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.

Partially hydrolyzed guar gum attenuates non-alcoholic fatty liver disease in mice through the gut-liver axis

BACKGROUND The gut-liver axis has attracted much interest in the context of chronic liver disease pathogenesis.Prebiotics such as dietary fibers were shown to attenuate non-alcoholic fatty liver disease(NAFLD)by modulating gut microbiota.Partially hydrolyzed guar gum(PHGG),a water-soluble dietary fiber,has been reported to alleviate the symptoms of various intestinal diseases and metabolic syndromes.However,its effects on NAFLD remain to be fully elucidated.To determine whether treatment with PHGG attenuates NAFLD development in mice through the gut-liver axis.METHODS Seven-week-old male C57BL/6J mice with increased intestinal permeability were fed a control or atherogenic(Ath)diet(a mouse model of NAFLD)for 8 wk,with or without 5%PHGG.Increased intestinal permeability was induced through chronic intermittent administration of low-dose dextran sulfate sodium.Body weight,liver weight,macroscopic findings in the liver,blood biochemistry[aspartate aminotransferase(AST)and alanine aminotransferase(ALT),total cholesterol,triglyceride,free fatty acids,and glucose levels],liver histology,myeloperoxidase activity in liver tissue,mRNA expression in the liver and intestine,serum endotoxin levels in the portal vein,intestinal permeability,and microbiota and short-chain fatty acid(SCFA)profiles in the cecal samples were investigated.RESULTS Mice with increased intestinal permeability subjected to the Ath diet showed significantly increased serum AST and ALT levels,liver fat accumulation,liver inflammatory(tumor necrosis factor-αand monocyte chemotactic protein-1)and fibrogenic(collagen 1a1 andαsmooth muscle actin)marker levels,and liver myeloperoxidase activity,which were significantly attenuated by PHGG treatment.Furthermore,the Ath diet combined with increased intestinal permeability resulted in elevated portal endotoxin levels and activated toll-like receptor(TLR)4 and TLR9 expression,confirming that intestinal permeability was significantly elevated,as observed by evaluating the lumen-to-blood clearance of fluorescein isothiocyanate-conjugated dextran.PHGG treatment did not affect fatty acid metabolism in the liver.However,it decreased lipopolysaccharide signaling through the gut-liver axis.In addition,it significantly increased the abundance of cecal Bacteroides and Clostridium subcluster XIVa.Treatment with PHGG markedly increased the levels of SCFAs,particularly,butyric acid,acetic acid,propionic acid,and formic acid,in the cecal samples.CONCLUSION PHGG partially prevented NAFLD development in mice through the gut-liver axis by modulating microbiota and downstream SCFA profiles.

Overview of the microbiota in the gut-liver axis in viral B and C hepatitis

Viral B and C hepatitis are a major current health issue,both diseases having a chronic damaging effect on the liver and its functions.Chronic liver disease can lead to even more severe and life-threatening conditions,such as liver cirrhosis and hepatocellular carcinoma.Recent years have uncovered an important interplay between the liver and the gut microbiome:the gut-liver axis.Hepatitis B and C infections often cause alterations in the gut microbiota by lowering the levels of‘protective’gut microorganisms and,by doing so,hinder the microbiota ability to boost the immune response.Treatments aimed at restoring the gut microbiota balance may provide a valuable addition to current practice therapies and may help limit the chronic changes observed in the liver of hepatitis B and C patients.This review aims to summarize the current knowledge on the anatofunctional axis between the gut and liver and to highlight the influence that hepatitis B and C viruses have on the microbiota balance,as well as the influence of treatments aimed at restoring the gut microbiota on infected livers and disease progression.

L.reuteri ZJ617 inhibits inflammatory and autophagy signaling pathways in gut-liver axis in piglet induced by lipopolysaccharide

Background:This study investigated the protective effects of L.reuteri ZJ617 on intestinal and liver injury and the underlying mechanisms in modulating inflammatory,autophagy,and apoptosis signaling pathways in a piglet challenged with lipopolysaccharide(LPS).Methods:Duroc×Landrace×Large White piglets were assigned to 3 groups(n=6/group):control(CON)and LPS groups received oral phosphate-buffered saline for 2 weeks before intraperitoneal injection(i.p.)of physiological saline or LPS(25μg/kg body weight),respectively,while the ZJ617+LPS group was orally inoculated with ZJ617 for 2 weeks before i.p.of LPS.Piglets were sacrificed 4 h after LPS injection to determine intestinal integrity,serum biochemical parameters,inflammatory signaling involved in molecular and liver injury pathways.Results:Compared with controls,LPS stimulation significantly increased intestinal phosphorylated-p38 MAPK,phosphorylated-ERK and JNK protein levels and decreased IκBαprotein expression,while serum LPS,TNF-α,and IL-6 concentrations(P<0.05)increased.ZJ617 pretreatment significantly countered the effects induced by LPS alone,with the exception of p-JNK protein levels.Compared with controls,LPS stimulation significantly increased LC3,Atg5,and Beclin-1 protein expression(P<0.05)but decreased ZO-1,claudin-3,and occludin protein expression(P<0.05)and increased serum DAO and D-xylose levels,effects that were all countered by ZJ617 pretreatment.LPS induced significantly higher hepatic LC3,Atg5,Beclin-1,SOD-2,and Bax protein expression(P<0.05)and lower hepatic total bile acid(TBA)levels(P<0.05)compared with controls.ZJ617 pretreatment significantly decreased hepatic Beclin-1,SOD2,and Bax protein expression(P<0.05)and showed a tendency to decrease hepatic TBA(P=0.0743)induced by LPS treatment.Pretreatment of ZJ617 before LPS injection induced the production of 5 significant metabolites in the intestinal contents:capric acid,isoleucine 1TMS,glycerol-1-phosphate byproduct,linoleic acid,alanine-alanine(P<0.05).Conclusions:These results demonstrated that ZJ617 pretreatment alleviated LPS-induced intestinal tight junction protein destruction,and intestinal and hepatic inflammatory and autophagy signal activation in the piglets.

Gut-liver axis and probiotics: Their role in non-alcoholic fatty liver disease

The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease(NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies(e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth,specific gut microbiota and/or a"low bacterial richness"may play a role in obesity,metabolic syndrome,and fatty liver.Under conditions involving a damaged intestinal barrier("leaky gut"),the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors(e.g.,toll-like receptors),thus promoting the following cascade of events:oxidative stress,insulinresistance,hepatic inflammation,and fibrosis.We also discuss the possible modulation of gut microbiota by probiotics,as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies.Globally,this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.

Gut microbial dysbiosis associates hepatocellular carcinoma via the gut-liver axis

Background: Hepatocellular carcinoma(HCC) is one of the most common malignancies in the world. Gut microbiota has been demonstrated to play a critical role in liver inflammation, chronic fibrosis, liver cirrhosis, and HCC development through the gut-liver axis. Data sources: Recently there have been several innovative studies investigating gut microbial dysbiosismediated enhancement of HCC through the gut-liver axis. Literatures from January 1998 to January 2018 were searched in the Pub Med database using the keywords "gut microbiota" and "hepatocellular carcinoma" or "liver cancer", and the results of experimental and clinical studies were analyzed. Results: Gut microbial dysbiosis accompanies the progression of alcoholic liver disease, non-alcoholic fatty liver disease and liver cirrhosis, and promotes HCC progression in an experimental mouse model. The immune system and key factors such as Toll-like receptor 4 are involved in the process. There is evidence for gut microbial dysbiosis in hepatitis virus-related HCC patients. Conclusions: Gut microbial dysbiosis is closely associated with hepatic inflammation disease and HCC through the gut-liver axis. With the enhanced understanding of the interactions between gut microbiota and liver through the gut-liver axis, new treatment strategies for HCC are being developed.

Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia

A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin,activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis.

Gut-liver axis signaling in portal hypertension

Portal hypertension(PHT)in advanced chronic liver disease(ACLD)results from increased intrahepatic resistance caused by pathologic changes of liver tissue composition(structural component)and intrahepatic vasoconstriction(functional component).PHT is an important driver of hepatic decompensation such as development of ascites or variceal bleeding.Dysbiosis and an impaired intestinal barrier in ACLD facilitate translocation of bacteria and pathogen-associated molecular patterns(PAMPs)that promote disease progression via immune system activation with subsequent induction of proinflammatory and profibrogenic pathways.Congestive portal venous blood flow represents a critical pathophysiological mechanism linking PHT to increased intestinal permeability:The intestinal barrier function is affected by impaired microcirculation,neoangiogenesis,and abnormal vascular and mucosal permeability.The close bidirectional relationship between the gut and the liver has been termed“gut-liver axis”.Treatment strategies targeting the gut-liver axis by modulation of microbiota composition and function,intestinal barrier integrity,as well as amelioration of liver fibrosis and PHT are supposed to exert beneficial effects.The activation of the farnesoid X receptor in the liver and the gut was associated with beneficial effects in animal experiments,however,further studies regarding efficacy and safety of pharmacological FXR modulation in patients with ACLD are needed.In this review,we summarize the clinical impact of PHT on the course of liver disease,discuss the underlying pathophysiological link of PHT to gut-liver axis signaling,and provide insight into molecular mechanisms that may represent novel therapeutic targets.

Gut-liver axis improves with meloxicam treatment after cirrhotic liver resection

AIM:To investigate the effect of meloxicam on the gut-liver axis after cirrhotic liver resection.METHODS:Forty-four male Wistar rats were assigned to three groups:(1)control group(CG);(2)bile duct ligation with meloxicam treatment(BDL+M);and(3)bile duct ligation without meloxicam treatment(BDL).Secondary biliary liver cirrhosis was induced via ligatureof the bile duct in the BDL+M and BDL groups.After 2wk,the animals underwent a 50%hepatectomy.In the BDL+M group 15 min prior to the hepatectomy,one single dose of meloxicam was administered.Parameters measured included:microcirculation of the liver and small bowel;portal venous flow(PVF);gastrointestinal(GI)transit;alanine aminotransferase(ALT);malondialdehyde;interleukin 6(IL-6),transforming growth factor beta 1(TGF-β1)and hypoxia-inducible factor 1 alpha(HIF-1α)levels;mRNA expression of cyclooxigenase-2(COX-2),IL-6 and TGF-β1;liver and small bowel histology;immunohistochemical evaluation of hepatocyte and enterocyte proliferation with Ki-67 and COX-2 liver expression.RESULTS:Proliferative activity of hepatocytes after liver resection,liver flow and PVF were significantly higher in CG vs BDL+M and CG vs BDL group(P<0.05),whereas one single dose of meloxicam ameliorated liver flow and proliferative activity of hepatocytes in BDL+M vs BDL group.COX-2 liver expression at 24h observation time(OT),IL-6 concentration and mRNA IL-6 expression in the liver especially at 3 h OT,were significantly higher in BDL group when compared with the BDL+M and CG groups(P<0.01,P<0.001,P<0.01,respectively).Liver and small bowel histology,according to a semi quantitative scoring system,showed better integrity in BDL+M and CG as compared to BDL group.ALT release and HIF-1αlevels at 1 h OT were significantly higher in BDL+M compared to CG and BDL group(P<0.001 and P<0.01,respectively).Moreover,ALT release levels at 3 and 24 h OT were significantly higher in BDL group compared to CG,P<0.01.GI transit,enterocyte proliferative activity and number of goblet cells were in favor of meloxicam treatment vs BDL group(P<0.05,P<0.001,P<0.01,respectively).Additionally,villus length were higher in BDL+M as compared to BDL group.CONCLUSION:One single dose of meloxicam admin-istered after cirrhotic liver resection was able to cause better function and integrity of the remaining liver and small bowel.

Importance of the gut microbiota in the gut-liver axis in normal and liver disease

The gut microbiota is of growing interest to clinicians and researchers.This is because there is a growing understanding that the gut microbiota performs many different functions,including involvement in metabolic and immune processes that are systemic in nature.The liver,with its important role in detoxifying and metabolizing products from the gut,is at the forefront of interactions with the gut microbiota.Many details of these interactions are not yet known to clinicians and researchers,but there is growing evidence that normal gut microbiota function is important for liver health.At the same time,factors affecting the gut microbiota,including nutrition or medications,may also have an effect through the gut-liver axis.

The immunoregulatory role of fish specific type Ⅱ SOCS via inhibiting metaflammation in the gut-liver axis

SOCS8,also known as CISHb,is a fish-specific type Ⅱ SOCS.Because CISH binds to cytokine receptors and may inhibit STAT5 activation(a substrate of the insulin receptor),SOCS8 may be involved in the control of metaflammation.The socs8-/-zebrafish were created,and both longer trunks and intestinal villi were observed in 1-month-old(mo)fish.Altered mucosal immunity and gut-liver metabolism were also found in socs8-/-fish.Increased intestinal neutrophils and macrophages,together with overexpression of cytokines and T cell markers in this mutant fish,suggested SOCS8's immunoregulating role.During modeling of soybean-induced enteritis using the 3 mo zebrafish,lower expression levels of inflammatory genes but more mucosa barrier disruption were discovered in socs8-/-zebrafish,compared with wide type counterparts.Furthermore,the shrunk villi at 6 mo in socs8-/-fish suggested that the mucosa might have been protected by SOCS8.This is also consistent with the assertion that metaflammation eventually leads to tissue degeneration and premature death.The fact that socs8-/-fish had more hepatic oil droplets compared to their wild-type counterparts suggested SOCS8's role in inhibiting hepatic metaflammation.Transcriptomic analysis as well as 16S rRNA gene sequencing were done on 3 mo socs8-/-fish to methodically reveal the altered immunity and metabolic reprogramming in the gut and liver caused by socs8-/-.The enriched GO terms for the intestinal tract,such as"cytokine-mediated signaling pathway"and"response to external biotic stimulus",as well as KEGG pathways in both gut and liver like"carbon metabolism"and"glycolysis/gluconeogenesis",were consistent with previously revealed pathological clues and improved growth performance at early age,respectively.In addition,the microbiota in the socs8-/-strain had adapted to the host's increased carbohydrate metabolism,as evidenced by higher levels of Bacteroidota.Furthermore,Verrucomicrobiota associated with immunoregulation were found in lower abundance in socs8-/-fish.As a result,current findings indicate that SOCS8 plays immunoregulatory and mucosa-protective roles in the fish gut and liver by inhibiting carbohydrate metabolism.

Role of gut microbiota in the pathogenesis and therapeutics of minimal hepatic encephalopathy via the gut-liver-brain axis

Minimal hepatic encephalopathy(MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety;however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.

Role of gut microbiota via the gut-liver-brain axis in digestive diseases

The gut-brain axis is a bidirectional information interaction system between the central nervous system(CNS) and the gastrointestinal tract, in which gut microbiota plays a key role. The gut microbiota forms a complex network with the enteric nervous system, the autonomic nervous system, and the neuroendocrine and neuroimmunity of the CNS, which is called the microbiota-gut-brain axis. Due to the close anatomical and functional interaction of the gut-liver axis, the microbiota-gut-liver-brain axis has attracted increased attention in recent years. The microbiota-gut-liver-brain axis mediates the occurrence and development of many diseases, and it offers a direction for the research of disease treatment. In this review, we mainly discuss the role of the gut microbiota in the irritable bowel syndrome, inflammatory bowel disease, functional dyspepsia, non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis and hepatic encephalopathy via the gut-liver-brain axis, and the focus is to clarify the potential mechanisms and treatment of digestive diseases based on the further understanding of the microbiota-gut-liver-brain axis.

The key role of gut-liver axis in pyrrolizidine alkaloid-induced hepatotoxicity and enterotoxicity

Pyrrolizidine alkaloids(PAs) are the most common phytotoxins with documented human hepatotoxicity.PAs require metabolic activation by cytochromes P450 to generate toxic intermediates which bind to proteins and form protein adducts,thereby causing cytotoxicity.This study investigated the role of the gut-liver axis in PA intoxication and the underlying mechanisms.We exposed mice to retrorsine(RTS),a representative PA,and for the first time found RTS-induced intestinal epithelium damage and disruption to intestinal barrier function.Using mice with tissue-selective ablation of P450 activity,we found that hepatic P450 s,but not intestinal P450 s,were essential for PA bioactivation.Besides,in RTS-exposed,bile duct-cannulated rats,we found the liver-derived reactive PA metabolites were transported by bile into the intestine to exert enterotoxicity.The impact of gut-derived pathogenic factors in RTS-induced hepatotoxicity was further studied in mice with dextran sulfate sodium(DSS)-induced chronic colitis.DSS treatment increased the hepatic endotoxin level and depleted hepatic reduced glutathione,thereby suppressing the PA detoxification pathway.Compared to RTS-exposed normal mice,the colitic mice displayed more severe RTS-induced hepatic vasculature damage,fibrosis,and steatosis.Overall,our findings provide the first mode-of-action evidence of PA-induced enterotoxicity and highlight the importance of gut barrier function in PA-induced liver injury.

Mesenteric lymph system constitutes the second route in gut-liver axis and transports metabolism-modulating gut microbial metabolites

The gut-liver axis denotes the intricate connection and interaction between gut microbiome and liver, in which compositional and functional shifts in gut microbiome affect host metabolism. Hepatic portal vein of the blood circulation system has been thought to be the major route for metabolite transportation in the gut-liver axis, but the existence and importance of other routes remain elusive. Here, we perform metabolome comparison in blood circulation and mesenteric lymph systems and identify significantly shifted metabolites in serum and mesentery. Using cellular assays, we find that the majority of decreased metabolites in lymph system under high-fat diet are effective in alleviating metabolic disorders, indicating a high potential of lymph system in regulating liver metabolism. Among those, a representative metabolite, L-carnitine, reduces diet-induced obesity in mice. Metabolic tracing analysis identifies that L-carnitine is independently transported by the mesenteric lymph system, serving as an example that lymph circulation comprises a second route in the gut-liver axis to modulate liver metabolism. Our study provides new insights into metabolite transportation via mesenteric lymph system in the gut-liver axis, offers an extended scope for the investigations in host-gut microbiota metabolic interactions and potentially new targets in the treatment of metabolic disorders.

Immune regulation of the gut-brain axis and lung-brain axis involved in ischemic stroke

Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks.Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability.In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other.Here,we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis.We found that abnormal intestinal flora,the intestinal microenvironment,lung infection,chronic diseases,and mechanical ventilation can worsen the outcome of ischemic stroke.This review also introduces the influence of the brain on the gut and lungs after stroke,highlighting the bidirectional feedback effect among the gut,lungs,and brain.

Sphingosine-1-phosphate signaling and the gut-liver axis in liver diseases

The liver is the central organ involved in lipid metabolism and the gastrointestinal(GI)tract is responsible for nutrient absorption and partitioning.Obesity,dyslipidemia and metabolic disorders are of increasing public health concern worldwide,and novel therapeutics that target both the liver and the GI tract(gut-liver axis)are much needed.In addition to aiding fat digestion,bile acids act as important signaling molecules that regulate lipid,glucose and energy metabolism via activating nuclear receptor,G protein-coupled receptors(GPCRs),Takeda G protein receptor 5(TGR5)and sphingosine-1-phosphate receptor 2(S1PR2).Sphingosine-1-phosphate(S1P)is synthesized by two sphingosine kinase isoforms and is a potent signaling molecule that plays a critical role in various diseases such as fatty liver,in-flammatory bowel disease(IBD)and colorectal cancer.In this review,we will focus on recent findings related to the role of S1P-mediated signaling pathways in the gut-liver axis.

In situ calibrated angle between the quantization axis and the propagating direction of the light field for trapping neutral atoms

The recently developed magic-intensity trapping technique of neutral atoms efficiently mitigates the detrimental effect of light shifts on atomic qubits and substantially enhances the coherence time. This technique relies on applying a bias magnetic field precisely parallel to the wave vector of a circularly polarized trapping laser field. However, due to the presence of the vector light shift experienced by the trapped atoms, it is challenging to precisely define a parallel magnetic field, especially at a low bias magnetic field strength, for the magic-intensity trapping of85Rb qubits. In this work, we present a method to calibrate the angle between the bias magnetic field and the trapping laser field with the compensating magnetic fields in the other two directions orthogonal to the bias magnetic field direction. Experimentally, with a constantdepth trap and a fixed bias magnetic field, we measure the respective resonant frequencies of the atomic qubits in a linearly polarized trap and a circularly polarized one via the conventional microwave Rabi spectra with different compensating magnetic fields and obtain the corresponding total magnetic fields via the respective resonant frequencies using the Breit–Rabi formula. With known total magnetic fields, the angle is a function of the other two compensating magnetic fields.Finally, the projection value of the angle on either of the directions orthogonal to the bias magnetic field direction can be reduced to 0(4)° by applying specific compensating magnetic fields. The measurement error is mainly attributed to the fluctuation of atomic temperature. Moreover, it also demonstrates that, even for a small angle, the effect is strong enough to cause large decoherence of Rabi oscillation in a magic-intensity trap. Although the compensation method demonstrated here is explored for the magic-intensity trapping technique, it can be applied to a variety of similar precision measurements with trapped neutral atoms.

Unraveling the gut-brain axis:the impact of steroid hormones and nutrition on Parkinson's disease

This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.Progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurodegenerative diseases such as Parkinson's disease.

Irisin/BDNF signaling in the muscle-brain axis and circadian system: A review

In mammals,the timing of physiological,biochemical and behavioral processes over a 24-h period is controlled by circadian rhythms.To entrain the master clock located in the suprachiasmatic nucleus of the hypothalamus to a precise 24-h rhythm,environmental zeitgebers are used by the circadian system.This is done primarily by signals from the retina via the retinohypothalamic tract,but other cues like exercise,feeding,temperature,anxiety,and social events have also been shown to act as non-photic zeitgebers.The recently identified myokine irisin is proposed to serve as an entraining non-photic signal of exercise.Irisin is a product of cleavage and modification from its precursor membrane fibronectin typeⅢdomain-containing protein 5(FNDC5)in response to exercise.Apart from well-known peripheral effects,such as inducing the"browning"of white adipocytes,irisin can penetrate the blood-brain barrier and display the effects on the brain.Experimental data suggest that FNDC5/irisin mediates the positive effects of physical activity on brain functions.In several brain areas,irisin induces the production of brain-derived neurotrophic factor(BDNF).In the master clock,a significant role in gating photic stimuli in the retinohypothalamic synapse for BDNF is suggested.However,the brain receptor for irisin remains unknown.In the current review,the interactions of physical activity and the irisin/BDNF axis with the circadian system are reconceptualized.