Translocation Of Lipopolysaccharide Research Articles

High-fat diet led to testicular inflammation and ferroptosis via dysbiosis of gut microbes

The disorder of gut microbiota has negative impact on male reproductive, and testicular damage is associated with obesity. However, the detailed mechanism of gut microbiota on the obesity-induced testis injury are still unknown. Therefore, we constructed a mouse model to investigate the effects of obesity on testis injury. In this study, we found that HFD-induced obesity could disorder gut microbiota homeostasis, which increased the abundance of Brevundimonas, Desulfovibrionaceae_unclassified and Ralstonia, ultimately leading to the overproduction of lipopolysaccharides (LPS). Meanwhile, HFD-feeding promoted intestinal permeability via inhibiting expression of tight junction proteins (ZO-1, Occludin and Claudin) and reducing excretion of mucus, leading to translocation of LPS. The over-accumulation of LPS in the bloodstream triggered an inflammatory response by activating TLR4/NF-κB pathway in testis. On the other hand, the gut microbiota produced-LPS also could induce ferroptosis in testis, as reflected by enhancing iron content and lipid peroxidation (MDA), as well as decreasing ferroptosis-related proteins, including GPX4, FTH1 and SLC1A11. Moreover, inhibition of LPS ligand (TLR4) with Resatorvid (TAK-242) alleviated obesity-induced testis injury through suppression of inflammation and ferroptosis. In conclusion, this study provides novel insights into the underlying mechanisms of obesity–related testis injury induced by gut microbiota disorder via the gut–testis axis, thus offering potential targets to counteract obesity-induced male reproductive disorder.

Lipopolysaccharide, arbiter of the gut-liver axis, modulates hepatic cell pathophysiology in alcoholism.

Over the last four decades, clinical research and experimental studies have established that lipopolysaccharide (LPS)-a component of the outer membrane of gram-negative bacteria-is a potent hepatotoxic molecule in humans and animals. Alcohol abuse is commonly associated with LPS endotoxemia. This review highlights LPS molecular structures and modes of release from bacteria, plasma LPS concentrations, induction of microbiota dysbiosis, disruption of gut epithelial barrier, and translocation of LPS into the portal circulation impacting the pathophysiology of hepatic cells via the gut-liver axis. We describe and illustrate the portal vein circulation and its distributaries draining the gastrointestinal tract. We also elaborate on the gut-liver axis coupled with enterohepatic circulation that represents a bidirectional communication between the gut and liver. The review also updates the data on how circulating LPS is cleared in a coordinated effort between Kupffer cells, hepatocytes, and liver sinusoidal endothelial cells. Significantly, the article reviews and updates the modes/mechanisms of action by which LPS mediates the diverse pathophysiology of Kupffer cells, hepatocytes, sinusoidal endothelial cells, and hepatic stellate cells primarily in association with alcohol consumption. Specifically, we review the intricate linkages between ethanol, microbiota dysbiosis, LPS production, gut-liver axis, and pathophysiology of various hepatic cells. The maintenance of the gut barrier structural and functional integrity and microbiome homeostasis is essential in mitigating alcoholic liver disease and improving liver health.

Elevated lipopolysaccharide level is largely driven by time since symptom onset in acute ischemic stroke: the impact on clinical outcomes

BackgroundGut dysbiosis leading to increased intestinal barrier permeability and translocation of lipopolysaccharide (LPS) in the circulation has been demonstrated in patients with acute myocardial infarction and pulmonary embolism. ObjectivesWe investigated changes in circulating LPS concentrations in acute ischemic stroke (AIS) and their consequences, including prognosis. MethodsWe studied 98 AIS patients, aged 74 ± 12 years, including 74 (75.5%) thrombolysed individuals. We determined serum LPS and zonulin, a marker of gut permeability, along with protein carbonyl (PC), fibrin clot properties, and thrombin generation on admission, at 24 hours and 3 months. Stroke severity was assessed using the National Institutes of Health Stroke Scale. Stroke functional outcome using modified Rankin scale and stroke-related mortality were evaluated at 3 months. ResultsSerum LPS and zonulin levels on admission were associated with time since symptom onset (r = 0.57; P < .0001; and r = 0.40; P < .0001). Baseline LPS levels correlated with PC (r = 0.51; P < .0001) but not with coagulation and fibrinolysis markers. LPS levels increased at 24 hours in thrombolysed patients (P < .001) and correlated with the National Institutes of Health Stroke Scale score (r = 0.31; P = .002) and PC (r = 0.32; P = .0057). Both LPS and zonulin levels measured at 24 hours increased the odds of having unfavorable modified Rankin scale scores (odds ratio [OR], 1.22; 95% CI, 1.04-1.42; and OR, 2.36; 95% CI, 1.24-4.49 per unit). Elevated LPS level, but not zonulin, was associated with stroke-related mortality (OR, 1.26; 95% CI, 1.02-1.55 per unit). ConclusionIn AIS patients intestinal permeability is mainly driven by increasing time since the symptom onset. Our findings suggest that LPS, with a trend toward its further rise following thrombolysis, adversely affects neurologic functional outcomes and 3-month mortality.

Maslinic acid alleviates alcoholic liver injury in mice and regulates intestinal microbiota via the gut-liver axis.

Maslinic acid (MA), a pentacyclic triterpene acid, is widely distributed in natural plants and mainly found in the fruit and leaves of olives and hawthorn. MA has been reported as having many health-promoting functions, such as anticancer, anti-inflammation and neuroprotective activities. According to previous study, hawthorn extract has certain hepatoprotective effects. However, the detailed mechanism is still unclear, especially the effect of MA on gut microbiota. Our study reveals that MA effectively counteracts alcohol-induced liver injury and oxidative stress. It mitigates alcohol-induced intestinal barrier damage, reverses increased permeability and reduces translocation of lipopolysaccharide (LPS). This prevents LPS/Toll-like receptor 4 activation, leading to decreased TNF-α and IL-1β production. Furthermore, MA rebalances gut microbiota by reversing harmful bacterial abundance and enhancing beneficial bacteria post-alcohol consumption. MA, through modulation of gut microbiota, alleviates alcohol-induced liver injury via the gut-liver axis. These findings support the potential use of MA as a functional food ingredient for preventing or treating alcoholic liver disease. © 2024 Society of Chemical Industry.

Oleuropein, a Component of Extra Virgin Olive Oil, Improves Liver Steatosis and Lobular Inflammation by Lipopolysaccharides-TLR4 Axis Downregulation.

Gut-dysbiosis-induced lipopolysaccharides (LPS) translocation into systemic circulation has been suggested to be implicated in nonalcoholic fatty liver disease (NAFLD) pathogenesis. This study aimed to assess if oleuropein (OLE), a component of extra virgin olive oil, lowers high-fat-diet (HFD)-induced endotoxemia and, eventually, liver steatosis. An immunohistochemistry analysis of the intestine and liver was performed in (i) control mice (CTR; n = 15), (ii) high-fat-diet fed (HFD) mice (HFD; n = 16), and (iii) HFD mice treated with 6 µg/day of OLE for 30 days (HFD + OLE, n = 13). The HFD mice developed significant liver steatosis compared to the controls, an effect that was significantly reduced in the HFD + OLE-treated mice. The amount of hepatocyte LPS localization and the number of TLR4+ macrophages were higher in the HFD mice in the than controls and were lowered in the HFD + OLE-treated mice. The number of CD42b+ platelets was increased in the liver sinusoids of the HFD mice compared to the controls and decreased in the HFD + OLE-treated mice. Compared to the controls, the HFD-treated mice showed a high percentage of intestine PAS+ goblet cells, an increased length of intestinal crypts, LPS localization and TLR4+ expression, and occludin downregulation, an effect counteracted in the HFD + OLE-treated mice. The HFD-fed animals displayed increased systemic levels of LPS and zonulin, but they were reduced in the HFD + OLE-treated animals. It can be seen that OLE administration improves liver steatosis and inflammation in association with decreased LPS translocation into the systemic circulation, hepatocyte localization of LPS and TLR4 downregulation in HFD-induced mouse model of NAFLD.

Elaidic acid-induced intestinal barrier damage led to gut-liver axis derangement and triggered NLRP3 inflammasome in the liver of SD rats

Previous studies have shown that trans fatty acids (TFA) are associated with several chronic diseases, the gut microbiota is directly influenced by dietary components and linked to chronic diseases. Our research investigated the effects of elaidic acid (EA), a typical TFA, on the gut microbiota to understand the underlying mechanisms of TFA-related chronic diseases. 16S rDNA gene sequencing on faecal samples from Sprague-Dawley rats were performed to explore the composition change of the gut microbiota by EA gavage for 4 weeks. The results showed that the intake of EA increased the abundance of well-documented harmful bacteria, such as Proteobacteria, Anaerotruncus, Oscillibacter and Desulfovibrionaceae. Plus, EA induced translocation of lipopolysaccharides (LPS) and the above pathogenic bacteria, disrupted the intestinal barrier, led to gut-liver axis derangement and TLR4 pathway activation in the liver. Overall, EA induced intestinal barrier damage and regulated TLR4-MyD88-NF-κB/MAPK pathways in the liver of SD rats, leading to the activation of NLRP3 inflammasome and inflammatory liver damage.

Protective Effect of Egg Yolk Lipids against Dextran Sulfate Sodium-Induced Colitis: The Key Role of Gut Microbiota and Short-Chain Fatty Acids.

Egg yolk lipids significantly alleviate dextran sulfate sodium (DSS)-induced colitis by inhibiting NLRP3 inflammasome, reversing gut microbiota dysbiosis, and increasing short chain fatty acids (SCFAs) concentrations. However, the role of gut microbiota and the relationship between SCFAs and NLRP3 inflammasome are still unknown. Here, this study confirms that antibiotic treatment abolishes the protective effect of egg yolk lipids on DSS-induced colonic inflammation, intestinal barrier damage, and lipopolysaccharide translocation. Fecal microbiota transplantation also supports that egg yolk lipids alleviate colitis in a gut microbiota-dependent manner. Then, the study investigates the relationship between SCFAs and NLRP3 inflammasome, and finds that SCFAs significantly suppress colitis via inhibiting colonic NLRP3 inflammasome activation and proinflammatory cytokines secretions (interleukin, IL)-1β and IL-18, and combined treatment of SCFAs and MCC950 (NLRP3 inhibitor) shows a better activity against colitis and NLRP3 inflammasome activation. Together, these findings provide positive evidence for gut microbiorta-SCFAs-NLRP3 axis as a novel target involving in the therapy of inflammatory bowel disease.

Berberine alleviates concanavalin A-induced autoimmune hepatitis in mice by modulating the gut microbiota.

Autoimmune hepatitis (AIH) is an immune-mediated liver disease of unknown etiology accompanied by intestinal dysbiosis and a damaged intestinal barrier. Berberine (BBR) is a traditional antibacterial medicine that has a variety of pharmacological properties. It has been reported that BBR alleviates AIH, but relevant mechanisms remain to be fully explored. BBR was orally administered at doses of 100mg⋅kg-1⋅d-1 for 7 days to mice before concanavalin A-induced AIH model establishment. Histopathological, immunohistochemical, immunofluorescence, western blotting, ELISA, 16S rRNA analysis, flow cytometry, real-time quantitative PCR, and fecal microbiota transplantation studies were performed to ascertain BBR effects and mechanisms in AIH mice. We found that liver necrosis and apoptosis were decreased upon BBR administration; the levels of serum transaminase, serum lipopolysaccharide, liver proinflammatory factors TNF-α, interferon-γ, IL-1β, and IL-17A, and the proportion of Th17 cells in spleen cells were all reduced, while the anti-inflammatory factor IL-10 and regulatory T cell proportions were increased. Moreover, BBR treatment increased beneficial and reduced harmful bacteria in the gut. BBR also strengthened ileal barrier function by increasing the expression of the tight junction proteins zonula occludens-1 and occludin, thereby blocking lipopolysaccharide translocation, preventing lipopolysaccharide/toll-like receptor 4 (TLR4)/ NF-κB pathway activation, and inhibiting inflammatory factor production in the liver. Fecal microbiota transplantation from BBR to model mice also showed that BBR potentially alleviated AIH by altering the gut microbiota. BBR alleviated concanavalin A-induced AIH by modulating the gut microbiota and related immune regulation. These results shed more light on potential BBR therapeutic strategies for AIH.

Soy Protein Concentrate Diets Inversely Affect LPS-Binding Protein Expression in Colon and Liver, Reduce Liver Inflammation, and Increase Fecal LPS Excretion in Obese Zucker Rats.

Dietary soy protein and soy isoflavones have anti-inflammatory properties. Previously, we reported that feeding soy protein concentrate diet (SPC) with low or high isoflavone (LIF or HIF) to young (seven-week-old) obese (fa/fa) Zucker rats inhibits lipopolysaccharide (LPS) translocation and decreases liver inflammation compared to a casein control (CAS) diet. The current study investigated whether SPC-LIF and SPC-HIF diets would reduce liver inflammation in adult obese Zucker rats fed a CAS diet. A total of 21 six-week-old male obese (fa/fa) Zucker rats were given CAS diet for 8 weeks to develop obesity then randomly assigned to CAS, SPC-LIF, or SPC-HIF (seven rats/group) diet for an additional 10 weeks. The expression of LPS-translocation, inflammation, and intestinal permeability markers were quantified by qPCR in liver, visceral adipose tissue (VAT), and colon. LPS concentration was determined in both the colon content and fecal samples by a Limulus amebocyte lysate (LAL) test. SPC-LIF and SPC-HIF diets significantly decreased liver LPS-binding protein (LBP) expression compared to CAS diet (p < 0.01 and p < 0.05, respectively). SPC-HIF diet also significantly decreased liver MCP-1 and TNF-α expression (p < 0.05) and had a trend to decrease liver iNOS expression (p = 0.06). In the colon, SPC-HIF diet significantly increased LBP expression compared to CAS diet (p < 0.05). When samples from all three groups were combined, there was a negative correlation between colon LBP expression and liver LBP expression (p = 0.046). SPC diets did not alter the expression of intestinal permeability markers (i.e., occludin, claudin 3, and zonula occludens-1) in the colon or inflammation markers (i.e., TNF-α and iNOS) in VAT or the colon. LPS levels in the colon content did not differ between any groups. Fecal LPS levels were significantly higher in the SPC-LIF and SPC-HIF groups compared to the CAS group (p < 0.01). In conclusion, SPC, particularly SPC with HIF, reduces liver LBP expression and inflammation makers (i.e., TNF-α and MCP-1 expression) in adult obese Zucker rats, likely by reducing LPS translocation.

Protective Effect of Silibinin on Lipopolysaccharide-Induced Endotoxemia by Inhibiting Caspase-11-Dependent Cell Pyroptosis.

To explore the protective effect and the underlying mechanism of silibinin (SIB), one of the active compounds from Silybum marianum (L.) Gaertn in endotoxemia. Mouse peritoneal macrophage were isolated via intraperitoneally injection of BALB/c mice with thioglycolate medium. Cell viability was assessed using the cell counting kit-8, while cytotoxicity was determined through lactate dehydrogenase cytotoxicity assay. The protein expressions of interleukin (IL)-1 α, IL-1 β, and IL-18 were determined by enzyme-linked immunosorbent assay. Intracellular lipopolysaccharide (LPS) levels were measured by employing both the limulus amoebocyte lysate assay and flow cytometry. Additionally, proximity ligation assay was employed for the LPS and caspase-11 interaction. Mice were divided into 4 groups: the control, LPS, high-dose-SIB (100 mg/kg), and low-dose-SIB (100 mg/kg) groups (n=8). Zebrafish were divided into 4 groups: the control, LPS, high-dose-SIB (200 εmol/L), and low-dose-SIB (100 εmol/L) groups (n=30 for survival experiment and n=10 for gene expression analysis). The expression of caspase-11, gasdermin D (GSDMD), and N-GSDMD was determined by Western blot and the expressions of caspy2, gsdmeb, and IL-1 β were detected using quantitative real-time PCR. Histopathological observation was performed through hematoxylineosin staining, and protein levels in bronchoalveolar lavage fluid were quantified using the bicinchoninicacid protein assay. SIB noticeably decreased caspase-11 and GSDMD-mediated pyroptosis and suppressed the secretion of IL-1 α, IL-1 β, and IL-18 induced by LPS (P<0.05). Moreover, SIB inhibited the translocation of LPS into the cytoplasm and the binding of caspase-11 and intracellular LPS (P<0.05). SIB also attenuated the expression of caspase-11 and N-terminal fragments of GSDMD, inhibited the relative cytokines, prolonged the survival time, and up-regulated the survival rate in the endotoxemia models (P<0.05). SIB can inhibit pyroptosis in the LPS-mediated endotoxemia model, at least in part, by inhibiting the caspase-11-mediated cleavage of GSDMD. Additionally, SIB inhibits the interaction of LPS and caspase-11 and inhibits the LPS-mediated up-regulation of caspase-11 expression, which relieves caspase-11-dependent cell pyroptosis and consequently attenuates LPS-mediated lethality.

Endari treatment ameliorates sickle cell-related disruption in intestinal barrier functions and is associated with prolonged survival in sickle cell mice

ABSTRACT Background Endari (L-glutamine) is a conditional amino acid that reduces the frequency of vaso-occlusive crisis (VOC) in sickle cell disease (SCD). Aim To investigate whether Endari could ameliorate intestinal barrier function and improve survival outcomes in SCD. Methods We treated female Townes SCD mice with Endari and evaluated their intestinal barrier functions by measuring the recovery of orally administered fluorescein isothiocyanate (FITC)-conjugated dextran 4 kDa in serum, and serum intestinal fatty acid binding proteins (iFABP) and lipopolysaccharide (LPS) concentrations by ELISA. We also explored the impact the Endari has on the survival of the SCD mice that underwent repeated experimentally-induced VOC. Results Compared to SCD mice treated with water only, Endari-treated mice showed improved intestinal barrier functions, with decrease in the barrier permeability and reduction in the translocation of lipopolysaccharides from the intestinal lumen into the circulation. These changes occurred after only 4 weeks of Endari treatment. Improved intestinal barrier function was also associated with prolonged survival in Endari-treated SCD mice after repeated experimentally-induced VOC. Conclusion Our findings provide the evidence supporting the beneficial effects of Enadri in improving intestinal barrier function and associated survival outcomes in SCD.

Role of gut-derived bacterial lipopolysaccharide and peripheral TLR4 in immobilization stress-induced itch aggravation in a mouse model of atopic dermatitis

Psychological stress and intestinal leakage are key factors in atopic dermatitis (AD) recurrence and exacerbation. Here, we demonstrate the mechanism underlying bacterial translocation across intestinal epithelial barrier damaged due to stress and further aggravation of trimellitic anhydride (TMA)–induced itch, which remain unclear, in AD mice. Immobilization (IMO) stress exacerbated scratching bouts and colon histological damage, and increased serum corticosterone and lipopolysaccharide (LPS). Orally administered fluorescein isothiocyanate (FITC)-dextran and surgically injected (into the colon) Cy5.5-conjugated LPS were detected in the serum and skin after IMO stress, respectively. The relative abundance of aerobic or facultative anaerobic bacteria was increased in the colon mucus layer, and Lactobacillus murinus, E. coli, Staphylococcus nepalensis, and several strains of Bacillus sp. were isolated from the spleens and mesenteric lymph nodes. Oral antibiotics or intestinal permeability blockers, such as lubiprostone (Lu), 2,4,6-triaminopyrimidine (TAP) and ML-7, inhibited IMO stress-associated itch; however, it was reinduced through intradermal or i.p. injection of LPS without IMO stress. I.p. injection of TAK-242 (resatorvid), a TLR4 inhibitor, abrogated IMO stress-associated itch, which was also confirmed in TLR4-KO mice. IMO stress alone did not cause itch in naïve mice. IMO stress-induced itch aggravation in TMA-treated AD mice might be attributed to the translocation of gut-derived bacterial cells and LPS, which activates peripheral TLR4 signaling.

Redundant essentiality of AsmA-like proteins in Pseudomonas aeruginosa.

Given the importance of the outer membrane (OM) for viability and antibiotic resistance in Gram-negative bacteria, in the last decades, several studies have focused on the characterization of the systems involved in OM biogenesis, which have also been explored as targets for antibacterial drug development. However, the mechanism mediating translocation of glycerophospholipids (GPLs) to the OM remained unknown until recent studies provided evidence that AsmA-like proteins could be responsible for this process. Here, we demonstrate for the first time that AsmA-like proteins are essential and redundant for growth and OM integrity in a Gram-negative bacterium other than the model organism Escherichia coli and demonstrate that the human pathogen Pseudomonas aeruginosa has an additional essential AsmA-like protein that is not present in E. coli, thus expanding the range of AsmA-like proteins that play key functions in Gram-negative bacteria.

Gut-Liver Axis as a Therapeutic Target for Drug-Induced Liver Injury.

Drug-induced liver injury (DILI) is a liver disease that remains difficult to predict and diagnose, and the underlying mechanisms are yet to be fully clarified. The gut-liver axis refers to the reciprocal interactions between the gut and the liver, and its homeostasis plays a prominent role in maintaining liver health. It has been recently reported that patients and animals with DILI have a disrupted gut-liver axis, involving altered gut microbiota composition, increased intestinal permeability and lipopolysaccharide translocation, decreased short-chain fatty acids production, and impaired bile acid metabolism homeostasis. The present review will summarize the evidence from both clinical and preclinical studies about the role of the gut-liver axis in the pathogenesis of DILI. Moreover, we will focus attention on the potential therapeutic strategies for DILI based on improving gut-liver axis function, including herbs and phytochemicals, probiotics, fecal microbial transplantation, postbiotics, bile acids, and Farnesoid X receptor agonists.

Intestinal barrier biomarkers in clinical evaluation of patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is associated with chronic intestinal barrier dysfunction, though its non-invasive assessment remains challenging. This study aimed to determine how four putative circulating markers vary across differing states of intestinal inflammation and with therapy in patients with IBD. Plasma samples from one prospective cross-sectional and four longitudinal studies, including healthy controls, were analysed for markers of lipopolysaccharide translocation, lipopolysaccharide-binding protein (LBP) and soluble-CD14 (sCD14), and markers of epithelial injury, syndecan-1 and intestinal-type fatty acid-binding protein (IFABP). Inflammatory activity was determined using objective measures. Compared with healthy subjects, concentrations of LBP and sCD14 were higher in patients with active (P < 0.001) and severe ulcerative colitis (UC) (P < 0.0001) and active Crohn's disease (CD) (P < 0.001). In UC in remission, LBP was less than in active disease (P = 0.011) LBP levels decreased longitudinally before and after induction of medical therapy in patients with IBD (P = 0.030) and as severe UC was brought into remission at weeks 2 and 12 (P ≤ 0.022). Response to treatment was associated with higher baseline levels of LBP (P = 0.019) and soluble-CD14 (P = 0.014). Concentrations of syndecan-1 and IFABP were or tended to be lower in UC and CD in active disease and did not change with successful therapy. While markers of epithelial injury were subnormal with active disease and did not change with therapy, markers of lipopolysaccharide translocation directly reflected intestinal inflammation, reduced with successful therapy and predicted treatment response.

Chronic arsenic exposure-provoked biotoxicity involved in liver-microbiota-gut axis disruption in chickens based on multi-omics technologies

IntroductionArsenic has been ranked as the most hazardous substance by the U.S. Agency for Toxic Substances and Disease Registry. Environmental arsenic exposure-evoked health risks have become a vital public health concern worldwide owing to the widespread existence of arsenic. Multi-omics is a revolutionary technique to data analysis providing an integrated view of bioinformation for comprehensively and systematically understanding the elaborate mechanism of diseases. ObjectivesThis study aimed at uncovering the potential contribution of liver-microbiota-gut axis in chronic inorganic arsenic exposure-triggered biotoxicity in chickens based on multi-omics technologies. MethodsForty Hy-Line W-80 laying hens were chronically exposed to sodium arsenite with a dose-dependent manner (administered with drinking water containing 10, 20, or 30 mg/L arsenic, respectively) for 42 d, followed by transcriptomics, serum non-targeted metabolome, and 16S ribosomal RNA gene sequencing accordingly. ResultsArsenic intervention induced a serious of chicken liver dysfunction, especially severe liver fibrosis, simultaneously altered ileal microbiota populations, impaired chicken intestinal barrier, further drove enterogenous lipopolysaccharides translocation via portal vein circulation aggravating liver damage. Furtherly, the injured liver disturbed bile acids (BAs) homoeostasis through strongly up-regulating the BAs synthesis key rate-limiting enzyme CYP7A1, inducing excessive serum total BAs accumulation, accompanied by the massive synthesis of primary BA—chenodeoxycholic acid. Moreover, the concentrations of secondary BAs—ursodeoxycholic acid and lithocholic acid were markedly repressed, which might involve in the repressed dehydroxylation of Ruminococcaceae and Lachnospiraceae families. Abnormal BAs metabolism in turn promoted intestinal injury, ultimately perpetuating pernicious circle in chickens. Notably, obvious depletion in the abundance of four profitable microbiota, Christensenellaceae, Ruminococcaceae, Muribaculaceae, and Faecalibacterium, were correlated tightly with this hepato-intestinal circulation process in chickens exposed to arsenic. ConclusionOur study demonstrates that chronic inorganic arsenic exposure evokes liver-microbiota-gut axis disruption in chickens and establishes a scientific basis for evaluating health risk induced by environmental pollutant arsenic.

Egg Yolk Lipids Alleviated Dextran Sulfate Sodium-Induced Colitis by Inhibiting NLRP3 Inflammasome and Regulating Gut Microbiota.

The increasing incidence of inflammatory bowel disease (IBD) has become a global phenomenon. Egg yolk lipids are one of the essential dietary foods, but its effects on intestinal immunity remain unclear. Here, egg yolk lipids are obtained using ethanol extraction and a total of 601 kinds of lipids are detected via lipidomics, including 251 kinds of triglycerides, 133 kinds of phosphatidylcholines, 44 kinds of phosphatidylethanolamines. Then, the study finds that egg yolk lipids significantly alleviate dextran sulfate sodium-induced colitis and reduce the production of inflammatory factors. Meanwhile, egg yolk lipids also maintain intestinal barrier integrity and decrease lipopolysaccharide translocation by alleviating intestinal structure damage and increasing the numbers of goblet cells and mucin 2. Mechanistically, egg yolk lipids attenuate colitis by inhibiting the assembly and activation of NLRP3 inflammasome. Moreover, the study also finds that egg yolk lipids reverse gut microbiota dysbiosis referring to increased relative abundance of Bacteroides acidifaciens and decrease relative abundance of Akkermansia muciniphila, as well as increased short chain fatty acids concentration in the gut. Together, the study elucidates the anti-colitis effect of egg yolk lipids and provides positive evidences for egg yolk lipids involving in dietary strategy and IBD therapy.

Feeding soy protein concentrates with low or high isoflavone decreases liver inflammation by reducing lipopolysaccharide translocation

Lipopolysaccharide (LPS) translocation and inflammation contribute to the increased risk of chronic diseases, including non-alcoholic fatty liver disease (NAFLD), associated with obesity. Previously, we reported that feeding soy protein with high or low (negligible) isoflavone reduces liver steatosis in obese Zucker rats, and the reduced steatosis is accompanied by decreased serum C-reactive protein levels. The current study investigated the effect of feeding soy protein concentrate (SPC) with high or low isoflavone (HIF or LIF) on liver inflammation and LPS translocation in obese Zucker rats. Six-week-old male lean (L, n = 21) and obese (O, n = 21) Zucker rats were fed casein control, SPC-LIF, or SPC-HIF diets for 18 weeks. At the end of 18 weeks, the expression levels of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), inducible nitric oxide synthase (iNOS), arginase 1 (ARG1), lipopolysaccharide binding protein (LBP), myeloperoxidase (MPO), and sterol regulatory element-binding protein 1 (SREBP-1) were significantly higher in obese rats compared to lean rats. Compared to the casein control diet, both the SPC-LIF and SPC-HIF diets significantly decreased TNF-α, MCP-1, iNOS, and LBP expression in obese rats, which is accompanied by significantly less LPS staining in liver slides from SPC-LIF-and SPC-HIF-fed obese rats compared to the casein control diet-fed obese rats. Taken together, the SPC-LIF and SPC-HIF diets attenuated liver inflammation in obese Zucker rats, likely by decreasing LPS translocation.

4.25 SSRIs May Reduce Gut Bacterial Translocation of Lipopolysaccharides in Adolescents With Internalizing Disorders

4.25 SSRIs May Reduce Gut Bacterial Translocation of Lipopolysaccharides in Adolescents With Internalizing Disorders

Effect of intramammary lipopolysaccharide challenge after repeated intrauterine infusion of lipopolysaccharide on the inflammation status of goat mammary glands

Previous studies have shown that a single infusion of lipopolysaccharide (LPS) into the uterus induces mammary gland inflammation. However, repeated LPS infusions return the mammary glands to their basal state of inflammation. To confirm that this is a state of tolerance to LPS, we examined whether tolerance induced by repeated intrauterine LPS infusions limits mammary gland inflammation following subsequent intramammary LPS infusions. In the first experiment, three goats were treated with repeated intrauterine infusions of LPS dissolved in black ink for 5 consecutive days. Blood and milk samples were collected at 2, 4, 6, 12, 24, 48, 72, 96, and 120 h and smeared on glass slides to confirm the translocation of LPS from the uterus to the mammary gland. Black particles were detected in the blood and milk samples more than 2 h after the first infusion and in the connective tissue of the mammary gland after day 5. In the second experiment, goats were divided into two groups: an intrauterine infusion group (IU; n = 7) and a control group (CON; n = 6). The IU group received an intrauterine infusion of 100 μg of LPS in saline for 5 days. Subsequently, LPS was infused into the mammary glands of both groups to examine the effect of intrauterine treatment on the mammary inflammatory response after intramammary LPS infusion. Blood and milk samples were collected at 6, 12, and 24 h, and then daily until 7 d after the intramammary LPS challenge. Interestingly, a significant increase in the milk somatic cell count (SCC), IL-8, IL-1β, and TNF-α concentrations were observed in the CON group compared to the IU group. This suggests that pretreatment with repeated intrauterine infusions of LPS suppresses the inflammatory responses to subsequent intramammary LPS challenges.