scholarly journals Obeticholic Acid Inhibits Anxiety via Alleviating Gut Microbiota-Mediated Microglia Accumulation in the Brain of High-Fat High-Sugar Diet Mice

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 940
Author(s):  
Li Wu ◽  
Yuqiu Han ◽  
Zhipeng Zheng ◽  
Shuai Zhu ◽  
Jun Chen ◽  
...  
Keyword(s):  
Metabolic Disorders ◽  
Intestinal Barrier ◽  
Behavioral Performance ◽  
High Fat ◽  
Barrier Dysfunction ◽  
Obeticholic Acid ◽  
Promising Agent ◽  
Serum Biochemical ◽  
Lipid Metabolites ◽  
The Brain

Anxiety is one of the complications of metabolic disorders (MDs). Obeticholic acid (OCA), the bile acids (BAs) derivative, is a promising agent for improving MDs in association with gut dysbiosis. Yet, its protective effect on MDs-driven anxiety remains unknown. Here, we assessed the serum biochemical parameters and behavioral performance by open field and Morris water maze tests in HFHS diet-induced MDs mice after OCA intervention for nine and 18 weeks. Moreover, antibiotics intervention for microbial depletion was conducted simultaneously. We found that OCA treatment inhibited the initiation and progression of anxiety in HFHS diet-MDs mice via a microbiota–BAs–brain axis: OCA decreased the neuroinflammatory microglia and IL-1β expression in the hippocampus, reversed intestinal barrier dysfunction and serum proinflammatory LPS to a normal level, modified the microbial community, including the known anxiety-related Rikenellaceae and Alistipes, and improved the microbial metabolites especially the increased BAs in feces and circulation. Moreover, the OCA-reversed bile acid taurocholate linked disordered serum lipid metabolites and indole derivatives to anxiety as assessed by network analysis. Additionally, microbial depletion with antibiotics also improved the anxiety, microgliosis and BAs enrichment in the experimental MDs mice. Together, these findings provide microbiota–BAs–brain axis as a novel therapeutic target for MDs-associated neuropsychiatric disorders.

The ameliorative effect of the Pyracantha fortuneana (Maxim.) H. L. Li extract on intestinal barrier dysfunction through modulating glycolipid digestion and gut microbiota in high fat diet-fed rats

2019 ◽  
Vol 10 (10) ◽  
pp. 6517-6532 ◽  
Author(s):  
Hang Xu ◽  
Chunfang Zhao ◽  
Yutian Li ◽  
Ruiyu Liu ◽  
Mingzhang Ao ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
Intestinal Barrier ◽  
High Fat ◽  
Barrier Dysfunction ◽  
Fruit Extract ◽  
Intestinal Barrier Dysfunction ◽  
Beneficial Effects ◽  
Obese Rats ◽  
Ameliorative Effect

Pyracantha fortuneana fruit extract (PFE) exhibits beneficial effects on IBF in association with the modulation of glycolipid digestion and gut microbiota in HFD-fed obese rats.

scholarly journals Modulation of the Gut Microbiota by Shen-Yan-Fang-Shuai Formula Improves Obesity Induced by High-Fat Diets

2020 ◽  
Vol 11 ◽  
Author(s):  
Zhen Wang ◽  
Junfeng Lu ◽  
Jingwei Zhou ◽  
Weiwei Sun ◽  
Yang Qiu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Metabolic Disorders ◽  
Intestinal Barrier ◽  
Fecal Microbiota ◽  
16S Rrna Genes ◽  
Rrna Genes ◽  
Therapeutic Effects ◽  
Low Grade ◽  
High Fat ◽  
Gut Barrier Function

Obesity and related metabolic disorders are associated with intestinal microbiota dysbiosis, disrupted intestinal barrier and chronic inflammation. Shen-Yan-Fang-Shuai formula (SYFSF) is a traditional Chinese herbal formula composed of Astragali Radix, Radix Angelicae Sinensis, Rheum Officinale Baill, and four other herbs. In this study, we identified that SYFSF treatment prevented weight gain, low-grade inflammation and insulin resistance in high-fat diet (HFD)-fed mice. SYFSF also substantially improved gut barrier function, reduced metabolic endotoxemia, as well as systemic inflammation. Sequencing of 16S rRNA genes obtained from fecal samples demonstrated that SYFSF attenuated HFD-induced gut dysbiosis, seen an decreased Firmicutes to Bacteroidetes ratios. Microbial richness and diversity were also higher in the SYFSF-treated HFD group. Furthermore, similar therapeutic effects and changes in gut microbiota profile caused by SYFSF could be replicated by fecal microbiota transfer (FMT). Taken together, our study highlights the efficacy of SYFSF in preventing obesity and related metabolic disorders. Its therapeutic effect is associated with the modulation of gut microbiota, as a prebiotic.

Polysaccharide from Rosa roxburghii Tratt fruit attenuates high-fat diet-induced intestinal barrier dysfunction and inflammation in mice by modulating gut microbiota

2022 ◽  
Author(s):  
Lei Wang ◽  
Pan Zhang ◽  
Chao Li ◽  
Fei Xu ◽  
Jie Chen
Keyword(s):  
Colorectal Cancer ◽  
High Fat Diet ◽  
Inflammatory Diseases ◽  
Intestinal Barrier ◽  
High Fat ◽  
Barrier Dysfunction ◽  
Effective Agent ◽  
Colonic Inflammation ◽  
Rosa Roxburghii Tratt ◽  
Rosa Roxburghii

Obesity-induced colonic inflammation-stimulated colitis is one of the main causes of colorectal cancer. Dietary polysaccharides are considered an effective agent for relieving obesity-induced inflammatory diseases such as diabetes and colitis....

Abstract TP336: The Intestinal Barrier Dysfunction Induced by Intracerebral Hemorrhage Contributes to the Brain Edema

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Tian Wang ◽  
Bing Han ◽  
Yingjie Han ◽  
Ting Li ◽  
Fenghua Fu
Keyword(s):  
Intracerebral Hemorrhage ◽  
Brain Edema ◽  
Intestinal Permeability ◽  
Sham Group ◽  
Intestinal Barrier ◽  
Intestinal Injury ◽  
Brain Water Content ◽  
Barrier Dysfunction ◽  
The Brain ◽  
Brain Water

Background and Purpose: This study aims to investigate whether intracerebral hemorrhage (ICH) can lead to intestinal barrier dysfunction, and whether ICH-induced intestinal injury plays a role in brain edema. Methods: ICH mice model was prepared by an intrastriatal injection of bacterial collagenase. The following parameters were investigated at 3 h, 6 h, 12 h, 1 d, 2 d, 3 d, or 7 d after ICH preparation. Mice were given intragastrically with FITC-dextran and the intestinal permeability was evaluated by serum fluorescence measurement. Serum lipopolysaccharide (LPS) level was assayed with ELISA kits. Ileum and jejunum were stained with hematoxylin and eosin. Intestinal mucosal injuries were graded according to the scoring method (grade 0 to grade 4). Brain water content was evaluated via a wet/dry weight method. Correlations of intestinal injury, intestine permeability, LPS, and brain edema were analyzed using Pearson’s correlation analysis. Results: Compared with the Sham group, Ileum and jejunum damage occurred at 6 h after ICH, and the ICH-induced intestinal injury continued until 7 d. In line with the histopathological findings, the degree of ileum and jejunum injury was significantly increased at 6 h after ICH, showing mostly scores in Grade 1 to Grade 3 ( P < 0.05 or P < 0.01). After 6-h ICH, the intestinal permeability to FITC-dextran was higher compared to the Sham group, and the increase of intestinal permeability lasted 7 d ( P < 0.01). From 6 h to 7 d, serum LPS was significantly augmented ( P < 0.01). The brain content of the ipsilateral hemispheres was increased at 12 h, 1 d, 2 d, and 3 d after ICH ( P < 0.05 or P < 0.01), and the brain content of the contralateral hemispheres was also enhanced at 1 d, 2 d, and 3 d after ICH ( P < 0.01). The ileum and jejunum injury were positively associated with intestine permeability (r = 0.625, P < 0.01, r = 0.465, P < 0.01, respectively). The intestine permeability was positively associated with the serum level of LPS (r =0.585, P < 0.01). The LPS levels were positively associated with brain water content (r = 0.338, P < 0.01). Conclusion: ICH can cause intestinal mucosal injury. Consequently, the increase of intestinal permeability results in the translocation of endotoxins, which contributes to ICH-induced brain edema.

scholarly journals Off the Clock: From Circadian Disruption to Metabolic Disease

2019 ◽  
Vol 20 (7) ◽  
pp. 1597 ◽  
Author(s):  
Eleonore Maury
Keyword(s):  
Metabolic Disease ◽  
Metabolic Disorders ◽  
Jet Lag ◽  
High Fat ◽  
Peripheral Tissues ◽  
Temporal Regulation ◽  
The Impact ◽  
Fat Feeding ◽  
The Brain ◽  
Daily Changes

Circadian timekeeping allows appropriate temporal regulation of an organism’s internal metabolism to anticipate and respond to recurrent daily changes in the environment. Evidence from animal genetic models and from humans under circadian misalignment (such as shift work or jet lag) shows that disruption of circadian rhythms contributes to the development of obesity and metabolic disease. Inappropriate timing of food intake and high-fat feeding also lead to disruptions of the temporal coordination of metabolism and physiology and subsequently promote its pathogenesis. This review illustrates the impact of genetically or environmentally induced molecular clock disruption (at the level of the brain and peripheral tissues) and the interplay between the circadian system and metabolic processes. Here, we discuss some mechanisms responsible for diet-induced circadian desynchrony and consider the impact of nutritional cues in inter-organ communication, with a particular focus on the communication between peripheral organs and brain. Finally, we discuss the relay of environmental information by signal-dependent transcription factors to adjust the timing of gene oscillations. Collectively, a better knowledge of the mechanisms by which the circadian clock function can be compromised will lead to novel preventive and therapeutic strategies for obesity and other metabolic disorders arising from circadian desynchrony.

scholarly journals Death following traumatic brain injury in Drosophila is associated with intestinal barrier dysfunction

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Rebeccah J Katzenberger ◽  
Stanislava Chtarbanova ◽  
Stacey A Rimkus ◽  
Julie A Fischer ◽  
Gulpreet Kaur ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Genome Wide Association Study ◽  
Intestinal Barrier ◽  
Nucleotide Polymorphisms ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Probability Of Death ◽  
Highly Correlated ◽  
The Brain

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Unfavorable TBI outcomes result from primary mechanical injuries to the brain and ensuing secondary non-mechanical injuries that are not limited to the brain. Our genome-wide association study of Drosophila melanogaster revealed that the probability of death following TBI is associated with single nucleotide polymorphisms in genes involved in tissue barrier function and glucose homeostasis. We found that TBI causes intestinal and blood–brain barrier dysfunction and that intestinal barrier dysfunction is highly correlated with the probability of death. Furthermore, we found that ingestion of glucose after a primary injury increases the probability of death through a secondary injury mechanism that exacerbates intestinal barrier dysfunction. Our results indicate that natural variation in the probability of death following TBI is due in part to genetic differences that affect intestinal barrier dysfunction.

scholarly journals EXPERIMENTAL INTESTINAL DYSBIOSIS IN RATS INCREASES THE PERMEABILITY OF THE BLOOD-BRAIN BARRIER AND INDUCES NEUROINFLAMMATION

2019 ◽  
Vol 19 (1S) ◽  
pp. 104-105
Author(s):  
V G Sergeyev ◽  
T N Sergeyeva
Keyword(s):  
Blood Brain Barrier ◽  
Intestinal Barrier ◽  
Alpha Synuclein ◽  
Brain Barrier ◽  
Local Inflammation ◽  
Barrier Dysfunction ◽  
Cellular Mechanisms ◽  
Blood Brain ◽  
Intestinal Dysbiosis ◽  
The Brain

The mammalian intestinal microbiota consists of bacteria, fungi and viruses, including bacteriophages. This complex ecosystem has dynamic stability. It is assumed that changes in the composition of the microbiota can cause intestinal barrier dysfunction and the development of a number of pathologies, including neurodegenerative diseases accompanied by neuroinflammation. The molecular and cellular mechanisms underlying such a relationship remain poorly understood. We hypothesized that bacteriophages cause intestinal dysbiosis, increased intestinal permeability and local inflammation. Bacterial factors (endotoxins, zonulin-like proteins) and local inflammation products (cytokines, alpha-synuclein protein) can enter the circulation and increase the permeability of the blood-brain barrier (BBB), which will cause neuro-inflammation and damage to neurons. In this study, we observed an increase in BBB permeability and induction of neuroinflammation in the brain after rectal administration of a bacteriophage cocktail (Microgen, Russia). The permeability of the BBB was judged by the volume of the vital dye (Evans blue) emerging from the bloodstream into the brain parenchyma, and the development of the neuroinflammatory response by increasing the number of immunohistochemically stained microglial and astroglial cells.

scholarly journals Intestinal Barrier Dysfunction Exacerbates Neuroinflammation via the TLR4 Pathway in Mice With Heart Failure

2021 ◽  
Vol 12 ◽  
Author(s):  
Jun-Yu Huo ◽  
Wan-Ying Jiang ◽  
Ting Yin ◽  
Hai Xu ◽  
Yi-Ting Lyu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Intestinal Permeability ◽  
Intestinal Barrier ◽  
Sham Operation ◽  
Barrier Dysfunction ◽  
Intestinal Alkaline Phosphatase ◽  
Intestinal Barrier Dysfunction ◽  
Junction Protein ◽  
Elevated Expression ◽  
The Brain

AimsThe present study aimed to investigate alterations in neuroinflammation after heart failure (HF) and explore the potential mechanisms.MethodsMale wild-type (WT) and Toll-like receptor 4 (TLR4)-knockout (KO) mice were subjected to sham operation or ligation of the left anterior descending coronary artery to induce HF. 8 weeks later, cardiac functions were analyzed by echocardiography, and intestinal barrier functions were examined by measuring tight junction protein expression, intestinal permeability and plasma metabolite levels. Alterations in neuroinflammation in the brain were examined by measuring microglial activation, inflammatory cytokine levels and the proinflammatory signaling pathway. The intestinal barrier protector intestinal alkaline phosphatase (IAP) and intestinal homeostasis inhibitor L-phenylalanine (L-Phe) were used to examine the relationship between intestinal barrier dysfunction and neuroinflammation in mice with HF.ResultsEight weeks later, WT mice with HF displayed obvious increases in intestinal permeability and plasma lipopolysaccharide (LPS) levels, which were accompanied by elevated expression of TLR4 in the brain and enhanced neuroinflammation. Treatment with the intestinal barrier protector IAP significantly attenuated neuroinflammation after HF while effectively increasing plasma LPS levels. TLR4-KO mice showed significant improvements in HF-induced neuroinflammation, which was not markedly affected by intestinal barrier inhibitors or protectors.ConclusionHF could induce intestinal barrier dysfunction and increase gut-to-blood translocation of LPS, which could further promote neuroinflammation through the TLR4 pathway.

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