β-Sitosterol Ameliorates Endometrium Receptivity in PCOS-Like Mice: The Mediation of Gut Microbiota

Background: Polycystic ovary syndrome (PCOS), one of the most common endocrine diseases in women of childbearing age, has been found to be accompanied by changes in the gut microbiota. The Bu Shen Yang Xue formula (BSYXF) is a traditional Chinese medicine widely used for the treatment of PCOS. This study aimed to investigate whether the protective effects of β-sitosterol, the main active ingredient of BSYXF, on PCOS was mediated by regulating gut microbiota.Methods: The presence of β-sitosterol in BSYXF was detected by liquid chromatography-mass spectrometry. The PCOS-like mouse model was induced by dehydroepiandrosterone. The fecal supernatant of β-sitosterol-treated mice was prepared for fecal microbiota transplantation (FMT). Body weight and wet weight of the uterus and ovary of the mice were recorded for organ index calculation. Hematoxylin and eosin stain was used to assess the endometrial morphology and microenvironment changes. Expression of endometrial receptivity markers cyclooxygenase-2 (COX-2), Integrin ανβ3, leukemia inhibitory factor (LIF), and homeobox A10 (HOXA10) in the endometrium were determined by immunohistochemistry and western blot analysis. Enzyme-linked immunosorbent assay was employed to detect the expression of follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), and testosterone (T) in the serum. The diversity of gut microbiota was examined by 16S rDNA gene sequencing.Results: With the treatment of β-sitosterol and β-sitosterol-FMT, the uterine index of PCOS-like mice increased, the ovarian index decreased, levels of COX-2, LH and T decreased, and levels of Integrin ανβ3, LIF, HOXA10, FSH, and P increased. Under β-sitosterol treatment, the structure of the gut microbiota in PCOS-like mice was also changed.Conclusion: β-sitosterol regulates the endometrial receptivity of PCOS and harmonizes the sex hormone balance, which may be related to the changes in the structure and composition of gut microbiota, thus affecting the pathological process of PCOS.

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The effect of Sennoside A on the improvement of lipopolysaccharide -associated encephalopathy through gut microbiota

10.21203/rs.3.rs-201567/v1 ◽

2021 ◽

Author(s):

Suyan Li ◽

Fenyan Zhang ◽

Yiguang Lin ◽

Xiaoli Niu ◽

Jian Lv ◽

...

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Intestinal Flora ◽

Fecal Microbiota ◽

Protective Effects ◽

Sprague Dawley ◽

Microbial Composition ◽

Germ Free ◽

Sd Rats ◽

Tnf Α

Abstract Background Accumulating evidence suggests that the intestinal flora is involved in many neurodegenerative diseases. Sepsis can lead to severe intestinal flora imbalance and brain dysfunction. In this study, we investigated Sennoside A may relieve lipopolysaccharide(LPS)-associated encephalopathy via its effect on the gut microbiota in rats. Methods Adult male Sprague-Dawley (SD) rats and germ free (GF) rats were used. The ordinary and germ free SD rats were adopted as a LPS-associated encephalopathy model with or without Sennoside A administration. We investigated gut microbiota diversity and structure, conducted electroencephalograms (EEG) and measured the levels of TNF-α, IL-1β and IL-6 in the cortexes of Sprague Dawley (SD) rats with or without Sennoside A administration. Horizontal fecal microbiota transplantation (FMT) and germ-free rats were used to confirm the important roles of gut microbiota in the mitigation of LPS-associated encephalopathy in rats after Sennoside A supplementation. Results We found that Sennoside A treatment markedly improved brain function in septic rats including decreased ratios of abnormal EEG and lowered levels of TNF-α, IL-1β, and IL-6 in the rat cortexes. While the gut microbiota changed in septic SD rats, Sennoside A improved gut microbial composition, which might mediate its brain protective effects in sepsis. Sennoside A also reduced inflammation in the cortexes of septic rats via gut microbiota improvement. In germ-free rats that received lipopolysaccharide(LPS),Sennoside A could not lower the ratios of abnormal EEG, and could not alleviate TNF-α, IL-1β, and IL-6 levels in the rats’ cortexes. FMT lowered the ratios of abnormal EEG and alleviate TNF-α, IL-1β, and IL-6 levels in rats’ cortexes, which confirmed our hypothesis that the effect of Sennoside A on the improvement of LPS-associated encephalopathy through gut microbiota. Conclusion Our data confirm our hypothesis that Sennoside A likely exerts its brain protective effects through gut microbiota alteration.

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Gut Microbiota-Derived l-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury

International Journal of Molecular Sciences ◽

10.3390/ijms222111436 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11436

Author(s):

Zhiyuan Chen ◽

Bin Wang ◽

Jiali Dong ◽

Yuan Li ◽

Shuqin Zhang ◽

...

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Systolic Function ◽

Circulatory System ◽

Fecal Microbiota ◽

Oral Route ◽

Pathological Process ◽

Dependent Manner ◽

Radiation Induced ◽

Chest Irradiation

Radiation-induced cardiopulmonary injuries are the most common and intractable side effects that are entwined with radiotherapy for thorax cancers. However, the therapeutic options for such complications have yielded disappointing results in clinical applications. Here, we reported that gut microbiota-derived l-Histidine and its secondary metabolite imidazole propionate (ImP) fought against radiation-induced cardiopulmonary injury in an entiric flora-dependent manner in mouse models. Local chest irradiation decreased the level of l-Histidine in fecal pellets, which was increased following fecal microbiota transplantation. l-Histidine replenishment via an oral route retarded the pathological process of lung and heart tissues and improved lung respiratory and heart systolic function following radiation exposure. l-Histidine preserved the gut bacterial taxonomic proportions shifted by total chest irradiation but failed to perform radioprotection in gut microbiota-deleted mice. ImP, the downstream metabolite of l-Histidine, accumulated in peripheral blood and lung tissues following l-Histidine replenishment and protected against radiation-induced lung and heart toxicity. Orally gavaged ImP could not enter into the circulatory system in mice through an antibiotic cocktail treatment. Importantly, ImP inhibited pyroptosis to nudge lung cell proliferation after radiation challenge. Together, our findings pave a novel method of protection against cardiopulmonary complications intertwined with radiotherapy in pre-clinical settings and underpin the idea that gut microbiota-produced l-Histidine and ImP are promising radioprotective agents.

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Dusp6 Depletion Enhances Gut Barrier Integrity and Microbiota Eubiosis Against Dextran Sulfate Sodium-Induced Colitis in Mice

10.21203/rs.3.rs-44154/v1 ◽

2020 ◽

Author(s):

Cherng-Shyang Chang ◽

Yi-Chu Liao ◽

Chih-Ting Huang ◽

Chiao-Mei Lin ◽

Chantal Hoi Yin Cheung ◽

...

Keyword(s):

Gut Microbiota ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Protective Effects ◽

Gut Barrier ◽

Barrier Integrity ◽

Altered Glucose ◽

Deficient Mice

Abstract Background: Leaky gut and microbiota dysbiosis have been linked to many chronic inflammatory diseases. Strengthening the gut epithelial barrier is a novel but overlooked strategy for management of gut microbiota-associated illnesses. Results: Using the dextran sulfate sodium (DSS)-induced gut barrier injury-based colitis model, we found that DSS-induced weight loss, rectal bleeding, and colonic epithelium damage were ameliorated in dual-specificity phosphatase 6 (Dusp6)-deficient mice. These protective effects could be attributed to the enhanced colon barrier integrity conferred by Dusp6-deficiency. Consistently, DUSP6 mutation in Caco-2 cells elevated transepithelial electrical resistance, enhanced tight-junctions, and increased expression of microvilli-associated genes. DUSP6-deficient Caco-2 cells also showed increased mitochondrial oxygen consumption accompanied by altered glucose metabolism and decreased glycolysis. Remarkably, our microbiome analysis found that Dusp6-deficient mice harbored fewer pathobionts and facultative anaerobes and more obligate anaerobes than wild-type mice after DSS treatment. Our cohousing and fecal microbiota transplantation experiments demonstrated that the gut/fecal microbiota derived from Dusp6-deficient mice also conferred protection against colitis.Conclusion: We have thus identified Dusp6 deficiency as beneficial in enhancing gut barrier integrity, elevating epithelial phosphoxidation, and maintaining the gut microbiota eubiosis necessary to protect against colitis.

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Exploration of the Relationship Between Gut Microbiota and Polycystic Ovary Syndrome (PCOS): a Review

Geburtshilfe und Frauenheilkunde ◽

10.1055/a-1081-2036 ◽

2020 ◽

Vol 80 (02) ◽

pp. 161-171 ◽

Cited By ~ 6

Author(s):

Xiaoxuan Zhao ◽

Yuepeng Jiang ◽

Hongyan Xi ◽

Lu Chen ◽

Xiaoling Feng

Keyword(s):

Metabolic Syndrome ◽

Polycystic Ovary Syndrome ◽

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Polycystic Ovary ◽

Treatment Options ◽

Short Chain Fatty Acids ◽

Fecal Microbiota ◽

Ovary Syndrome ◽

New Ideas

AbstractPolycystic ovary syndrome (PCOS) is an endocrine and metabolic syndrome (MS) with a complex etiology, and its pathogenesis is not yet clear. In recent years, the correlation between gut microbiota (GM) and metabolic disease has become a hot topic in research, leading to a number of new ideas about the etiology and pathological mechanisms of PCOS. The literature shows that GM can cause insulin resistance, hyperandrogenism, chronic inflammation and metabolic syndrome (obesity, diabetes) and may contribute to the development of PCOS by influencing energy absorption, the pathways of short chain fatty acids (SCFA), lipopolysaccharides, choline and bile acids, intestinal permeability and the brain–gut axis. As part of the treatment of PCOS, fecal microbiota transplantation, supplementation with prebiotics and traditional Chinese medicine can be used to regulate GM and treat disorders. This article reviews possible mechanisms and treatment options for PCOS, based on methods which target the GM, and offers new ideas for the treatment of PCOS.

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Malnutrition Accelerates Colorectal Cancer Progression through Macrophage Activated by B Cells Immune via Gut Microbiota

10.21203/rs.3.rs-51243/v1 ◽

2020 ◽

Author(s):

Xu Chao ◽

Li Dechuan ◽

Wang Ziwei ◽

Wang Yan ◽

Xu Lu ◽

...

Keyword(s):

Colorectal Cancer ◽

B Cells ◽

Gut Microbiota ◽

Cancer Progression ◽

Gut Microbiome ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Nutrition Status ◽

Enzyme Linked Immunosorbent Assay ◽

Mice Model

Abstract Background: Malnutrition threatened the clinical outcomes of colorectal cancer (CRC) by reducing patients’ responses to anti-cancer treatments and ultimately shortening thesurvival time. Recently malnutrition has been confirmed to play an important role in CRC progress via gut microbiota. However, roles of gut microbiota in the immunopathogenesis of malnutrition and its underlying mechanisms remain inconclusive. Methods: Patient-Generated Subjective Global Assessment (PG-SGA) was performed to determine the nutrition status in colon cancer patients. 16srRNA sequencing was prepared to explore the dramatic variation of the fecal microbiota among patients with different nutrition status. Fecal microbiota transplantation was used to transplant into C57BL/6J mice model and DSS/AOM mice model. Immunohistochemistry and immunofluorescence were applied to test the CD makers. Fluorescence-activated cell sorting was also prepared to explore the B cells and macrophage from serum and tissues. Enzyme-linked immunosorbent assay and qPCR were used to determine the expression level of cytokines.Results: In this work, we found the specific microbiota species including Atopobium.vaginae, Selenomonas.sputigena and Faecalibacterium.prausnitzii, which may be considered as the diagnostic biomarkers to help improve poor prognosis in CRC. These microbiota were found to be protumorigenic and adversely affect the nutritional status and overall survival of the animal models. More importantly, our evidence suggesting that these fecal microbiota recruited B cells and macrophage to activate the specific tumor immune in CRC. Depletion of B cells significantly suppressed fecal microbiota induced-M2b polarization, as well as the protumorigenic activity of tumor-associated macrophages in vivo.Conclusion: gut microbiome in CRC under malnutrition status could upregulate the activity of B cells and protumorigenic macrophage in CRC. Gut microbiome intervention could be a feasible approach to malnutrition-related CRC treatment.

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Oridonin Alters Hepatic Urea Cycle via Gut Microbiota and Protects against Acetaminophen-Induced Liver Injury

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/3259238 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Mu-keng Hong ◽

Hai-hua Liu ◽

Gui-hong Chen ◽

Jun-qing Zhu ◽

Song-yuan Zheng ◽

...

Keyword(s):

Liver Injury ◽

Gut Microbiota ◽

Urea Cycle ◽

Fecal Microbiota Transplantation ◽

Redox Homeostasis ◽

Fecal Microbiota ◽

Hepatic Tissue ◽

Western World ◽

Related Factor ◽

Protective Effects

Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the western world. Oridonin (OD), which is the major active ingredient of the traditional Chinese medicine Rabdosia rubescens, reportedly exerts anti-inflammatory and antioxidative effects. Here, we first find that OD protects against APAP-induced hepatotoxicity. The results of hepatic tissue-associated RNA-seq and metabolomics showed that the protective effects of OD were dependent upon urea cycle regulation. And such regulation of OD is gut microbiota partly dependent, as demonstrated by fecal microbiota transplantation (FMT). Furthermore, using 16S rRNA sequencing, we determined that OD significantly enriched intestinal Bacteroides vulgatus, which activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to regulate redox homeostasis against APAP by urea cycle. In conclusion, our study suggests that the Bacteroides vulgatus-urea cycle-Nrf2 axis may be a potential target for reducing APAP-induced liver injury, which is altered by OD.

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Interplay between the Gut Microbiota and Inflammatory Mediators in the Development of Colorectal Cancer

Cancers ◽

10.3390/cancers13040734 ◽

2021 ◽

Vol 13 (4) ◽

pp. 734

Author(s):

Gwangbeom Heo ◽

Yunna Lee ◽

Eunok Im

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Inflammatory Mediators ◽

Tumor Metastasis ◽

Intestinal Tract ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Therapeutic Interventions ◽

Potential Therapeutic Target ◽

Necrosis Factor

Inflammatory mediators modulate inflammatory pathways during the development of colorectal cancer. Inflammatory mediators secreted by both immune and tumor cells can influence carcinogenesis, progression, and tumor metastasis. The gut microbiota, which colonize the entire intestinal tract, especially the colon, are closely linked to colorectal cancer through an association with inflammatory mediators such as tumor necrosis factor, nuclear factor kappa B, interleukins, and interferons. This association may be a potential therapeutic target, since therapeutic interventions targeting the gut microbiota have been actively investigated in both the laboratory and in clinics and include fecal microbiota transplantation and probiotics.

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Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

Nutrients ◽

10.3390/nu13020690 ◽

2021 ◽

Vol 13 (2) ◽

pp. 690

Author(s):

Umair Shabbir ◽

Muhammad Sajid Arshad ◽

Aysha Sameen ◽

Deog-Hwan Oh

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Gut Microbiota ◽

Dietary Habits ◽

Inflammatory Responses ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Gut Dysbiosis ◽

Dynamic Population

The gut microbiota (GM) represents a diverse and dynamic population of microorganisms and about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest that the GM can influence the health of the host, and several factors can modify the GM composition, such as diet, drug intake, lifestyle, and geographical locations. Gut dysbiosis can affect brain immune homeostasis through the microbiota–gut–brain axis and can play a key role in the pathogenesis of neurodegenerative diseases, including dementia and Alzheimer’s disease (AD). The relationship between gut dysbiosis and AD is still elusive, but emerging evidence suggests that it can enhance the secretion of lipopolysaccharides and amyloids that may disturb intestinal permeability and the blood–brain barrier. In addition, it can promote the hallmarks of AD, such as oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, and ultimately the causation of neural death. Poor dietary habits and aging, along with inflammatory responses due to dysbiosis, may contribute to the pathogenesis of AD. Thus, GM modulation through diet, probiotics, or fecal microbiota transplantation could represent potential therapeutics in AD. In this review, we discuss the role of GM dysbiosis in AD and potential therapeutic strategies to modulate GM in AD.

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Gut microbiota restoration through fecal microbiota transplantation: a new atopic dermatitis therapy

Experimental & Molecular Medicine ◽

10.1038/s12276-021-00627-6 ◽

2021 ◽

Author(s):

Jong-Hwa Kim ◽

Kiyoung Kim ◽

Wonyong Kim

Keyword(s):

Atopic Dermatitis ◽

Mast Cells ◽

Gut Microbiota ◽

Immune Modulation ◽

Fecal Microbiota Transplantation ◽

Blood Parameters ◽

Fecal Microbiota ◽

Th1 And Th2 Cytokines ◽

Calprotectin Level ◽

Donor State

AbstractThe pathogenesis of atopic dermatitis (AD) involves complex factors, including gut microbiota and immune modulation, which remain poorly understood. The aim of this study was to restore gut microbiota via fecal microbiota transplantation (FMT) to ameliorate AD in mice. FMT was performed using stool from donor mice. The gut microbiota was characterized via 16S rRNA sequencing and analyzed using Quantitative Insights into Microbial Ecology 2 with the DADA2 plugin. Gut metabolite levels were determined by measuring fecal short-chain fatty acid (SCFA) contents. AD-induced allergic responses were evaluated by analyzing blood parameters (IgE levels and eosinophil percentage, eosinophil count, basophil percentage, and monocyte percentage), the levels of Th1 and Th2 cytokines, dermatitis score, and the number of mast cells in the ileum and skin tissues. Calprotectin level was measured to assess gut inflammation after FMT. FMT resulted in the restoration of gut microbiota to the donor state and increases in the levels of SCFAs as gut metabolites. In addition, FMT restored the Th1/Th2 balance, modulated Tregs through gut microbiota, and reduced IgE levels and the numbers of mast cells, eosinophils, and basophils. FMT is associated with restoration of gut microbiota and immunologic balance (Th1/Th2) along with suppression of AD-induced allergic responses and is thus a potential new therapy for AD.

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Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis

Biomedicines ◽

10.3390/biomedicines9020145 ◽

2021 ◽

Vol 9 (2) ◽

pp. 145

Author(s):

Julio Plaza-Díaz ◽

Patricio Solis-Urra ◽

Jerónimo Aragón-Vela ◽

Fernando Rodríguez-Rodríguez ◽

Jorge Olivares-Arancibia ◽

...

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Liver Steatosis ◽

Intestinal Barrier ◽

Fecal Microbiota ◽

Current Treatment ◽

Immune Defense ◽

Alcoholic Fatty Liver ◽

The Impact

Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).

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