The gut-eye axis:from brain neurodegenerative diseases to age-related macular degeneration

Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are consequently lacking.The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host.The intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other factors.Such dysregulation of the intestinal flora can disrupt the microecological balance,resulting in immunological and metabolic dysfunction in the host,and affecting the development of many diseases.In recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the brain.Indeed,several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.Similarly,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular disorders.Moreover,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies.As such,the intestinal flora may play an important role in age-related macular degeneration.Given the above context,the present review aims to clarify the gut-brain and gut-eye connections,assess the effect of intestinal flora and metabolites on age-related macular degeneration,and identify potential diagnostic markers and therapeutic strategies.Currently,direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited,while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular degeneration.Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms.

Predicting short-term major postoperative complications in intestinal resection for Crohn’s disease:A machine learning-based study

BACKGROUND Due to the complexity and numerous comorbidities associated with Crohn’s disease(CD),the incidence of postoperative complications is high,significantly impacting the recovery and prognosis of patients.Consequently,additional stu-dies are required to precisely predict short-term major complications following intestinal resection(IR),aiding surgical decision-making and optimizing patient care.AIM To construct novel models based on machine learning(ML)to predict short-term major postoperative complications in patients with CD following IR.METHODS A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022.The study participants were randomly allocated to either a training cohort or a validation cohort.The logistic regression and random forest(RF)were applied to construct models in the training cohort,with model discrimination evaluated using the area under the curves(AUC).The validation cohort assessed the performance of the constructed models.RESULTS Out of the 259 patients encompassed in the study,5.0%encountered major postoperative complications(Clavien-Dindo≥III)within 30 d following IR for CD.The AUC for the logistic model was 0.916,significantly lower than the AUC of 0.965 for the RF model.The logistic model incorporated a preoperative CD activity index(CDAI)of≥220,a diminished preoperative serum albumin level,conversion to laparotomy surgery,and an extended operation time.A nomogram for the logistic model was plotted.Except for the surgical approach,the other three variables ranked among the top four important variables in the novel ML model.CONCLUSION Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complic-ations in patients with CD,with the RF model showing more superiority.A preoperative CDAI of≥220,a di-minished preoperative serum albumin level,and an extended operation time might be the most crucial variables.The findings of this study can assist clinicians in identifying patients at a higher risk for complications and offering personalized perioperative management to enhance patient outcomes.

Differential diagnosis of Crohn’s disease and intestinal tuberculosis based on ATR-FTIR spectroscopy combined with machine learning

BACKGROUND Crohn’s disease(CD)is often misdiagnosed as intestinal tuberculosis(ITB).However,the treatment and prognosis of these two diseases are dramatically different.Therefore,it is important to develop a method to identify CD and ITB with high accuracy,specificity,and speed.AIM To develop a method to identify CD and ITB with high accuracy,specificity,and speed.METHODS A total of 72 paraffin wax-embedded tissue sections were pathologically and clinically diagnosed as CD or ITB.Paraffin wax-embedded tissue sections were attached to a metal coating and measured using attenuated total reflectance fourier transform infrared spectroscopy at mid-infrared wavelengths combined with XGBoost for differential diagnosis.RESULTS The results showed that the paraffin wax-embedded specimens of CD and ITB were significantly different in their spectral signals at 1074 cm^(-1) and 1234 cm^(-1) bands,and the differential diagnosis model based on spectral characteristics combined with machine learning showed accuracy,specificity,and sensitivity of 91.84%,92.59%,and 90.90%,respectively,for the differential diagnosis of CD and ITB.CONCLUSION Information on the mid-infrared region can reveal the different histological components of CD and ITB at the molecular level,and spectral analysis combined with machine learning to establish a diagnostic model is expected to become a new method for the differential diagnosis of CD and ITB.

Computed tomography-based radiomics combined with machine learning allows differentiation between primary intestinal lymphoma and Crohn's disease

BACKGROUND Due to similar clinical manifestations and imaging signs,differential diagnosis of primary intestinal lymphoma(PIL)and Crohn's disease(CD)is a challenge in clinical practice.AIM To investigate the ability of radiomics combined with machine learning methods to differentiate PIL from CD.METHODS We collected contrast-enhanced computed tomography(CECT)and clinical data from 120 patients form center 1.A total of 944 features were extracted singlephase images of CECT scans.Using the last absolute shrinkage and selection operator model,the best predictive radiographic features and clinical indications were screened.Data from 54 patients were collected at center 2 as an external validation set to verify the robustness of the model.The area under the receiver operating characteristic curve,accuracy,sensitivity and specificity were used for evaluation.RESULTS A total of five machine learning models were built to distinguish PIL from CD.Based on the results from the test group,most models performed well with a large area under the curve(AUC)(>0.850)and high accuracy(>0.900).The combined clinical and radiomics model(AUC=1.000,accuracy=1.000)was the best model among all models.CONCLUSION Based on machine learning,a model combining clinical data with radiologic features was constructed that can effectively differentiate PIL from CD.

Advances in the research of intestinal fungi in Crohn's disease

This article reviews of the original research published by Wu et al in the World Journal of Gastroenterology,delving into the pivotal role of the gut microbiota in the pathogenesis of Crohn's disease(CD).Insights were gained from fecal microbiota transplantation(FMT)in mouse models,revealing the intricate interplay between the gut microbiota,mesenteric adipose tissue(MAT),and creeping fat.The study uncovered the characteristics of inflammation and fibrosis in the MAT and intestinal tissues of patients with CD;moreover,through the FMT mouse model,it observed the impact of samples from healthy patients and those with CD on symptoms.The pathogenesis of CD is complex,and its etiology remains unclear;however,it is widely believed that gut microbiota dysbiosis plays a significant role.Recently,with the development and application of next-generation sequen-cing technology,research on the role of fungi in the pathogenesis and chronicity of CD has deepened.This editorial serves as a supplement to the research by Wu et al who discussed advances related to the study of fungi in CD.

Intestinal Behçet's disease: A review of clinical diagnosis and treatment

Behçet's disease(BD)is a chronic inflammatory disorder prone to frequent re-currences,with a high predilection for intestinal involvement.However,the ef-ficacy and long-term effects of surgical treatment for intestinal BD are unknown.In the current issue of World J Gastrointest Surg,Park et al conducted a retrospec-tive analysis of 31 patients with intestinal BD who received surgical treatment.They found that elevated C-reactive protein levels and emergency surgery were poor prognostic factors for postoperative recurrence,emphasizing the adverse impact of severe inflammation on the prognosis of patients with intestinal BD.This work has clinical significance for evaluating the postoperative condition of intestinal BD.The editorial attempts to summarize the clinical diagnosis and treatment of intestinal BD,focusing on the impact of adverse factors on surgical outcomes.We hope this review will facilitate more precise postoperative management of patients with intestinal BD by clinicians.

Influencing factors and preventive measures of infectious complications after intestinal resection for Crohn’s disease

The incidence of Crohn’s disease(CD)has increased in recent years,with most patients requiring intestinal resection.Complications after intestinal resection for CD can lead to poor prognosis and recurrence,among which infectious complic-ations are the most common.This study aimed to investigate the common risk factors,including medications,preoperative nutritional status,surgery-related factors,microorganisms,lesion location and type,and so forth,causing infectious complications after intestinal resection for CD,and to propose corresponding preventive measures.The findings provided guidance for identifying suscept-ibility factors and the early intervention and prevention of infectious complic-ations after intestinal resection for CD in clinical practice.

Machine learning as a tool predicting short-term postoperative complications in Crohn’s disease patients undergoing intestinal resection: What frontiers?

The recent study,“Predicting short-term major postoperative complications in intestinal resection for Crohn’s disease:A machine learning-based study”invest-igated the predictive efficacy of a machine learning model for major postoperative complications within 30 days of surgery in Crohn’s disease(CD)patients.Em-ploying a random forest analysis and Shapley Additive Explanations,the study prioritizes factors such as preoperative nutritional status,operative time,and CD activity index.Despite the retrospective design’s limitations,the model’s robu-stness,with area under the curve values surpassing 0.8,highlights its clinical potential.The findings align with literature supporting preoperative nutritional therapy in inflammatory bowel diseases,emphasizing the importance of compre-hensive assessment and optimization.While a significant advancement,further research is crucial for refining preoperative strategies in CD patients.

Dajianzhong decoction:a review of its phytochemistry and therapeutic potential for gastrointestinal disease

Dajianzhong decoction(DJZD)is one of the traditional herbal prescriptions originated from Synopsis of Golden Chamber,which clinically used for the treatment of various gastrointestinal(GI)disease.This paper was aimed to provide a systematic review on the phytochemistry of DJZD and its therapeutic potential for GI disease and the mechanism.Finally,the possible development and perspectives for future research on this prescription were also discussed.To date,over 60 compounds have been identified form DJZD,including unsaturated fatty acid,saponins,and polyphenols,with hydroxy-sanshool and ginsenoside compounds as the predominant ones.DJZD possessed widely pharmacological activities on the GI disease from the Eastern Han Dynasty to the present,such as intestinal obstruction,colitis,and irritable bowel syndrome.Especially for the intestinal obstruction,it had demonstrated the efficacy of DJZD treatment for relief of postoperative ileus in patients undergoing surgery for GI cancer.The detailed mechanism was mainly related with NF-ᴋB signaling pathway.However,further research elucidating the protective effects of DJZD on GI disease,exploring new clinical effects,as well as establishing criteria for quality control for DJZD should be studied.

Transabdominal intestinal ultrasound and its parameters used in the assessment of pediatric inflammatory bowel disease

This article extends on the use of transabdominal intestinal ultrasound in diagnosing pediatric inflammatory bowel disease.Some of the more essential features used in assessing bowel inflammation,such as hyperemia and wall thickness on ultrasound,are expanded upon from the publication on imaging and endoscopic tools in pediatric inflammatory bowel disease.

Different roles of capsule endoscopy and double-balloon enteroscopy in obscure small intestinal diseases

AIM: To compare the roles of capsule endoscopy(CE)and double-balloon enteroscopy(DBE) in the diagnosis of obscure small bowel diseases.METHODS: From June 2009 to December 2014, 88 patients were included in this study; the patients had undergone gastroscopy, colonoscopy, radiological small intestinal barium meal, abdominal computed tomography or magnetic resonance imaging scan and mesenteric angiography, but their diagnoses were still unclear. The patients with gastrointestinal obstructions,fistulas, strictures, or cardiac pacemakers, as well as pregnant women, and individuals who could not accept the capsule-retention or capsule-removal surgery were excluded. Patients with heart, lung and other vital organ failure diseases were also excluded. Everyone involved in this study had undergone CE and DBE. The results were divided into:(1) the definite diagnosis(the diagnosis was confirmed at least by one of the biopsy,surgery, pathology or the drug treatment effects with follow-up for at least 3 mo);(2) the possible diagnosis(a possible diagnosis was suggested by CE or DBE,but not confirmed by the biopsy, surgery or follow-up drug treatment effects); and(3) the unclear diagnosis(no exact causes were provided by CE and DBE for the disease). The detection rate and the diagnostic yield of the two methods were compared. The differencein the etiologies between CE and DBE was estimated,and the different possible etiologies caused by the age groups were also investigated.RESULTS: CE exhibited a better trend than DBE for diagnosing scattered small ulcers(P = 0.242, Fisher's test), and small vascular malformations(χ 2 = 1.810,P = 0.179, Pearson χ 2 test), but with no significant differences, possible due to few cases. However,DBE was better than CE for larger tumors(P =0.018, Fisher's test) and for diverticular lesions with bleeding ulcers(P = 0.005, Fisher's test). All three hemangioma cases diagnosed by DBE in this study(including sponge hemangioma, venous hemangioma,and hemangioma with hamartoma lesions) were all confirmed by biopsy. Two parasite cases were found by CE, but were negative by DBE. This study revealed no obvious differences in the detection rates(DR) of CE(60.0%, 53/88) and DBE(59.1%, 52/88). However,the etiological diagnostic yield(DY) difference was apparent. The CE diagnostic yield was 42.0%(37/88),and the DBE diagnostic yield was 51.1%(45/88).Furthermore, there were differences among the age groups(χ 2 = 22.146, P = 0.008, Kruskal Wallis Test). Small intestinal cancer(5/6 cases), vascular malformations(22/29 cases), and active bleeding(3/4cases) appeared more commonly in the patients over50 years old, but diverticula with bleeding ulcers were usually found in the 15-25-year group(4/7cases). The over-25-year group accounted for the stromal tumors(10/12 cases).CONCLUSION: CE and DBE each have their own advantages and disadvantages. The appropriate choice depends on the patient's age, tolerance, and clinical manifestations. Sometimes CE followed by DBE is necessary.

Bile acid signaling through farnesoid X and TGR5 receptors in hepatobiliary and intestinal diseases

BACKGROUND： The well-known functions of bile acids（BAs） are the emulsification and absorption of lipophilic xenobiotics. However, the emerging evidences in the past decade showed that BAs act as signaling molecules that not only autoregulate their own metabolism and enterohepatic recirculation, but also as important regulators of integrative metabolism by activating nuclear and membrane-bound G protein-coupled receptors. The present review was to get insight into the role of maintenance of BA homeostasis and BA signaling pathways in development and management of hepatobiliary and intestinal diseases.DATA SOURCES： Detailed and comprehensive search of PubM ed and Scopus databases was carried out for original and review articles.RESULTS： Disturbances in BA homeostasis contribute to the development of several hepatobiliary and intestinal disorders, such as non-alcoholic fatty liver disease, liver cirrhosis, cholesterol gallstone disease, intestinal diseases and both hepatocellular and colorectal carcinoma.CONCLUSION： Further efforts made in order to advance the understanding of sophisticated BA signaling network may be promising in developing novel therapeutic strategies related not only to hepatobiliary and gastrointestinal but also systemic diseases.

Gastrointestinal motility and absorptive disorders in patients with inflammatory bowel diseases: Prevalence, diagnosis and treatment

Inflammatory bowel diseases(IBD),Crohns disease and ulcerative colitis,are chronic conditions associated with high morbidity and healthcare costs.The natural history of IBD is variable and marked by alternating periods of flare and remission.Even though the use of newer therapeutic targets has been associated with higher rates of mucosal healing,a great proportion of IBD patients remain symptomatic despite effective control of inflammation.These symptoms may include but not limited to abdominal pain,dyspepsia,diarrhea,urgency,fecal incontinence,constipation or bloating.In this setting,commonly there is an overlap with gastrointestinal(GI)motility and absorptive disorders.Early recognition of these conditions greatly improves patient care and may decrease the risk of mistreatment.Therefore,in this review we describe the prevalence,diagnosis and treatment of GI motility and absorptive disorders that commonly affect patients with IBD.

Intestinal epithelial cells in inflammatory bowel diseases

The pathogenesis of inflammatory bowel diseases (IBDs) seems to involve a primary defect in one or more of the elements responsible for the maintenance of intestinal homeostasis and oral tolerance. The most important element is represented by the intestinal barrier, a complex system formed mostly by intestinal epithelial cells (IECs). IECs have an active role in producing mucus and regulating its composition; they provide a physical barrier capable of controlling antigen traff ic through the intestinal mucosa. At the same time, they are able to play the role of non-professional antigen presenting cells, by processing and presenting antigens directly to the cells of the intestinal immune system. On the other hand, immune cells regulate epithelial growth and differentiation, producing a continuous bi-directional cross-talk within the barrier. Several alterations of the barrier function have been identif ied in IBD, starting from mucus features up to its components, from epithelial junctions up to the Toll-like receptors, and altered immune responses. It remains to be understood whether these defects are primary causes of epithelial damage or secondary effects. We review the possible role of the epithelial barrier and particularly describe the role of IECs in the pathogenesis of IBD.

Intestinal Microecology in Children with Pneumonia: The Relationship Between Digestive Health and Disease Recovery

This paper explores the association between intestinal microecology and digestive health and disease recovery in children with pneumonia.Intestinal microecological imbalance is common in children with pneumonia,which is closely associated with digestive health and disease recovery.Intestinal microecological imbalance may affect digestive enzyme activity,intestinal mucosal barrier function,and nutrient absorption,which in turn affects digestive health.In addition,intestinal microecological imbalances may be associated with immune regulation,inflammatory responses,and pathogen suppression,affecting disease recovery.Strategies to regulate intestinal microecology include probiotic supplementation,dietary modification,and pharmacological treatment.Currently,the study of intestinal microecology in children with pneumonia faces challenges,and there is a need for improved research methods,individualized treatment strategies,and the development of novel probiotics.In conclusion,the intestinal microecology of children with pneumonia is closely related to digestive health and disease recovery,and the regulation of intestinal microecology is of great significance to the treatment of children with pneumonia.Furthermore,future research should further explore the application of the microecology of the intestinal microecology in the treatment of children with pneumonia.

Progress in elucidating the relationship between Helicobacter pylori infection and intestinal diseases

Helicobacter pylori(H.pylori)infection causes changes to the intestinal flora,such as small intestinal bacterial overgrowth,and increases gastric acid secretionstimulating gastrointestinal hormones,mainly gastrin,due to a decrease in gastric acid caused by atrophic gastritis.In addition,the cellular components of H.pylori travel through the intestinal tract,so the bacterial infection affects the immune system.Therefore,the effects of H.pylori infection are observed not only in the stomach and the proximal duodenum but also in the small and large intestines.In particular,meta-analyses reported that H.pylori-infected individuals had an increased risk of colorectal adenoma and colorectal cancer.Moreover,a recent study reported that the risk of developing colorectal cancer was increased in subjects carrying H.pylori vacuolating cytotoxin A antibody.In addition,it has been reported that H.pylori infection exacerbates the symptoms of Fabry’s disease and familial Mediterranean fever attack and is involved in irritable bowel syndrome and small intestinal ulcers.On the other hand,some studies have reported that the frequency of ulcerative colitis,Crohn’s disease,and celiac disease is low in H.pylori-infected individuals.Thus,H.pylori infection is considered to have various effects on the small and large intestines.However,few studies have reported on these issues,and the details of their effects have not been well elucidated.Therefore,additional studies are needed.

Effects of a high fat diet on intestinal microbiota and gastrointestinal diseases

Along with the rapid development of society, lifestyles and diets have gradually changed. Due to overwhelming material abundance, high fat, high sugar and high protein diets are common. Numerous studies have determined that diet and its impact on gut microbiota are closely related to obesity and metabolic diseases. Different dietary components affect gut microbiota, thus impacting gastrointestinal disease occurrence and development. A large number of related studies are progressing rapidly. Gut microbiota may be an important intermediate link, causing gastrointestinal diseases under the influence of changes in diet and genetic predisposition. To promote healthy gut microbiota and to prevent and cure gastrointestinal diseases, diets should be improved and supplemented with probiotics.

Capsule endoscopy in non-steroidal anti-inflammatory drugs-enteropathy and miscellaneous,rare intestinal diseases

Despite significant advances over the last decade, mucosal lesions of the small bowel are poorly detected by imaging studies such as CT scan, MRI-enteroclysis and contrast-enhanced abdominal ultrasound. Capsule endoscopy (CE) has dramatically changed the diagnostic approach to intestinal diseases. Moreover, the use of CE can be extended to include other conditions. However, it is diffi cult to assess the positive influence of CE on patient outcomes in conditions involving a small number of patients, or in critically ill and diff icult to examine patients. CE has the advantage of diagnosing intestinal lesions and of directing the use of double balloon enteroscopy (DBE) in order to obtain biopsy specimens. Moreover, CE allows repeated assessment in chronic conditions, especially to detect relapse of an infectious disease.

Increased intestinal permeability in inflammatory bowel diseases assessed by iohexol test

AIM:To study intestinal permeability(IP) and its relationship to the disease activity in patients with inflammatory bowel diseases(IBD)-Crohn's disease(CD) and ulcerative colitis(UC).METHODS:Fifty-eight patients with active IBD(32 with CD and 26 with UC) and 25 healthy controls consented to participate in the study.The clinical activity of CD was estimated using the Crohn's Disease Activity Index(CDAI),and the endoscopic activity of UC using the Mayo scoring system.IP was assessed by the rise in levels of iohexol,which was administered orally(25 mL,350 mg/mL) 2 h after breakfast.Three and six hours later serum(SIC mg/L) and urine(UIC g/mol) iohexol concentrations were determined by a validated HPLC-UV technique.RESULTS:In the CD group,SIC values at 3 h(2.95 ± 2.11 mg/L) and at 6 h after ingestion(2.63 ± 2.18 mg/L) were significantly higher compared to those of healthy subjects(1.25 ± 1.40 mg/L and 1.11 ± 1.10 mg/L,respectively,P < 0.05).UIC(g/mol) values were also higher in patients,but the differences were significant only for UIC at 6 h.Significant positive correlation(P < 0.05) was found between the CDAI and IP,assessed by SIC at 3 h(r = 0.60) and 6 h(r = 0.74) after the ingestion.In comparison to controls,SIC and UIC of UC patients were higher in the two studied periods,but the differences were significant at 6 h only.Significantly higher values of SIC(P < 0.05) were found in patients with severe endoscopic activity of UC compared to those of patients with mild and moderate activity(3.68 ± 3.18 vs 0.92 ± 0.69 mg/L).CONCLUSION:Serum levels of iohexol at 3 h and 6 h after its ingestion reflect increased IP,which is related to the disease activity in patients with IBD.

Role ofγδT cells in liver diseases and its relationship with intestinal microbiota

γδT cells are unconventional T lymphocytes that bridge innate and adaptive immunity.Based on the composition of T cell receptor and the cytokines produced,γδT cells can be divided into diverse subsets that may be present at different locations,including the liver,epithelial layer of the gut,the dermis and so on.Many of these cells perform specific functions in liver diseases,such as viral hepatitis,autoimmune liver diseases,non-alcoholic fatty liver disease,liver cirrhosis and liver cancers.In this review,we discuss the distribution,subsets,functions ofγδT cells and the relationship between the microbiota andγδT cells in common hepatic diseases.AsγδT cells have been used to cure hematological and solid tumors,we are interested inγδT cell-based immunotherapies to treat liver diseases.