoretical basis for further validation of YLTB effect on human PCOS trials.

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Section: Discussionsupporting

confidence: 88%

Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome

Wang

Yang

et al. 2023

Front. Endocrinol.

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“…Fig.1D ). In particular, SCFA producing taxa, including Faecalibaculum and Agathobaculum [38], were arrhythmic in Bmal1 SCNfl/- mice ( Fig. 2F, G, Suppl.…”

Section: Resultsmentioning

confidence: 99%

Genetic and environmental circadian disruption induce metabolic impairment through changes in the gut microbiome

Altaha

Heddes

Pilorz

et al. 2022

Preprint

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Objective: Internal clocks time behavior and physiology, including the gut microbiome in a circadian (~24 h) manner. Mismatch between internal and external time, e.g. during shift work, disrupts circadian system coordination promoting the development of obesity and type 2 diabetes (T2D). Conversely, body weight changes induce microbiota dysbiosis. The relationship between circadian disruption and microbiota dysbiosis in metabolic diseases, however, remains largely unknown. Methods: Core and accessory clock gene expression in different gastrointestinal (GI) tissues were determined by qPCR in two different models of circadian disruption - mice with Bmal1 deficiency in the circadian pacemaker, the suprachiasmatic nucleus (Bmal1SCNfl/-), and wild-type mice exposed to simulated shift work (SSW). Body composition and energy balance were evaluated by nuclear magnetic resonance (NMR), bomb calorimetry, food intake and running-wheel activity. Intestinal permeability was measured in an Ussing chamber. Microbiota composition and functionality were evaluated by 16S rRNA gene amplicon sequencing, PICRUST2.0 analysis and targeted metabolomics. Finally, microbiota transfer was conducted to evaluate the functional impact of SSW-associated microbiota on the hosts physiology. Results: Both chronodisruption models show desynchronization within and between peripheral clocks in GI tissues and reduced microbial rhythmicity, in particular in taxa involved in short-chain fatty acid (SCFA) fermentation and lipid metabolism. In Bmal1SCNfl/- mice, loss of rhythmicity in microbial functioning associates with previously shown increased body weight, dysfunctional glucose homeostasis and adiposity. Similarly, we observe an increase in body weight in SSW mice. Germ-free colonization experiments with SSW-associated microbiota mechanistically link body weight gain to microbial changes. Moreover, alterations in expression of peripheral clock genes as well as clock-controlled genes (CCGs) relevant for metabolic functioning of the host were observed in recipients, indicating a bidirectional relationship between microbiota rhythmicity and peripheral clock regulation. Conclusions: Collectively, our data suggest that loss of rhythmicity in bacteria taxa and their products, which likely originates in desynchronization of intestinal clocks, promotes metabolic abnormalities during shift work.

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“…In a human study, FA intake was shown to enhance the number of Bacteroidetes and decrease the population of Firmicutes in the microbiome analysis [ 72 ]. In vivo studies have also shown that FA can mitigate intestinal inflammation, promote the growth of Bacteroides, and induce the production of SCFAs by modulating the gut microbiota in mouse and diabetic syndrome rat model [ 73 , 74 ]. Feruloyl Oligosaccharides (FOs), the ferulic acid ester of oligosaccharides, has been reported to strengthen the antioxidative capacity of the jejunum and alter the structure and composition of the cecal microbiota in rats by increasing the relative abundances of Actinobacteria, Proteobacteria while decreasing the abundance of Firmicutes.…”

Section: Discussionmentioning

confidence: 99%

Ferulic Acid as a Protective Antioxidant of Human Intestinal Epithelial Cells

et al. 2022

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The intestinal epithelial barrier is the primary and most significant defense barrier against ingested toxins and pathogenic bacteria. When the intestinal epithelium barrier is breached, inflammatory response is triggered. GWAS data showed that endoplasmic reticulum (ER) stress markers are elevated in Inflammatory Bowel Disease (IBD) patients, which suggests ER stress regulation might alleviate IBD symptoms. Ferulic acid (FA) is a polyphenol that is abundant in plants and has antioxidant and anti-inflammatory properties, although it is unclear whether FA has these effects on the intestine. Therefore, we investigated the effect of FA in vitro and in vivo. It was found that FA suppressed ER stress, nitric oxide (NO) generation, and inflammation in polarized Caco-2 and T84 cells, indicating that the ER stress pathway was implicated in its anti-inflammatory activities. The permeability of polarized Caco-2 cells in the presence and absence of proinflammatory cytokines were decreased by FA, and MUC2 mRNA was overexpressed in the intestines of mice fed a high-fat diet (HFD) supplemented with FA. These results suggest that FA has a protective effect on intestinal tight junctions. In addition, mouse intestine organoids proliferated significantly more in the presence of FA. Our findings shed light on the molecular mechanism responsible for the antioxidant effects of FA and its protective benefits on the health of the digestive system.

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Ferulic acid improves intestinal barrier function through altering gut microbiota composition in high-fat diet-induced mice

Cited by 62 publications

References 56 publications

Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome

Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome

Genetic and environmental circadian disruption induce metabolic impairment through changes in the gut microbiome

Ferulic Acid as a Protective Antioxidant of Human Intestinal Epithelial Cells

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