scholarly journals Phenazines Modulate Gastrointestinal Metabolism and Microbiota

2021 ◽  
Author(s):  
Wenjing Peng ◽  
Hui Li ◽  
Xiaole Zhao ◽  
Bing Shao ◽  
Kui Zhu
Keyword(s):  
Gut Microbiota ◽  
Digestive Tract ◽  
Metabolic Disorder ◽  
Rational Design ◽  
Pathogenic Bacteria ◽  
Intestinal Barrier ◽  
Swine Model ◽  
Structural Skeleton ◽  
Gut Microbiota Dysbiosis

Abstract Background: Natural and synthetic phenazines are ubiquitously occurred in environment and have been used for various therapeutic purposes in human, animals and agriculture, and the widespread use makes residue problem in environment and foods increasingly serious. However, the metabolic and comprehensive impacts of phenazines on the digestive tract are poorly understood, particularly the microbial pyocyanin (PYO), the most representative phenazines produced by Pseudomonas . Here, we utilized PYO as the representative of phenazines to study the effects on digestive tract. Results: Metabolic kinetic analysis showed that PYO exhibited low oral bioavailability in both rats and swine model, revealing a restriction of PYO in gut and might cause impacts on digestive tract. PYO was subsequently found to induce intestinal barrier destruction including inflammation and reactive oxygen species (ROS) accumulation in duodenum. Microbiome analysis showed that PYO caused gut microbiota dysbiosis by decreasing the symbiotic bacteria and increasing the opportunistic pathogenic bacteria. Additionally, the integral and dysfunctional assessment of liver demonstrated that PYO induced liver inflammation and metabolic disorder. Metabolism analysis further confirmed that PYO could be metabolized by both gut microbiota and liver, and all metabolites retained the nitrogen-containing tricyclic structural skeleton of phenazines, which was the core bioactivity of phenazine compounds, indicating all the outcomes were due to the intrinsic characteristic of phenazine structure. Conclusions: PYO were low oral bioavailable and all the metabolites retained the nitrogen-containing tricyclic structural skeleton, final resulting in the damages to digestive tract including intestinal barrier destruction, gut microbiota dysbiosis, liver damages and metabolic disorder. These findings elucidated the effect of phenazines on digestive tract in vivo and shed light on the rational design of phenazines for the development and application of such compounds in future.

scholarly journals Antibiotic-induced rat gut microbiota dysbiosis and salmonella resistance

2021 ◽  
Vol 2 (4/S) ◽  
pp. 93-100
Author(s):  
Begzod Shokirov ◽  
Yulduz Halimova
Keyword(s):  
Gut Microbiota ◽  
Digestive Tract ◽  
Antibiotic Treatment ◽  
Pathogenic Bacteria ◽  
Size Structure ◽  
Lactobacillus Rhamnosus ◽  
Repeated Use ◽  
And Function ◽  
Rat Gut ◽  
Gut Microbiota Dysbiosis

Antibiotics are the most common medicines used to treat human infectious diseases. Based on their chemical structure, antibiotics mainly include the following categories: quinolones, β-lactams, macrolides, and aminoglycosides among others. The mechanism of different antibiotics varies, and there are four main mechanisms: inhibition of bacterial cell wall synthesis, interaction with cell membranes, interference with protein synthesis, and inhibition of nucleic acid replication and transcription. Antibiotics can act on pathogenic bacteria. Accordingly, antibiotics can also affect normal bacteria that colonize the human body. The size, structure, and function of the microbiota may change in response to antibiotic treatment. Significant changes in the human gut microbiota may be associated with repeated use of antibiotics [3]; in the following days, these changes were restored. However, little is known about comparing the response of the gut microbiota to antibiotic treatment. Probiotics are beneficial to the host when administered in adequate amounts. Lactobacillus rhamnosus was one of the most common probiotics studied by scientists regarding its culture, function, and metabolism [10]. However, the effect of L. rhamnosus present in the gut microbiota on the host's susceptibility to pathogenic bacteria after taking antibiotics has rarely been discussed. In our current study, rats were given two types of antibiotics, namely vancomycin and ampicillin, and their oral and intestinal microbiota was observed at 3 time points.  The rats were treated with antibiotics or L. rhamnosus, and then infected with Salmonella entericaserovarTyphimurium (S. Typhimurium ) via a gastric tube. Fecal samples were then collected to determine the pathogenic load. Ampicillin and vancomycin act in different antimicrobial spectra and have different absorption in the digestive tract. In addition, the concentration of these antibiotics entering the digestive tract varies; these factors can affect the host microbiota. Thus, this study aimed to compare the effects of these antibiotics on the gut microbiota at normal doses, as well as to evaluate the differences in the results. The gut microbiota underwent dramatic changes during the administration period. Changes in the gut microbiota affected the host's susceptibility to pathogens when infected with bacteria due to changes in resistance to colonization.

scholarly journals Lactulose Improves Neurological Outcomes by Repressing Harmful Bacteria and Regulating Inflammatory Reactions in Mice After Stroke

2021 ◽  
Vol 11 ◽  
Author(s):  
Quan Yuan ◽  
Ling Xin ◽  
Song Han ◽  
Yue Su ◽  
Ruixia Wu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Metabolic Disorder ◽  
Intestinal Barrier ◽  
Neurological Function ◽  
Inflammatory Factors ◽  
Plasma Metabolites ◽  
Inflammatory Reactions ◽  
Rdna Sequencing ◽  
Photothrombotic Stroke ◽  
Gut Microbiota Dysbiosis

Background and ObjectiveGut microbiota dysbiosis following stroke affects the recovery of neurological function. Administration of prebiotics to counteract post-stroke dysbiosis may be a potential therapeutic strategy to improve neurological function. We aim to observe the effect of lactulose on neurological function outcomes, gut microbiota composition, and plasma metabolites in mice after stroke.MethodsMale C57BL/6 mice (20–25 g) were randomly divided into three groups: healthy control, photothrombotic stroke + triple-distilled water, and photothrombotic stroke + lactulose. After 14 consecutive days of lactulose administration, feces, plasma, and organs were collected. 16S rDNA sequencing, plasma untargeted metabolomics, qPCR, flow cytometry and Elisa were performed.ResultsLactulose supplementation significantly improved the functional outcome of stroke, downregulated inflammatory reaction, and increased anti-inflammatory factors in both the brain and gut. In addition, lactulose supplementation repaired intestinal barrier injury, improved gut microbiota dysbiosis, and partially amended metabolic disorder after stroke.ConclusionLactulose promotes functional outcomes after stroke in mice, which may be attributable to repressing harmful bacteria, and metabolic disorder, repairing gut barrier disruption, and reducing inflammatory reactions after stroke.

scholarly journals A Review on Gut Remediation of Selected Environmental Contaminants: Possible Roles of Probiotics and Gut Microbiota

Nutrients ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 22 ◽  
Author(s):  
Pengya Feng ◽  
Ze Ye ◽  
Apurva Kakade ◽  
Amanpreet Virk ◽  
Xiangkai Li ◽  
...  
Keyword(s):  
Heavy Metals ◽  
Gut Microbiota ◽  
Pathogenic Bacteria ◽  
Environmental Contaminants ◽  
Intestinal Barrier ◽  
Probiotic Bacteria ◽  
Intestinal Barrier Function ◽  
Primary Concern ◽  
Bacterial Strains

Various environmental contaminants including heavy metals, pesticides and antibiotics can contaminate food and water, leading to adverse effects on human health, such as inflammation, oxidative stress and intestinal disorder. Therefore, remediation of the toxicity of foodborne contaminants in human has become a primary concern. Some probiotic bacteria, mainly Lactobacilli, have received a great attention due to their ability to reduce the toxicity of several contaminants. For instance, Lactobacilli can reduce the accumulation and toxicity of selective heavy metals and pesticides in animal tissues by inhibiting intestinal absorption of contaminants and enhancing intestinal barrier function. Probiotics have also shown to decrease the risk of antibiotic-associated diarrhea possibly via competing and producing antagonistic compounds against pathogenic bacteria. Furthermore, probiotics can improve immune function by enhancing the gut microbiota mediated anti-inflammation. Thus, these probiotic bacteria are promising candidates for protecting body against foodborne contaminants-induced toxicity. Study on the mechanism of these beneficial bacterial strains during remediation processes and particularly their interaction with host gut microbiota is an active field of research. This review summarizes the current understanding of the remediation mechanisms of some probiotics and the combined effects of probiotics and gut microbiota on remediation of foodborne contaminants in vivo.

scholarly journals Constipation induced gut microbiota dysbiosis exacerbates experimental autoimmune encephalomyelitis in C57BL/6 mice

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiuli Lin ◽  
Yingying Liu ◽  
Lili Ma ◽  
Xiaomeng Ma ◽  
Liping Shen ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Gut Microbiota ◽  
Blood Brain Barrier ◽  
Intestinal Barrier ◽  
Brain Barrier ◽  
Autoimmune Encephalomyelitis ◽  
Gm Csf ◽  
Blood Brain ◽  
Gut Microbiota Dysbiosis ◽  
Experimental Autoimmune

Abstract Background Constipation is a common gastrointestinal dysfunction which has a potential impact on people's immune state and their quality of life. Here we investigated the effects of constipation on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Methods Constipation was induced by loperamide in female C57BL/6 mice. The alternations of gut microbiota, permeability of intestinal barrier and blood–brain barrier, and histopathology of colon were assessed after constipation induction. EAE was induced in the constipation mice. Fecal microbiota transplantation (FMT) was performed from constipation mice into microbiota-depleted mice. Clinical scores, histopathology of inflammation and demyelination, Treg/Th17 and Treg17/Teff17 imbalance both in the peripheral lymphatic organs and central nervous system, cytokines include TGF-β, GM-CSF, IL-10, IL-17A, IL-17F, IL-21, IL-22, and IL-23 in serum were assessed in different groups. Results Compared with the vehicle group, the constipation mice showed gut microbiota dysbiosis, colon inflammation and injury, and increased permeability of intestinal barrier and blood–brain barrier. We found that the clinical and pathological scores of the constipation EAE mice were severer than that of the EAE mice. Compared with the EAE mice, the constipation EAE mice showed reduced percentage of Treg and Treg17 cells, increased percentage of Th17 and Teff17 cells, and decreased ratio of Treg/Th17 and Treg17/Teff17 in the spleen, inguinal lymph nodes, brain, and spinal cord. Moreover, the serum levels of TGF-β, IL-10, and IL-21 were decreased while the GM-CSF, IL-17A, IL-17F, IL-22, and IL-23 were increased in the constipation EAE mice. In addition, these pathological processes could be transferred via their gut microbiota. Conclusions Our results verified that constipation induced gut microbiota dysbiosis exacerbated EAE via aggravating Treg/Th17 and Treg17/Teff17 imbalance and cytokines disturbance in C57BL/6 mice.

scholarly journals The DNA Sensor AIM2 Protects against Streptozotocin-Induced Type 1 Diabetes by Regulating Intestinal Homeostasis via the IL-18 Pathway

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 959 ◽  
Author(s):  
Jefferson Antônio Leite ◽  
Gabriela Pessenda ◽  
Isabel C. Guerra-Gomes ◽  
Alynne Karen Mendonça de Santana ◽  
Camila André Pereira ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Gut Microbiota ◽  
Bacterial Translocation ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Dna Sensor ◽  
Proinflammatory Response

Pattern recognition receptors (PRRs), such as Nod2, Nlrp3, Tlr2, Trl4, and Tlr9, are directly involved in type 1 diabetes (T1D) susceptibility. However, the role of the cytosolic DNA sensor, AIM2, in T1D pathogenesis is still unknown. Here, we demonstrate that C57BL/6 mice lacking AIM2 (AIM2−/−) are prone to streptozotocin (STZ)-induced T1D, compared to WT C57BL/6 mice. The AIM2−/− mice phenotype is associated with a greater proinflammatory response in pancreatic tissues, alterations in gut microbiota and bacterial translocation to pancreatic lymph nodes (PLNs). These alterations are related to an increased intestinal permeability mediated by tight-junction disruption. Notably, AIM2−/− mice treated with broad-spectrum antibiotics (ABX) are protected from STZ-induced T1D and display a lower pancreatic proinflammatory response. Mechanistically, the AIM2 inflammasome is activated in vivo, leading to an IL-18 release in the ileum at 15 days after an STZ injection. IL-18 favors RegIIIγ production, thus mitigating gut microbiota alterations and reinforcing the intestinal barrier function. Together, our findings show a regulatory role of AIM2, mediated by IL-18, in shaping gut microbiota and reducing bacterial translocation and proinflammatory response against insulin-producing β cells, which ultimately results in protection against T1D onset in an STZ-induced diabetes model.

scholarly journals Effects of Dietary Fibres on Acute Indomethacin-Induced Intestinal Hyperpermeability in the Elderly: A Randomised Placebo Controlled Parallel Clinical Trial

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1954
Author(s):  
John-Peter Ganda Mall ◽  
Frida Fart ◽  
Julia A. Sabet ◽  
Carl Mårten Lindqvist ◽  
Ragnhild Nestestog ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
The Elderly ◽  
Intestinal Barrier Function ◽  
Elderly Subjects ◽  
Microbiota Composition ◽  
Dietary Fibres ◽  
Gut Microbiota Composition

The effect of dietary fibres on intestinal barrier function has not been well studied, especially in the elderly. We aimed to investigate the potential of the dietary fibres oat β-glucan and wheat arabinoxylan to strengthen the intestinal barrier function and counteract acute non-steroid anti-inflammatory drug (indomethacin)-induced hyperpermeability in the elderly. A general population of elderly subjects (≥65 years, n = 49) was randomised to a daily supplementation (12g/day) of oat β-glucan, arabinoxylan or placebo (maltodextrin) for six weeks. The primary outcome was change in acute indomethacin-induced intestinal permeability from baseline, assessed by an in vivo multi-sugar permeability test. Secondary outcomes were changes from baseline in: gut microbiota composition, systemic inflammatory status and self-reported health. Despite a majority of the study population (85%) showing a habitual fibre intake below the recommendation, no significant effects on acute indomethacin-induced intestinal hyperpermeability in vivo or gut microbiota composition were observed after six weeks intervention with either dietary fibre, compared to placebo.

Benzene exposure induces gut microbiota dysbiosis and metabolic disorder in mice

2020 ◽  
Vol 705 ◽  
pp. 135879 ◽  
Author(s):  
Rongli Sun ◽  
Kai Xu ◽  
Shuangbin Ji ◽  
Yunqiu Pu ◽  
Zhaodi Man ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Metabolic Disorder ◽  
Benzene Exposure ◽  
Gut Microbiota Dysbiosis

scholarly journals The Effects of Iron and Zinc Biofortified Foods on Gut Microbiome, In Vivo (Gallus gallus): Systematic Analysis

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1324-1324
Author(s):  
Robert Rossi ◽  
Nikita Agarwal ◽  
Jacquelyn Cheng
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Pathogenic Bacteria ◽  
Experimental Studies ◽  
Short Chain Fatty Acids ◽  
Gallus Gallus ◽  
Systematic Analysis ◽  
Micronutrient Status ◽  
Iron And Zinc

Abstract Objectives Systematically analyze in-vivo (Gallus gallus) experimental studies that evaluate the effects of Fe and Zn biofortified foods or their derivatives on gut microbiota modulation. Methods The review was carried out in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) guidelines. Two researchers independently performed the data search at PubMed, Web of Science, Science Direct, and Scopus databases for experimental studies conducted in animal models published from January 2010 until December 2020. Five studies from the collection of 592 were selected based on the inclusion and exclusion criteria and analyzed. Results The studies indicated the dietary consumption of about 50% Fe and Zn biofortified foods provided several health benefits and improved the gut microbiome. Consumption of Fe and Zn biofortified foods was linked to increased abundance and capacity of short chain fatty acids and lactic acid producing bacteria, resulting in improved micronutrient solubility and absorption in the host. Further, a decrease in potentially pathogenic bacteria such as Streptococcus, Escherichia, and Enterobacter was linked to the consumption of Fe and Zn biofortified foods. Conclusions Dietary deficiencies of iron and zinc are common health concerns worldwide. Bacteria that colonize the gastrointestinal tract depend on micronutrients to maintain their activities, and gut microbiota compositional analysis may be an effective tool to assess host micronutrient status. This review suggests that Fe and Zn biofortified foods utilization positively restructures the gut microbiome and improves micronutrient absorption, thereby improving human health in vulnerable populations and maintaining micronutrient status in healthy populations. Further clinical and animal studies are needed to support the effects mentioned above. Funding Sources N/A.

scholarly journals Qing-Re-Xiao-Zheng Formula Modulates Gut Microbiota and Inhibits Inflammation in Mice With Diabetic Kidney Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Yabin Gao ◽  
Ruibing Yang ◽  
Lan Guo ◽  
Yaoxian Wang ◽  
Wei Jing Liu ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Gut Microbiota ◽  
Diabetic Kidney Disease ◽  
Inflammatory Responses ◽  
Protective Effects ◽  
Mice Model ◽  
Diabetic Kidney ◽  
Metabolic Inflammation ◽  
Gut Microbiota Dysbiosis

Evidence indicates that the metabolic inflammation induced by gut microbiota dysbiosis contributes to diabetic kidney disease. Prebiotic supplementations to prevent gut microbiota dysbiosis, inhibit inflammatory responses, and protect the renal function in DKD. Qing-Re-Xiao-Zheng formula (QRXZF) is a Traditional Chinese Medicine (TCM) formula that has been used for DKD treatment in China. Recently, there are growing studies show that regulation of gut microbiota is a potential therapeutic strategy for DKD as it is able to reduce metabolic inflammation associated with DKD. However, it is unknown whether QRXZF is effective for DKD by regulating of gut microbiota. In this study, we investigated the reno-protective effect of QRXZF by exploring its potential mechanism between gut microbiota and downstream inflammatory pathways mediated by gut-derived lipopolysaccharide (LPS) in the kidney. High-fat diet (HFD) and streptozotocin injection-induced DKD mice model was established to assess the QRXZF effect in vivo. Mice treated with QRXZF for 8 weeks had significantly lower levels of urinary albumin, serum cholesterol and triglycerides. The renal injuries observed through histological analysis were attenuated as well. Also, mice in the QRXZF group had higher levels of Zonula occludens protein-1 (ZO-1) expression, lower levels of serum fluorescein-isothiocyanate (FITC)-dextran and less-damaged colonic mucosa as compared to the DKD group, implying the benefit role for the gut barrier integrity. QRXZF treatment also reversed gut dysbiosis and reduced levels of gut-derived LPS. Notably, the expression of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB), which are important inflammation pathways in DKD, were suppressed in the QRXZF groups. In conclusion, our results indicated that the reno-protective effects of QRXZF was probably associated with modulating gut microbiota and inhibiting inflammatory responses in the kidney.

scholarly journals Lactobacillus gallinarum modulates the gut microbiota and produces anti-cancer metabolites to protect against colorectal tumourigenesis

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323951
Author(s):  
Naoki Sugimura ◽  
Qing Li ◽  
Eagle Siu Hong Chu ◽  
Harry Cheuk Hay Lau ◽  
Winnie Fong ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cell Proliferation ◽  
Gut Microbiota ◽  
Pathogenic Bacteria ◽  
Culture Supernatant ◽  
Suppressive Effect ◽  
Cell Cycle Distribution ◽  
Metagenomic Sequencing

ObjectiveUsing faecal shotgun metagenomic sequencing, we identified the depletion of Lactobacillus gallinarum in patients with colorectal cancer (CRC). We aimed to determine the potential antitumourigenic role of L. gallinarum in colorectal tumourigenesis.DesignThe tumor-suppressive effect of L. gallinarum was assessed in murine models of CRC. CRC cell lines and organoids derived from patients with CRC were cultured with L. gallinarum or Escherichia coli MG1655 culture-supernatant to evaluate cell proliferation, apoptosis and cell cycle distribution. Gut microbiota was assessed by 16S ribosomal DNA sequencing. Antitumour molecule produced from L. gallinarum was identified by liquid chromatography mass spectrometry (LC-MS/MS) and targeted mass spectrometry.ResultsL. gallinarum significantly reduced intestinal tumour number and size compared with E. coli MG1655 and phosphate-buffered saline in both male and female murine intestinal tumourigenesis models. Faecal microbial profiling revealed enrichment of probiotics and depletion of pathogenic bacteria in L. gallinarum-treated mice. Culturing CRC cells with L. gallinarum culture-supernatant (5%, 10% and 20%) concentration-dependently suppressed cell proliferation and colony formation. L. gallinarum culture-supernatant significantly promoted apoptosis in CRC cells and patient-derived CRC organoids, but not in normal colon epithelial cells. Only L. gallinarum culture-supernatant with fraction size <3 kDa suppressed proliferation in CRC cells. Using LC-MS/MS, enrichments of indole-3-lactic acid (ILA) was identified in both L. gallinarum culture-supernatant and the gut of L. gallinarum-treated mice. ILA displayed anti-CRC growth in vitro and inhibited intestinal tumourigenesis in vivo.ConclusionL. gallinarum protects against intestinal tumourigenesis by producing protective metabolites that can promote apoptosis of CRC cells.

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