Background: Parenteral nutrition (PN) is essential for patients with intestinal failure (IF) but is associated with complications such as dysbiosis, small intestinal bacterial overgrowth, catheter-related infections, and intestinal failure–associated liver disease (IFALD). Growing evidence indicates that gut microbiota alterations contribute to the pathogenesis of these complications, supporting microbiota-oriented interventions as potential adjunctive therapies. Methods: Data sources: A structured literature search was conducted in PubMed, Web of Science, and Scopus from inception to December 2025.Study eligibility criteria: Clinical trials, observational studies, mechanistic studies, and relevant reviews evaluating gut microbiota features or microbiome-targeted interventions in IF or PN-dependent populations were included.Participants: Pediatric and adult patients with intestinal failure or short bowel syndrome, as well as relevant animal models.Interventions: Microbiota-oriented strategies, including probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT).Statistical analysis: Due to substantial heterogeneity in study design, interventions, and outcomes, meta-analysis was not performed; findings were synthesized qualitatively. Results: PN dependence was consistently associated with reduced microbial diversity, enrichment of Proteobacteria and Lactobacillaceae, and depletion of obligate anaerobes and short-chain fatty acid–producing taxa. Microbiota-oriented interventions demonstrated biological plausibility and microbiome modulation in selected studies; however, clinical benefits were variable and generally modest. Safety concerns, limited microbial engraftment, small sample sizes, and patient heterogeneity limited generalizability. Conclusion: Gut microbiota dysbiosis plays a contributory role in PN-related complications of IF. Microbiota-oriented interventions are promising but remain unproven, underscoring the need for well-designed, stratified clinical studies to define efficacy, safety, and responsive patient subgroups.
Studies on fecal microbiota transplantation (FMT) have reported inconsistent connections between clinical outcomes and donor strain engraftment. Analyses of subspecies-level crosstalk and its influences on lineage transfer in metagenomic FMT datasets have proved challenging, as single-nucleotide polymorphisms (SNPs) are generally not linked and are often absent. Here, we utilized species genome bin (SGB), which employs co-abundance binning, to investigate subspecies-level microbiome dynamics in patients with autism spectrum disorder (ASD) who had gastrointestinal comorbidities and underwent encapsulated FMT (Chinese Clinical Trial: 2100043906). We found that interactions between donor and recipient microbes, which were overwhelmingly phylogenetically divergent, were important for subspecies transfer and positive clinical outcomes. Additionally, a donor-recipient SGB match was indicative of a high likelihood of strain transfer. Importantly, these ecodynamics were shared across FMT datasets encompassing multiple diseases. Collectively, these findings provide detailed insight into specific microbial interactions and dynamics that determine FMT success.
Introduction: Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of advanced cancers. However, the increased use of ICI has also resulted in a higher incidence of ICI-related cardiovascular side effects, including myocarditis, which has a high mortality rate of nearly 50%. Understanding the mechanisms underlying ICI-related cardiotoxicity is essential for identifying new therapeutic targets and improving patient survival. Hypothesis: We hypothesized that ICI-myocarditis has a unique transcriptomic profile that could be used to identify new drug targets. Methods: To test our hypothesis, we isolated RNA from our ICI-myocarditis mouse hearts and performed RNA-seq using the Illumina NovaSeq 6000. We also reanalyzed a human IC-myocarditis dataset downloaded from the Gene Expression Omnibus database. Results: Our results demonstrated that in both our animal models and patients, the upregulated pathways in ICI myocarditis heart tissues were enriched for regulation of T cell activation, leukocyte adhesion, and multiple cytokine signaling pathways. Conversely, downregulated pathways included those involved in cellular respiration, oxidative phosphorylation, and cardiac conduction. The most significantly upregulated genes were involved in innate and adaptive immune responses, including the CD8-dependent gene program and response to interferon-gamma of macrophages. By querying the Drug Gene Interaction Database, we identified several novel biologically plausible therapeutic targets. Correspondingly, a number of FDA-approved drugs were revealed, including monoclonal or chimeric antibodies such as Tocilizumab and Alemtuzumab, recombinant proteins like Abatacept and Anakinra, as well as small molecules such as Ruxolitinib and Imiquimod. Conclusions: Our study is the first to use the entire transcriptomic profile of ICI myocarditis in both preclinical models and patients for drug discovery. Our results demonstrate that ICI myocarditis has a distinct gene expression profile compared to healthy and other cardiac diseases. By querying a drug-gene interaction database, we identified several novel drug targets and possible treatments for ICI-related cardiotoxicity.
Treatment of several diseases, such as recurrent Clostridioides difficile infection, by faecal microbiota transplanatation (FMT) has increased since 2015. 1 Kelly CR Yen EF Grinspan AM et al. Fecal microbiota transplantation is highly effective in real-world practice: initial results from the FMT National Registry. Gastroenterology. 2021; 160: 183-192 Summary Full Text Full Text PDF PubMed Scopus (49) Google Scholar Because both the technology for and the concept of treating diseases by interfering with gut microbiota are new, clinicians and patients are particularly concerned about treatment safety. To our knowledge, most studies investigating the safety of FMT have focused on short-term risks, which are mild and generally associated with FMT delivery methods. There have been no reports of FMT safety in the treatment of multiple diseases or for long follow-up periods. 2 Mullish BH Quraishi MN Segal JP et al. The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines. Gut. 2018; 67: 1920-1941 Crossref PubMed Scopus (159) Google Scholar , 3 Saha S Mara K Pardi DS Khanna S Long-term safety of fecal microbiota transplantation for recurrent Clostridioides difficile infection. Gastroenterology. 2021; 160: 1961-1969 Summary Full Text Full Text PDF PubMed Scopus (27) Google Scholar
Fecal microbiota transplantation (FMT) is a therapy that involves the transplantation of healthy human fecal microorganisms into the gut of patients to rebuild or consolidate the intestinal microecology. It has been utilized in many diseases. However, FMT had a limited effect on patients with small intestinal diseases because of the unique ecological characteristics of the microorganisms. Thus, we proposed a new microecology transplantation therapy called human intestinal fluid transplantation (HIFT). Human intestinal fluid can be collected through a nasojejunal tube and be made into capsules using the freeze-dried powder method. In addition, strict standards for donor screening and management have been established. We are currently developing a high-standard HIFT preparation system and conducting high-quality clinical studies to validate the safety and efficacy of HIFT combined with FMT.
Inflammatory bowel disease (IBD) is a common chronic remitting disease with no satisfactory treatment. The aim of this study was to investigate the protective effect of α7 nicotinic acetylcholine receptor (α7nAChR), and to determine the underlying mechanism of its activity. The expression and distribution of α7nAChR in the intestinal tissue of patients with ulcerative colitis and Crohn’s disease were analyzed. The effects of vagal excitation on murine experimental colitis were investigated. The colitis model was induced in C57BL/6 mice by the administration of 3% dextran sulfate sodium (DSS). The therapeutic group received treatment with the α7nAChR agonist PNU-282987 by intraperitoneal injection. Our results showed that there was significantly increased expression of α7nAChR in colitis and Crohn’s disease intestinal tissue, and its expression was mainly located in macrophages and neutrophils, which were extensively infiltrated in the disease status. Treatment with an α7nAChR agonist potently ameliorated the DSS-induced illness state, including weight loss, stool consistency, bleeding, colon shortening, and colon histological injury. α7nAChR agonist exerted anti-inflammatory effects in DSS colitis mice by suppressing the secretion of multiple types of proinflammatory factors, such as IL6, TNFα, and IL1β, and it also inhibited the colonic infiltration of inflammatory cells by blocking the DSS-induced overactivation of the NF-κB and MAPK signaling pathways. Mechanistically, activation of α7nAChR decreased the number of infiltrated M1 macrophages in the colitis intestine and inhibited the phagocytosis ability of macrophages, which were activated in response to LPS stimulation. Thus, an α7nAChR agonist ameliorated colonic pathology and inflammation in DSS-induced colitis mice by blocking the activation of inflammatory M1 macrophages.
Objective: To explore the risk factors for early clinical recurrence of inflammatory bowel disease (IBD) after fecal microbiota transplantation (FMT). Methods: A retrospective study was conducted on 192 patients with IBD who received FMT treatment in the Colorectal Disease Specialty/Intestinal Microecology Treatment Center of the Tenth People's Hospital Affiliated to Tongji University from February 2017 to June 2020. Univariate and multivariate logistic regression models were used to analyze the risk factors for early recurrence of inflammation. Feces from all participants were collected to extract the total bacterial genomic DNA. The V6-8 regions of the bacterial 16S rDNA gene were amplified by polymerase chain reaction (PCR), the PCR products were detected by the denaturing gradient gel electrophoresis (DGGE) method, and the intestinal flora was analyzed by DNA fingerprinting. Stool samples from all patients were tested for 9 bacteria, white blood cells (WBC) and platelet (PLT) counts, as well as the erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) level. Results: Of the 192 patients, 15 cases had inflammation recurrence during FMT and within one week after treatment, including 11 cases of ulcerative colitis (UC) and 4 cases of Crohn's disease (CD), with a total recurrence rate of 7.8%. High Mayo inflammatory activity score, Mayo endoscopic sub-item score (MES) =3 points, CRP>10 mg/L, anemia, albumin <30 WL, absolute value of peripheral blood lymphocytes (PBL) <500/mm(3), and intolerance to enteral full nutrition were independent risk factors for recurrence during and after FMT in UC patients (P<0.05). Albumin <30 WL and simultaneous use of immunosuppressive agents were associated with disease recurrence during and after FMT in CD patients. WBC, PLT, and CRP were all negatively correlated with Enterococcus (EC), and ESR was positively correlated with Saccharomyces boulardii (SB) (P<0.01). Conclusion: The low recurrence rate of IBD after FMT indicates the safety of FMT, but this procedure should be cautiously used in patients with severe intestinal barrier dysfunction and/or severe intestinal dysfunction.
Therapeutic application of fecal material has been described as early as 4th century China.1 Subsequently, the intervention has evolved, and fecal microbiota transplantation (FMT) has become a recommended treatment from the American College of Gastroenterology guideline for a second recurrent Clostridioides difficile infection2 and has emerged as a promising intervention to address dysbiosis linked to a number of diseases.3
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Crohn's disease activates the inflammatory reactions to induce intestinal disorders. Enteral nutrition (EN) could exert general immunomodulatory effects. Cecal ligation and perforation (CLP) surgery was utilized to establish Crohn's disease mice models. Survival analysis, hematoxylin-eosin staining, flow cytometry, ELISA, Western blot and liquid chromatography-tandem MS were applied. Baicalein was added to inhibit lipoxygenases. The survival rate was restored and inflammatory injury, exudate neutrophils in peritoneal lavage and serum levels of IL-6 and TNF-α were ameliorated by EN treatment as compared with CLP treatment. EN also increased ILC-3 content, 5/15-LOX level and RvD1-RvD5 in peritoneal lavage. Baicalein reversed all the detected effects of EN except ILC-3 content. EN could activate special pro-resolving mediators (SPMs) through ILCs to mitigate injuries of Crohn's disease.
In the version of this article originally submitted, it was stated that the first three authors (Shaoyi_ Than, Yan Wang, Wei Xie) had contributed equally. However, in the published version this information was missing.
Objectives Intestinal tuberculosis (ITB) remains prevalent and a big health hazard in China. The aim of this study was to retrospectively analyse its clinico-pathological features. Methods Retrospective study of 85 consecutive ITB patients in two tertiary hospitals in East China. Relevant clinical, laboratory examination, radiological, endoscopic and histopathological features of ITB were recorded. Results The mean age was 37.3 +/- 16.0 years; 56 patients (65.9%) were male. 67.1% had ITB secondary to pulmonary tuberculosis. The overall median length of hospital stay was 28 days and was significantly longer in patients with intestinal complications (P = 0.003) and malnutrition (P = 0.042). Abdominal pain (88.2%) and weight loss (75.3%) were the commonest symptoms. The positive rate of the purified protein derivative (PPD) test was 88.2%; of the T-spot, 85.7%. Histopathology revealed caseating granuloma in 70.6% and caseating necrosis in 24.7% of patients. The most commonly affected sites were the ileocecal valve (56, 65.9%), terminal ileum (40, 47.1%) and caecum (33, 38.8%). Only 17 (20%) patients were initially diagnosed as ITB, the other 68 patients were misdiagnosed. Six patients with caecum tuberculosis were misdiagnosed as appendicitis, four of whom had improper surgical procedures followed by post-operative intestinal fistulas; two died due to MODS. Conclusions Diagnosis of ITB is often misdirected and delayed, which may lead to inappropriate treatment and high mortality. High diagnostic suspicion is necessary for patients with unexplained abdominal complaints. Diagnosis is not easy but could benefit coexisting pulmonary tuberculosis, T-spot, CT imaging, colonoscopy, pathological features, acid-fast bacilli and response to anti-tuberculosis therapy (ATT).
To evaluate the feasibility and accuracy of remnant small intestinal length measured by barium follow-through (BaFT) examination and three-dimensional CT enterography (CTe).
Cystic Fibrosis (CF) due to the ΔF508 mutation of cystic fibrosis transmembrane conductance regulator (CFTR) can be treated with a combination of cysteamine and Epigallocatechin gallate (EGCG). Since ECGC is not a clinically approved drug, we attempted to identify other compounds that might favourably interact with cysteamine to induce autophagy and thus rescuing the function of ΔF508 CFTR as a chloride channel in the plasma membrane. For this, we screened a compound library composed by chemically diverse autophagy inducers for their ability to enhance autophagic flux in the presence of cysteamine. We identified the antiarrhythmic Ca2+ channel blocker amiodarone, as an FDA-approved drug having the property to cooperate with cysteamine to stimulate autophagy in an additive manner. Amiodarone promoted the re-expression of ΔF508 CFTR protein in the plasma membrane of respiratory epithelial cells. Hence, amiodarone might be yet another compound for the etiological therapy of CF in patients bearing the ΔF508 CFTR mutation.
Prosthetic mesh used for ventral incisional hernia makes hernia repair surgery simple, effective, and safe. The mesh infection is a formidable complication and bimodal distribution. The differences between early- and late-onset are unknown. This is a cohort study of patients undergoing ventral incisional hernia (VIH) repair from January 2003 to September 2013. Data of specific risk variables were collected from electronic medical record systems in Jinling Hospital. And, the quality of lives was evaluated by WHO Quality of Life-BREF. A total of 102 VIH repair patients were analyzed and followed including the noninfection group and early- and late-onset group. There were significant differences between the early- and late-onset group in clinical manifestation, descriptive analysis of the study population, and postoperative quality of lives. These differences might imply the different pathophysiologic process of early- and late-onset mesh infection. Permanent prosthetic mesh should be used with caution, and the study of intraperitoneal onlay mesh is still needed in long-term follow-up.
Early enteral feeding within 24-48 h of intensive care unit admission is recommended for critically ill patients. This study aimed to determine if early enteral feeding could be safely implemented with purported benefits in patients with abdominal trauma.A retrospective cohort study was performed that included 88 adult patients with abdominal trauma. Patients receiving enteral feeding within 72 h of surgical intensive care unit (SICU) admission (early-initiation group, n = 28) were compared to those receiving enteral feeding later (delayed-initiation group, n = 60).The two groups were comparable in demographic characteristics and injury severity. There were no differences in feeding intolerance (53.6 vs. 43.3 %, p = 0.37) and mortality at 28 days (0 vs. 5 %, p = 0.55) between the early-initiation group and the delayed-initiation group. However, patients in the early-initiation group had fewer infectious complications (17.9 vs. 40 %, p = 0.04) and shorter length of stay in SICU and hospital (p < 0.01) than patients in the delayed-initiation group.Early enteral feeding administered within 72 h of SICU admission was associated with improved clinical outcomes without risk of increasing feeding intolerance in patients with abdominal trauma. Our results support the implementation of early enteral feeding in abdominal trauma management.
Objective To investigate the procedures for establishing a stable model of intestinal xenotransplantation from pig to cynomolgus, with the purpose of providing a good experimental tool for the xenograft rejection study in intestinal xenotransplantation. Methods White wild-type pigs were used as donor and cynomolguses used as recipients. The procedure of segmental heterotopic intestinal xenotransplantation in recipients was performed as following: the donor`s anterior mesenteric artery was anastomosed end-to-side to the recipient`s infrarenal abdominal aorta, and the donor`s tributary of anterior mesenteric venous was anastomosed end-to-side to the recipient`s infrarenal inferior vena cave. Subsequently, both the proximal and distant ends of the graft intestine were stayed ligated. Results Segmental intestinal xenotransplantation was performed in 5 cynomolguses, with an average graft intestine length of (52.0 ± 5.7) cm. The success rate of vascular anastomosis was 100%, and the intestinal xenograft survival was 152±72(55~245) minutes. Conclusions A stable, repeatable model of segmental intestinal xenotransplantation from pig to cynomolgus was established, which would provide an ideal tool for further research on intestinal xenotransplantation from transgenic pig to cynomolgus.
Since its introduction as an alternative intestinal lengthening technique, serial transverse enteroplasty has been increasingly used as the surgical treatment of choice for children with refractory short bowel syndrome, but there have been few reports about the adult patients. This report describes the case of a 71-year-old man with a short bowel after distal gastrectomy with Billroth II reconstruction for gastric cancer, followed by extensive intestinal resection. The serial transverse enteroplasty operation was performed and lengthened the small intestine from 49 to 67 cm. The patient tolerated the procedure well and weaned off total parenteral nutrition. Liver function also improved. This case shows that the serial transverse enteroplasty procedure increases intestinal length. This procedure should be considered a surgical option for adult patients with extreme short bowel syndrome.