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.

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.

Insights of gut-liver axis in hepatic diseases:Mechanisms,clinical implications,and therapeutic potentials

With the rising prevalence of chronic liver diseases worldwide,there exists a need to diversify our artillery to incorporate a plethora of diagnostic and therapeutic methods to combat this disease.Currently,the most common causes of liver disease are non-alcoholic fatty liver disease,hepatitis,and alcoholic liver disease.Some of these chronic diseases have the potential to transform into hepatocellular carcinoma with advancing fibrosis.In this review,we analyse the relationship between the gut and liver and their significance in liver disease.This two-way relationship has interesting effects on each other in liver diseases.The gut microbiota,through its metabolites,influences the metabolism in numerous ways.Careful manipulation of its composition can lead to the discovery of numerous therapeutic potentials that can be applied in the treatment of various liver diseases.Numerous cohort studies with a pan-omics approach are required to understand the association between the gut microbiome and hepatic disease progression through which we can identify effective ways to deal with this issue.

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, insulin-resistance, 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.

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.

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.

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.

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.

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.

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.

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.

Impact of microplastics and nanoplastics on liver health:Current understanding and future research directions

With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.

基于肠-肝轴探讨清肝降脂方对代谢相关脂肪性肝病大鼠肠道屏障的作用研究

目的基于肠-肝轴理论探讨清肝降脂方对高脂饲料诱导的代谢相关脂肪性肝病(MAFLD)大鼠肠道屏障的作用。方法60只SPF级雄性SD大鼠,随机抽取10只作为正常组,余下作为高脂饮食组,给予高脂饲料喂养8周。造模成功后,将高脂饮食组大鼠随机分为模型组和中药低剂量组、中剂量组、高剂量组及水林佳组。观察各组大鼠肝脏及回肠末端组织病理变化、血清生化学及血清内毒素水平,回肠组织中紧密连接蛋白ZO-1、Occludin表达情况。结果与正常组比较,模型组大鼠肝脏和回肠组织可见明显病理损伤,血清ALT、TC、TG、LDL-C及血清LPS水平表达量均明显增高,均具有统计学意义(P<0.05),回肠组织中ZO-1、Occludin蛋白阳性表达降低(P<0.05)。与模型组比较,水林佳组和中药高、中剂量均能明显降低ALT、TC、TG水平,降低LDL-C含量(P<0.05)。水林佳及中药组大鼠血清LPS水平均明显低于模型组(P<0.05),水林佳组以及中药高、中剂量组ZO-1、Occludin蛋白阳性表达增多,中药低剂量组蛋白表达略增加。结论清肝降脂方可以调节大鼠脂质代谢,修复肠道紧密连接,维持正常肠道黏膜屏障功能,阻止肠内炎性因子、内毒素等进入肝脏,提示清肝降脂方治疗MAFLD作用机制可能与调节肠-肝轴、改善肠道免疫屏障有关。

基于16S rDNA序列分析胃肠外营养相关性胆汁淤积症早产儿肠道微生态和肠-肝轴的研究

目的旨在研究胃肠外营养相关性胆汁淤积症(PNAC)早产儿的肠道微生态特征和肠-肝轴在PNAC发病中的作用。方法采用前瞻性研究收集2020年5月1日至2022年12月31日在中山市人民医院新生儿监护室收治的早产儿,住院期间曾接收14d以上的胃肠外营养治疗。实验组为13例患有PNAC的早产儿,对照组为24例未患PNAC的早产儿。对两组患儿不同日龄的粪便中肠道菌群的DNA情况采用16S rDNA序列分析技术进行测定。同时检测两组早产儿不同日龄血清血炎症细胞因子包括降钙素原(PCT)、白细胞介素6(IL-6)水平和肝胆生化变化,通过统计学分析组间差异。结果实验组与对照组生后第1、7和14d的肠道菌门构成比的差异无统计学意义(χ_(D1)^(2)=0,χ_(D7)^(2)=1.06,χ_(D14)^(2)=6.98,P均>0.05),生后第30d的肠道菌门构成比的差异有统计学意义(χ_(D30)^(2)=16.29,P<0.05);对比两组出生后不同日龄肠道菌门的相对丰度,结果显示两组在生后第7d厚壁菌门、拟杆菌门和变形菌门相对丰度的差异无统计学意义(t值分别为0.69、2.00、2.00,P均>0.05);两组在生后第14d厚壁菌门、拟杆菌门、变形菌门相对丰度的差异均有统计学意义(t值分别为15.41、24.74、6.64,P均<0.05),两组在生后第30d厚壁菌门、拟杆菌门、变形菌门和放线菌门相对丰度的差异有统计学意义(t值分别为37.88、25.88、34.63、33.36,P均<0.05),提示在生后第14d和第30d实验组厚壁菌门相对丰度低于对照组,实验组拟杆菌门、变形菌门的相对丰度均高于对照组。对比两组动态的肝胆生化和炎症指标,结果显示,血清谷丙转氨酶(ALT)、总胆红素(T-BIL)、直接胆红素(D-BIL)、总胆汁酸(TBA)、γ-谷氨酰转肽酶(γ-GT)水平上,实验组在生后第14d、第30d和第60d血清ALT、T-BIL、D-BIL、TBA、γ-GT水平高于对照组,通过统计学分析,我们发现组间差异具有统计学意义(P均<0.05);实验组血清PCT、IL-6水平在生后第14d和第30d高于对照组,组与组之间差异具有统计学意义(PCT:t_(D14)=16.39,t_(D30)=25.29,IL-6:t_(D14)=7.03,t_(D30)=9.65,P均<0.05)。实验组肠外营养(PN)的持续时间(22.0±3.2d)长于对照组(17.8±3.1d),两组PN的持续时间的差异有统计学意义(t=3.841,P<0.001)。结论患有PNAC且胃肠外营养超过14d的新生儿其在出生14d后的肠道菌群的组成与无合并PNAC的新生儿存在差异。患有PNAC新生儿在胃肠外营养至生后第14d和第30d时肠道菌群以拟杆菌门和变形菌门为主,且伴血炎症指标增高和胆汁淤积加重。PN持续时间长、肠道菌群的变化和炎症指标的增高可能与PNAC病情的发生发展有关,具体的机制仍需进一步深入研究。

微生物-肠-肝轴与酒精性肝病及其营养干预研究进展

酒精性肝病(alcoholic liver disease,ALD)是全球最普遍的慢性肝病类型,早期表现为脂肪肝,进而演变成脂肪性肝炎,随着饮酒时间延长会发展成肝纤维化和肝硬化。肠-肝轴是指肠道及其微生物群与肝脏之间的双向作用,由门静脉和胆道建立。酒精会破坏这一双向作用,导致肠道微生物群紊乱和病原体易位到肝脏,造成肝损伤。本文以肠道屏障、肠道微生物组成、肠道微生物成分和肠道微生物代谢产物为主,综述了肠-肝轴介导ALD发生发展的作用机制以及ALD的营养干预措施,尤其是靶向噬菌体干预肠道微生物群以及三甲胺、溶细胞素、念珠菌溶素在ALD中的作用,以期为以肠-肝轴为靶点抗ALD功能物质的发现、营养干预和功能性食品的开发提供基础。