Inulin supplementation ameliorates hyperuricemia and modulates gut microbiota in Uox-knockout mice

Abstract Purpose Inulin is a type of fermentable dietary fiber, which is non-digestible, and can improve metabolic function by modulating intestinal microbiota. This study aimed to evaluate the role of inulin in hyperuricemia and microbial composition of the gut microbiota in a mouse model of hyperuricemia established through knockout of Uox (urate oxidase) gene. Methods KO (Uox-knockout) and WT (wild-type) mice were given inulin or saline by gavage for 7 weeks. The effect of inulin to combat hyperuricemia was determined by assessing the changes in serum UA (uric acid) levels, inflammatory parameters, epithelial barrier integrity, fecal microbiota alterations, and SCFA (short-chain fatty acid) concentrations in KO mice. Results Inulin supplementation can effectively alleviate hyperuricemia, increase the expressions of ABCG2 in intestine, and downregulate expression and activity of hepatic XOD (xanthine oxidase) in KO mice. It was revealed that the levels of inflammatory cytokines and the LPS (lipopolysaccharide) were remarkably higher in the KO group than those in the WT group, indicating systemic inflammation of hyperuricemic mice, but inulin treatment ameliorated inflammation in KO mice. Besides, inulin treatment repaired the intestinal epithelial barrier as evidenced by increased levels of intestinal TJ (tight junction) proteins [ZO-1 (zonula occludens-1) and occluding] in KO mice. Moreover, serum levels of uremic toxins, including IS (indoxyl sulfate) and PCS (p-cresol sulfate), were reduced in inulin-treated KO mice. Further investigation unveiled that inulin supplementation enhanced microbial diversity and raised the relative abundance of beneficial bacteria, involving SCFAs-producing bacteria (e.g., Akkermansia and Ruminococcus). Additionally, inulin treatment increased the production of gut microbiota-derived SCFAs (acetate, propionate and butyrate concentrations) in KO mice, which was positively correlated with the effectiveness of hyperuricemia relief. Conclusions Our findings showed that inulin may be a promising therapeutic candidate for the treatment of hyperuricemia. Moreover, alleviation of hyperuricemia by inulin supplementation was, at least, partially conciliated by modulation of gut microbiota and its metabolites.

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Dysbiosis in Functional Bowel Disorders

Annals of Nutrition and Metabolism ◽

10.1159/000488773 ◽

2018 ◽

Vol 72 (4) ◽

pp. 296-306 ◽

Cited By ~ 14

Author(s):

Paul Enck ◽

Nazar Mazurak

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Healthy Person ◽

Fecal Microbiota ◽

Functional Bowel Disorders ◽

Microbial Composition ◽

Bowel Disorders ◽

Irritable Bowel ◽

Benign Disorders

Functional bowel disorders (FBD) resemble a group of diseases of the gastrointestinal (GI) tract that are without a clear pathogenesis; the best known is probably the “irritable bowel syndrome” (IBS). Only recently we have been able to explore the role of the gut microbiota in FBD due to progress in microbiological analytic techniques. There are different ways to explore the role of the gut microbiota and its dysbiosis in FBD. Comparison of the microbial composition in a group of patients with FBD, for example, with IBS to a group of healthy volunteers is one way. Studies have shown that the microbiota in FBD is different from that of healthy controls, but the recorded differences are not necessarily specific for FBD, they may also occur in other diseases. Another approach to explore the role of the gut microbiota in FBD is to challenge the existing “flora” with novel bacteria (probiotics) or with nutritional substrates that stimulate bacterial growth (prebiotics). More than 60 such trials including several thousand patients have been performed in IBS. These studies have produced mixed outcome: some probiotics appear to be better than others, and some appear to work only for a part of the IBS symptoms and not for all. An extreme form of this approach is the transfer of an entire microbiota from 1 healthy person to another, called fecal microbiota transplantation. This has rarely been tested in FBD but is not without risk in benign disorders.

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An Association of Gut Microbiota with Different Phenotypes in Chinese Patients with Rheumatoid Arthritis

Journal of Clinical Medicine ◽

10.3390/jcm8111770 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1770 ◽

Cited By ~ 11

Author(s):

Hsin-I Chiang ◽

Jian-Rong Li ◽

Chun-Chi Liu ◽

Po-Yu Liu ◽

Hsin-Hua Chen ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gut Microbiota ◽

Diversity Index ◽

Alpha Diversity ◽

Serum Levels ◽

Chinese Patients ◽

Microbial Composition ◽

Inflammatory Parameters ◽

Tnf Α ◽

Bacterial Dna Extraction

We aimed to investigate the association of gut microbiota with disease activity, inflammatory parameters, and auto-antibodies profile in rheumatoid arthritis (RA). A total of 138 RA patients and 21 healthy controls (HC) were enrolled. Fecal samples were collected for bacterial DNA extraction and 16S ribosome (r)RNA sequencing, followed by analyses of gut microbiota composition. Serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-17A were determined by using ELISA. Our results indicated that RA patients had lower diversity index, which reflects both evenness and richness of gut microbiota, compared to HC. The alpha-diversity was lower in anti-citrullinated peptide antibodies (ACPA)-positive patients than in HC. The phylum Verrucomicrobiae and genus Akkermansia were more abundant in patients compared to HC. There was increased relative abundance of Enterobacteriaceae as well as Klebsiella, and less abundance of Bifidobacterium in patients with high levels of TNF-α or IL-17A compared to those who had low levels of these cytokines. In addition, ACPA-positive patients had higher proportions of Blautia, Akkermansia, and Clostridiales than ACPA-negative patients. Gut dysbiosis in RA patients was presented as different microbial composition and its association with inflammatory parameters as well as ACPA seropositivity. These findings support the involvement of gut microbiota in RA pathogenesis.

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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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Fecal microbiota dynamics during disease activity and remission in newly diagnosed and established ulcerative colitis

Scientific Reports ◽

10.1038/s41598-021-87973-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lena Öhman ◽

Anders Lasson ◽

Anna Strömbeck ◽

Stefan Isaksson ◽

Marcus Hesselmar ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Disease Activity ◽

Temporal Dynamics ◽

Fecal Microbiota ◽

Disease Stage ◽

Dietary Interventions ◽

Microbial Composition ◽

Fecal Samples ◽

Specific Species

AbstractPatients with ulcerative colitis (UC) have an altered gut microbiota composition, but the microbial relationship to disease activity needs to be further elucidated. Therefore, temporal dynamics of the fecal microbial community during remission and flare was determined. Fecal samples were collected at 2–6 time-points from UC patients during established disease (cohort EST) and at diagnosis (cohort NEW). Sampling range for cohort EST was 3–10 months and for cohort NEW 36 months. Relapses were monitored for an additional three years for cohort EST. Microbial composition was assessed by Genetic Analysis GA-map Dysbiosis Test, targeting ≥ 300 bacteria. Eighteen patients in cohort EST (8 with maintained remission and 10 experiencing a flare), provided 71 fecal samples. In cohort NEW, 13 patients provided 49 fecal samples. The microbial composition showed no clustering related to disease activity in any cohort. Microbial dissimilarity was higher between than within patients for both cohorts, irrespective of presence of a flare. Microbial stability within patients was constant over time with no major shift in overall composition nor modification in the abundance of any specific species. Microbial composition was not affected by intensified medical treatment or linked to future disease course. Thus in UC, the gut microbiota is highly stable irrespective of disease stage, disease activity or treatment escalation. This suggests that prolonged dietary interventions or repeated fecal transplantations are needed to be able to induce permanent alterations of the gut microbiota.

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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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Lupus Gut Microbiota Transplants Cause Autoimmunity and Inflammation

10.1101/2021.08.15.456375 ◽

2021 ◽

Author(s):

Yiyangzi Ma ◽

Ruru Guo ◽

Yiduo Sun ◽

Xin Li ◽

Lun He ◽

...

Keyword(s):

Gut Microbiota ◽

Lupus Erythematosus ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Healthy Controls ◽

Germ Free ◽

Autoimmune Antibodies ◽

Expression Of Genes ◽

Rdna Sequencing

Background: The etiology of systemic lupus erythematosus (SLE) is multifactorial. Recently, growing evidence suggests that the microbiota plays a role in SLE, yet whether gut microbiota participates in the development of SLE remains largely unknown. To investigate this issue, we carried out 16s rDNA sequencing analyses in a cohort of 18 female un-treated active SLE patients and 7 female healthy controls, and performed fecal microbiota transplantation from patients and healthy controls to germ-free mice. Results: Compared to the healthy controls, we found no significant different microbial diversity but some significantly different species in SLE patients including Turicibacter genus and other 5 species. Fecal transfer from SLE patients to germ free (GF) C57BL/6 mice caused GF mice to develop a series of lupus-like phenotyptic features, which including an increased serum autoimmune antibodies, and imbalanced cytokines, altered distribution of immune cells in mucosal and peripheral immune response, and upregulated expression of genes related to SLE in recipient mice that received SLE fecal microbiota transplantation (FMT). Moreover, the metabolism of histidine was significantly altered in GF mice treated with SLE patient feces, as compared to those which received healthy fecal transplants. Conclusions: Overall, our results describe a causal role of aberrant gut microbiota in contributing to the pathogenesis of SLE. The interplay of gut microbial and histidine metabolism may be one of the mechanisms intertwined with autoimmune activation in SLE.

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Role of Biological Sex in the Cardiovascular-Gut Microbiome Axis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.759735 ◽

2022 ◽

Vol 8 ◽

Author(s):

Shuangyue Li ◽

Georgios Kararigas

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Microbial Composition ◽

Biological Sex ◽

Technological Advances ◽

Host Health ◽

Health And Disease ◽

And Function ◽

Insight Into

There has been a recent, unprecedented interest in the role of gut microbiota in host health and disease. Technological advances have dramatically expanded our knowledge of the gut microbiome. Increasing evidence has indicated a strong link between gut microbiota and the development of cardiovascular diseases (CVD). In the present article, we discuss the contribution of gut microbiota in the development and progression of CVD. We further discuss how the gut microbiome may differ between the sexes and how it may be influenced by sex hormones. We put forward that regulation of microbial composition and function by sex might lead to sex-biased disease susceptibility, thereby offering a mechanistic insight into sex differences in CVD. A better understanding of this could identify novel targets, ultimately contributing to the development of innovative preventive, diagnostic and therapeutic strategies for men and women.

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Role of MFG-E8 in Protection of Intestinal Epithelial Barrier Function and Attenuation of Intestinal Inflammation

MFG-E8 and Inflammation ◽

10.1007/978-94-017-8765-9_3 ◽

2014 ◽

pp. 55-63 ◽

Cited By ~ 1

Author(s):

Suhail Akhtar ◽

Xiao Wang ◽

Heng-Fu Bu ◽

Xiao-Di Tan

Keyword(s):

Barrier Function ◽

Intestinal Inflammation ◽

Epithelial Barrier ◽

Intestinal Epithelial ◽

Intestinal Epithelial Barrier ◽

Epithelial Barrier Function

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IRF3 prevents colorectal tumorigenesis via inhibiting the nuclear translocation of β-catenin

Nature Communications ◽

10.1038/s41467-020-19627-7 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Miao Tian ◽

Xiumei Wang ◽

Jihong Sun ◽

Wenlong Lin ◽

Lumin Chen ◽

...

Keyword(s):

Gut Microbiota ◽

Nuclear Translocation ◽

Negative Regulator ◽

Intestinal Epithelial ◽

Colorectal Tumorigenesis ◽

Genetic Ablation ◽

Prognosis Marker ◽

Immune Sensing ◽

Innate Immune Sensing

AbstractOccurrence of Colorectal cancer (CRC) is relevant with gut microbiota. However, role of IRF3, a key signaling mediator in innate immune sensing, has been barely investigated in CRC. Here, we unexpectedly found that the IRF3 deficient mice are hyper-susceptible to the development of intestinal tumor in AOM/DSS and Apcmin/+ models. Genetic ablation of IRF3 profoundly promotes the proliferation of intestinal epithelial cells via aberrantly activating Wnt signaling. Mechanically, IRF3 in resting state robustly associates with the active β-catenin in the cytoplasm, thus preventing its nuclear translocation and cell proliferation, which can be relieved upon microbe-induced activation of IRF3. In accordance, the survival of CRC is clinically correlated with the expression level of IRF3. Therefore, our study identifies IRF3 as a negative regulator of the Wnt/β-catenin pathway and a potential prognosis marker for Wnt-related tumorigenesis, and describes an intriguing link between gut microbiota and CRC via the IRF3-β-catenin axis.

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