Intestinal Transplantation Research Articles

A metagenomic prospective cohort study on gut microbiome composition and clinical infection in small bowel transplantation.

Two-thirds of small-bowel transplantation (SBT) recipients develop bacteremia, with the majority of infections occurring within 3 months post-transplant. Sepsis-related mortality occurs in 31% of patients and is commonly caused by bacteria of gut origin, which are thought to translocate across the implanted organ. Serial post-transplant surveillance endoscopies provide an opportunity to study whether the composition of the ileal and colonic microbiota can predict the emergence as well as the pathogen of subsequent clinical infections in the SBT patient population. Five participants serially underwent aspiration of ileal and colonic bowel effluents at transplantation and during follow-up endoscopy either until death or for up to 3 months post-SBT. We performed whole-metagenome sequencing (WMS) of 40 bowel effluent samples and compared the results with clinical infection episodes. Microbiome composition was concordant between participants and timepoint-matched ileal and colonic samples. Four out of five (4/5) participants had clinically significant infections thought to be of gut origin. Bacterial translocation from the gut was observed in 3/5 patients with bacterial infectious etiologies. In all three cases, the pathogens had demonstrably colonized the gut between 1-10 days prior to invasive clinical infection. Recipients with better outcomes received donor grafts with higher alpha diversity. There was an increase in the number of antimicrobial resistance genes associated with longer hospital stay for all participants. This metagenomic study provides preliminary evidence to support the pathogen translocation hypothesis of gut-origin sepsis in the SBT cohort. Ileal and colonic microbiome compositions were concordant; therefore, fecal metagenomic analysis could be a useful surveillance tool for impeding infection with specific gut-residing pathogens.

Indications and results of intestinal transplantation for short bowel syndrome after mesenteric ischemia

Intestinal transplantation (ITx) is the only causal treatment for complicated chronic intestinal failure after mesenteric ischemia and impending failure of parenteral supplementation. Isolated or combined ITx with the inclusion of the intestine is associated with demanding immunological, perioperative and infection associated challenges. The characterization of chronic intestinal failure, the indications, transplant survival, transplantation techniques and success rates. Collection, summary and critical appraisal of international guidelines, the guidelines of the German Medical Chamber, and the international literature. The first successful ITx were performed in 1987 and 1988 at the University of Kiel Germany and the University of Pittsburgh, USA. The number of ITx rose continuously but in phases from the end of the 1990s to over 200 per year but has currently decreased to 100-150 per year due to optimized intestinal rehabilitation. While the 1‑year and 3‑year transplant survival rates were 30% and 20% before 1991, they increased in phases up to 60% and 50%, respectively, after 1995 and have now achieved almost 80% and 70%, respectively. The substantial improvement in the results of ITx can be partly explained by progress in operative techniques, intensive care medicine and a better understanding of mucosal immunity; however, optimized strategies in immunosuppression as well as prevention of infectious diseases and malignancies have also made decisive contributions.

Suppressor T helper type 17 cell responses in intestinal transplant recipients with allograft rejection

BackgroundIntestinal transplant (ITx) rejection is associated with memory T helper type 17 cell (Th17) infiltration of grafted tissues. Modulation of Th17 effector cell response is facilitated by T regulatory (Treg) cells, but a phenotypic characterization of this process is lacking in the context of allograft rejection. MethodsFlow cytometry was performed to examine the expression of surface receptors, cytokines, and transcription factors in Th17 and Treg cells in ITx control (n = 34) and rejection patients (n = 23). To elucidate key pathways guiding the rejection biology, we utilized RNA sequencing (RNAseq) and assessed epigenetic stability through pyrosequencing of the Treg-specific demethylated region (TSDR). ResultsWe found that intestinal allograft rejection is characterized by Treg cellular infiltrates, which are polarized toward Th17-type chemokine receptor, ROR-γt transcription factor expression, and cytokine production. These Treg cell subsets have maintained epigenetic stability, as defined by FoxP3-TSDR methylation status, but displayed upregulation of functional Treg and purinergic signaling genes by RNAseq analysis such as CD39, in keeping with suppressor Th17 properties. ConclusionWe show that ITx rejection is associated with increased polarized cells that express a Th17-like phenotype concurrent with regulatory purinergic markers.

Including the liver in the visceral allograft: Impact on donor-specific anti-HLA antibodies and long-term outcomes

Humoral immunity emerges as a risk factor for graft failure after visceral transplantation (VTx) and development of donor-specific anti-HLA antibodies (DSAs) has been linked with poor outcomes. In most cases, a simultaneous liver transplant can be safely performed in sensitized patients with DSA and appears protective against lymphocytotoxic antibodies. We investigated the incidence of acute (AR) and chronic rejection (CR) in 32 VTx without any B cell-depleting pre-treatment (6 isolated intestinal transplants (IT) and 26 liver-containing, multivisceral transplants (MVT) and assessed the presence of donor-specific antibodies (DSA) pre- and post-transplantation. Twenty-one patients (65 %) developed AR, 15 (57 %) of the MVT and 6 (100 %) of the IT (p = 0.05). CR occurred in 4 IT (60 %, p < 0.001). At one month, de novo DSA were present in 71 % of VTx (66 % MVT vs 100 % IT, p = 0.09). At the last available follow-up, 69 % of the MVT and 50 % of the IT patients were DSA-free. De novo DSA seemed more persistent (7/19, 37 %) than pre-Tx DSA (1/6, 17 %; p = n.s.), de novo DSA were more frequently specific for HLA class II than class I, 16/19 (84 %) vs. 7/19 (37 %; p = 0.003), and HLA-DQ was their most frequent target HLA. DQ mismatches appeared to be a risk factor for developing de novo DSA. In conclusion, liver-containing visceral allografts have superior short- and long-term outcomes compared with liver-free allografts. De novo DSA develop early and frequently after VTx performed without B cell-depleting induction therapy, but the exact role of DSA in the pathogenesis of rejection remains unclear.

Dynamic establishment of recipient resident memory T cell repertoire after human intestinal transplantation

Understanding formation of the human tissue resident memory T cell (TRM) repertoire requires longitudinal access to human non-lymphoid tissues. By applying flow cytometry and next generation sequencing to serial blood, lymphoid tissue, and gut samples from 16 intestinal transplantation (ITx) patients, we assessed the origin, distribution, and specificity of human TRMs at phenotypic and clonal levels. Donor age ≥1 year and blood T cell macrochimerism (peak level ≥4%) were associated with delayed establishment of stable recipient TRM repertoires in the transplanted ileum. T cell receptor (TCR) overlap between paired gut and blood repertoires from ITx patients was significantly greater than that in healthy controls, demonstrating increased gut-blood crosstalk after ITx. Crosstalk with the circulating pool remained high for years of follow-up. TCR sequences identifiable in pre-Tx recipient gut but not those in lymphoid tissues alone were more likely to populate post-Tx ileal allografts. Clones detected in both pre-Tx gut and lymphoid tissue had distinct transcriptional profiles from those identifiable in only one tissue. Recipient T cells were distributed widely throughout the gut, including allograft and native colon, which had substantial repertoire overlap. Both alloreactive and microbe-reactive recipient T cells persisted in transplanted ileum, contributing to the TRM repertoire. Our studies reveal human intestinal TRM repertoire establishment from the circulation, preferentially involving lymphoid tissue counterparts of recipient intestinal T cell clones, including TRMs. We have described the temporal and spatial dynamics of this active crosstalk between the circulating pool and the intestinal TRM pool. This study was funded by the National Institute of Allergy and Infectious Diseases (NIAID) P01 grant AI106697.

Enhanced Donor Antigen Presentation by B Cells Predicts Acute Cellular Rejection and Late Outcomes After Transplantation.

Enhanced B-cell presentation of donor alloantigen relative to presentation of HLA-mismatched reference alloantigen is associated with acute cellular rejection (ACR), when expressed as a ratio called the antigen presenting index (API) in an exploratory cohort of liver and intestine transplant (LT and IT) recipients. To test clinical performance, we measured the API using the previously described 6-h assay in 84 LT and 54 IT recipients with median age 3.3 y (0.05-23.96). Recipients experiencing ACR within 60 d after testing were termed rejectors. We first confirmed that B-cell uptake and presentation of alloantigen induced and thus reflected the alloresponse of T-helper cells, which were incubated without and with cytochalasin and primaquine to inhibit antigen uptake and presentation, respectively. Transplant recipients included 76 males and 62 females. Rejectors were tested at median 3.6 d before diagnosis. The API was higher among rejectors compared with nonrejectors (2.2 ± 0.2 versus 0.6 ± 0.04, P value = 1.7E-09). In logistic regression and receiver-operating-characteristic analysis, API ≥1.1 achieved sensitivity, specificity, and positive and negative predictive values for predicting ACR in 99 training set samples. Corresponding metrics ranged from 80% to 88% in 32 independent posttransplant samples, and 73% to 100% in 20 independent pretransplant samples. In time-to-event analysis, API ≥1.1 predicted higher incidence of late donor-specific anti-HLA antibodies after API measurements in LT recipients (P = 0.011) and graft loss in IT recipients (P = 0.008), compared with recipients with API <1.1, respectively. Enhanced donor antigen presentation by circulating B cells predicts rejection after liver or intestine transplantation as well as higher incidence of DSA and graft loss late after transplantation.

Representation of Women Authorship in the Top 5 Transplantation Journals in the United States.

In the United States, only 13% of transplant surgeons are women. We evaluated gender distribution and trends of American authorship over the past 10 y in high-impact solid organ transplantation journals to gain insight into the current status of women authorship in transplantation. Original articles from 2012 to 2021 from the 5 highest-impact solid organ transplantation journals were extracted from Scopus. First and last author's gender was predicted using Genderize.io. Data of first and last authors, article type and topic, location, citation, and funding metrics were analyzed. Chi-square, logistic regression, and trend tests were performed where appropriate. Statistical significance was set at <0.05. Women's first and last authorship increased over time among all journals. There was an increase in women first authors in the American Journal of Transplantation and in senior women authors in Liver Transplantation and Transplantation . Significant differences in gender authorship in lung, intestine, pancreas, general, and islet cell transplantation were found. Women's last authorship was associated with 1.69 higher odds of having a woman first author when adjusting for year and journal. There was an increase in the rate of women's first and last author collaborations over the years. Women last authors had 1.5 higher odds of being funded by the National Institutes of Health over the years. Despite an increase in women transplant surgeons and physicians, the gap in women authorship in transplantation persists. Women's last authorship was associated with higher odds of having a woman first author, pointing to the importance of mentorship for women joining the transplant academia.

Si-based agent alleviated small bowel ischemia–reperfusion injury through antioxidant effects

The progression of small bowel ischemia–reperfusion (IR) injury causes cells in the intestinal tract to undergo necrosis, necessitating surgical resection, which may result in loss of intestinal function. Therefore, developing therapeutic agents that can prevent IR injury at early stages and suppress its progression is imperative. As IR injury may be closely related to oxidative stress, antioxidants can be effective therapeutic agents. Our silicon (Si)-based agent, an antioxidant, generated a large amount of hydrogen in the intestinal tract for a prolonged period after oral administration. As it has been effective for ulcerative colitis, renal failure, and IR injury during skin flap transplantation, it could be effective for small intestinal IR injury. Herein, we investigated the efficacy of an Si-based agent in a mouse model of small intestinal IR injury. The Si-based agent suppressed the apoptosis of small intestinal epithelial cells by reducing the oxidative stress induced by IR injury. In addition, the thickness of the mucosal layer in the small intestine of the Si-based agent-administered group was significantly higher than that in the untreated group, revealing that Si-based agent is effective against small intestinal IR injuries. In the future, Si-based agents may improve the success rate of small intestine transplantation.

Impact of the diet in the gut microbiota after an inter-species microbial transplantation in fish

Inter-species microbial transplantations offer the possibility of transferring species-specific microbes and their associated functionality. As a conceptual approach, an intestinal microbiota transplant (IMT) between two marine carnivorous fish species that thrive in different environmental conditions was conducted: from donor Atlantic salmon (Salmo salar) to recipient gilthead seabream (Sparus aurata), after obliterating its basal microbiota with an antibiotic treatment. To confirm that the gut microbiota was able to recover after antibiotics without the influence of the diet, a group of gilthead seabream not submitted to the IMT was kept fasted as an internal control. To assess the effect of the diet after the IMT, two groups of gilthead seabream were respectively fed with their typical diet and with Atlantic salmon diet. At 36 days post-IMT, the gut of the individuals fed with their typical diet was dominated by the feed-associated bacteria, while those fed with the salmon diet had developed a unique microbiota from the convergence of the diet, donor, and recipient microbiota. These results suggested that an intestinal microbiota transplantation may be effective if the basal microbiota from the gut is first cleared and a targeted dietary modification is provided to maintain and enrich the novel bacteria species over time.

Role of Complement-dependent Cytotoxicity Crossmatch and HLA Typing in Solid Organ Transplant.

Solid organ transplantation is a life-saving medical operation that has progressed greatly because of developments in diagnostic tools and histocompatibility tests. Crossmatching for complement-dependent cytotoxicity (CDC) and human leukocyte antigen (HLA) typing are two important methods for checking graft compatibility and reducing the risk of graft rejection. HLA typing and CDC crossmatching are critical in kidney, heart, lung, liver, pancreas, intestine, and multi-organ transplantation. A systematic literature search was conducted on the internet, using PubMed, Scopus, and Google Scholar databases, to identify peer-reviewed publications about solid organ transplants, HLA typing, and CDC crossmatching. Recent advances in HLA typing have allowed for high-resolution evaluation, epitope matching, and personalized therapy methods. Genomic profiling, next-generation sequencing, and artificial intelligence have improved HLA typing precision, resulting in better patient outcomes. Artificial intelligence (AI) driven virtual crossmatching and predictive algorithms have eliminated the requirement for physical crossmatching in the context of CDC crossmatching, boosting organ allocation and transplant efficiency. This review elaborates on the importance of HLA typing and CDC crossmatching in solid organ transplantation.

Mesenchymal Stem Cell Extracellular Vesicles as a New Treatment Paradigm in Solid Abdominal Organ Transplantation: A Case Series.

Solid abdominal organ transplantation is fraught with variable rates of rejection and graft versus host disease (GVHD). We sought to determine the safety and efficacy of an advanced extracellular vesicle (EV) investigational product (IP) derived from mesenchymal stem cells (MSC) in the transplant patient population. Seven separate emergency investigational new drug (eNIDs) were filed with the Food and Drug Administration (FDA) for the emergency treatment of rejection of an isolated intestinal graft (n = 2), liver allograft graft (n = 2), modified multivisceral graft (n = 3), and GVHD in isolated intestinal transplant patients (n = 2). Fifteen milliliters of IP was administered intravenously on Day 0, 2, 4, and this treatment cycle was repeated up to four times in each patient depending on the treatment protocol allowed by the FDA. Safety (adverse event reporting) and efficacy (clinical status, serologies, and histopathology) were evaluated. There were no adverse events related to IP. All patients had improvement in clinical symptoms within 24 h, improved serologic laboratory evaluation, improved pulmonary symptoms and dermatologic manifestations of GVHD, and complete histologic resolution of graft inflammation/rejection within 7 days of IP administration. Systemic use of a MSC-derived EV IP was successful in achieving histological clearance of intestinal, liver, and multivisceral graft inflammation, and skin and pulmonary manifestations of GVHD.

P643 Magnifying Endoscopy with Narrow Band Imaging for Graft Failure and Disease Recurrence in Patients with Crohn’s Disease after Intestinal Transplantation

Abstract Background Crohn’s disease (CD) is one of the common causes of short bowel syndrome (SBS) and intestinal failure (IF). Intestinal transplantation (IT) is sometimes needed for patients with CD who develop IF after multiple intestinal resections due to CD-related complications, such as uncontrollable bleeding and penetrating diseases. However, there have been limited case reports concerning the endoscopic surveillance of CD patients after IT. Methods We retrospectively investigated two patients with CD who underwent IT because of SBS-IF after multiple intestinal resection. We administered post-transplantation immunosuppressants and conducted regular magnifying endoscopy with narrow-band imaging (ME-NBI) via ileostomy chimney for surveillance of grafte rejection. Endoscopic prediction of rejection were based on our previously published "VENCH" score which is composed of five parameters: "V" (villi appearance), "E" (erythema), "N" (capillary network), "C" (crypt widening), and "H" (heterogeneity). Endoscopic biopsy were taken for histologic confirmation of graft rejection severity. Results Case 1 was a 60-year-old male patient with CD who received three times of intestinal resection for small bowel stricture and perforation, followed by IT due to SBS-IF. He lived uneventful until seven years thereafter with bloody diarrhea presented. Endoscopic surveillance revealed normal VENCH score of background mucosa but deep longitudinal ulcers which was indicative of recurrence of CD rather than graft rejection. Anti-tumor necrosis factor alpha with adalimumab was prescribed and his diarrhea and graft ulcers improved. Case 2 was a 39-year-old male patient with CD who received extensive intestinal resection due to multiple perforations, followed by IT because of SBS-IF. Endoscopic surveillance revealed normal VENCH score without histologic graft rejection two years thereafter. Both enrolled cases demonstrated favorable outcomes after endoscopic surveillance of intestinal graft with ME-NBI and management accordingly. Conclusion The post IT follow-up of CD patients remains challenging. We highlight the usefulness of the ME-NBI using VENCH score for early detection of graft rejection and its value in monitoring CD patients after IT. Additionally, ulcerations without changes in morphology of surrounding villi should take into consideration the disease recurrence of underlying CD. Further research is needed in endoscopic follow-up and molecular genetics to better understand CD after IT.

Proceedings of the 28th Annual Congress of the International Liver Transplantation Society.

The 2023 Joint International Congress of the International Liver Transplantation Society (ILTS), the European Liver and Intestine Transplant Association (ELITA), and the Liver Intensive Care Group of Europe (LICAGE) held in Rotterdam, the Netherlands, marked a significant recovery milestone for the liver transplant community after COVID-19. With 1159 participants and a surge in abstract submissions, the event focused on "Liver Disorders and Transplantation: Innovations and Evolving Indications." This conference report provides a comprehensive overview of the key themes discussed during the event, encompassing Hepatology, Anesthesia and Critical Care, Acute Liver Failure, Infectious Disease, Immunosuppression, Pediatric Liver Transplantation, Living Donor Liver Transplantation, Transplant Oncology, Surgical Approaches, and Machine Perfusion. The congress provided a platform for extensive discussions on a wide range of topics, reflecting the continuous advancements and collaborative efforts within the liver transplant community.

Current Advances in Graft-versus-host Disease After Intestinal Transplantation.

Graft-versus-host disease (GvHD) remains a potentially fatal complication following intestinal transplant (ITx). Over the past decade, advances in the understanding of the pathophysiology of this complex immunological phenomenon have led to the reassessment of the host systemic immune response and have created a gateway for novel preventive and therapeutic strategies. Although sufficient evidence dictates the use of corticosteroids as a first-line option, the treatment for refractory disease remains contentious and lacks a standardized therapeutic approach. Timely diagnosis remains crucial, and the advent of chimerism detection and immunological biomarkers have transformed the identification, prognostication, and potential for survival after GvHD in ITx. The objectives of the following review aim to discuss the clinical and diagnostic features, pathophysiology, advances in immune biomarkers, as well as therapeutic opportunities in the prevention and treatment of GvHD in ITx.

Treatment of Complex Desmoid Tumors in Familial Adenomatous Polyposis Syndrome by Intestinal Transplantation.

Desmoid tumors are fibroblastic lesions which often have an unpredictable and variable clinical course. In the context of familial adenomatous polyposis (FAP), these frequently occur intra-abdominally, especially in the small-bowel mesentery resulting in sepsis, fistulation, and invasion of the abdominal wall and retroperitoneum. In selected cases where other modalities have failed, the most radical option is to perform a total enterectomy and intestinal transplantation (ITx). In this study, we present our center's experience of ITx for desmoid in patients with FAP. We performed a retrospective review of our prospectively collected database between 2007 and 2022. All patients undergoing ITx for FAP-related desmoid were included. Between October 2007 and September 2023, 144 ITx were performed on 130 patients at our center. Of these, 15 patients (9%) were for desmoid associated with FAP (7 modified multivisceral transplants, 6 isolated ITx, and 2 liver-containing grafts). The median follow-up was 57 mo (8-119); 5-y patient survival was 82%, all with functioning grafts without local desmoid recurrence. These patients presented us with several complex surgical issues, such as loss of abdominal domain, retroperitoneal/abdominal wall involvement, ileoanal pouch-related issues, and the need for foregut resection because of adenomatous disease. ITx is a viable treatment in selected patients with FAP and extensive desmoid disease. The decision to refer for ITx can be challenging, particularly the timing and sequence of treatment (simultaneous versus sequential exenteration). Delays can result in additional disease burden, such as secondary liver disease or invasion of adjacent structures.

Effect of intestinal microbiota on myocardial resistance to ischemia-reperfusion injury

The last 10–15 years have been marked by a rapid increase in the volume of knowledge about the role of the intestinal microbiota in the regulation of various physiological processes. In particular, the interrelations between disturbances in the composition of the intestinal microflora and an increase in the risk of developing cardiovascular diseases were noted. There are also emerging works that demonstrate the possibility of reducing the severity of myocardial ischemia-reperfusion injury as a result of various effects on the composition of intestinal microbiota. This review analyzes the recent literature on the influence of intestinal microbiota on myocardial resistance to ischemia-reperfusion injury. It has been shown that modulation of the intestinal microbiome by changing the nature of nutrition, probiotics, antibiotics, and intestinal microflora transplantation leads to a reduction in the size of myocardial infarction. Normalization of increased permeability of intestinal epithelial barrier with reduction of manifestations of systemic inflammation, changes in the level of secretion of some hormones, increased production of short-chain fatty acids and modulation of bile acid metabolism under the action of intestinal bacterial enzymes are considered as possible mechanisms of cardioprotection mediated by changes in the functional state of microbiota. The concept of increasing myocardial resistance to ischemia-reperfusion injury by modulating the composition of the intestinal microbiota is a completely new scientific direction that requires detailed study in experiment with the possibility of rapid implementation of the results obtained in clinical practice.

A multicentric observational retrospective study on patients with short bowel syndrome and chronic intestinal failure who underwent intestinal transplantation in Brazil

IntroductionShort Bowel Syndrome (SBS) is a rare gastrointestinal disorder associated with Intestinal Failure (SBS‐IF) that leads to morbidity, mortality, and a burden on healthcare costs. Intestine Transplantation (IT) is a treatment option for patients with SBS-IF as it replaces the missing or diseased intestine and offers the potential for return to normal activities and intestinal function. This study aims to describe the clinical course and demographical and clinical characteristics of subjects with SBS-IF who underwent IT in Brazil. MethodsThis retrospective observational study included all SBS-IF patients who underwent IT in two reference centers in Brazil from April 2011 to December 2021. ResultsA total of 7 young male participants were included in the study. The most frequent underlying condition was surgical complications, followed by intestinal volvulus and incisional hernia. The most frequent indication for IT was a hepatic disease associated with total Parenteral Nutrition (PN). The main type of IT performed was intestine only. The median time from underlying condition to IT was 67.3 (16.5‒88.5) months. The mean (SD) number of yearly hospitalizations per patient was 0.5 (0.3). The most common reason for hospitalization was PN-related complications. Sixty exams were performed in-hospital and 53 in the outpatient setting. ConclusionThe findings of this study may be helpful to understand better the journey of patients with SBS-IF to IT in Brazil, providing real-world evidence to develop health policy guidelines and improve the quality of life of these patients.

Risk factors for renal dysfunction after isolated intestinal transplantation.

Kidney dysfunction is a known complication of intestinal transplantation; however, the rate of development and risk factors for chronic kidney disease (CKD) remain poorly defined. This was a single-center retrospective review of isolated adult intestinal allograft recipients from 2011 to 2019. Patients who died or experienced graft loss within 1-year or had a prior transplant were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation at 0-, 6- and 12-months post-transplant, and multivariable linear regression was performed to identify variables associated with adjusted eGFR at 1-year. Independent variables included age, ethnicity, BMI, history of diabetes/hypertension, vasopressor use, TPN and stoma days, urinary or bloodstream infections, intravenous contrast exposure, rejection, concomitant immunosuppression, and time above the therapeutic range of tacrolimus. Variables with a p<.1 in univariate analysis were considered for multivariable modeling. Thirty-three patients were included with a mean age of 43.9±13.0. A mean 42.3% decline in eGFR was observed at 1-year post-transplant, with 15.2% of patients developing new stage 4/5 CKD. Factors associated with a greater decline in adjusted eGFR in the univariate model included increasing age, decreased BMI, stoma days, and vasopressor use. In the adjusted multivariable model patient age (β=-.77, p<.01) and stoma days (β=-.06, p<.01) remained significant. Tacrolimus and sirolimus exposure were not associated with decline in eGFR at 1 year. Renal dysfunction is common following intestinal transplantation. The need for stoma creation should be carefully considered, and reversal should be performed when feasible for renal protection.

Synchronous Abdominal Wall and Small Bowel Transplantation: Critical Insights at 4-Year Follow-up

AbstractThis 4-year follow-up of synchronous abdominal wall vascular composite allotransplantation (AW-VCA) and small bowel transplantation reveals novel insights and innovations in abdominal wall VCA. The case, involving a 37-year-old male Army veteran, showcases the benefits of AW-VCA in addressing loss of abdominal domain in intestinal transplantation (ITx). The events leading to ultimate rejection of both the AW-VCA and small bowel graft at 4 years highlights the complex interplay between graft survival, patient compliance, and immunosuppressive management. Notably, a significant discordance between AW-VCA and ITx rejection patterns was identified, questioning the reliability of skin components in AW-VCA as early indicators of ITx rejection. Furthermore, the behavior of the vascularized abdominal fascia, observed postexcision of the small bowel graft, offers new understanding of the immunologic response to fascia-only grafts. This follow-up emphasizes the complexities of graft survival, patient compliance, and immunosuppressive management, underscoring the need for ongoing research and innovation in the field.

Effect of intestinal microbiota transplantation on chronic hepatitis B virus infection associated liver disease.

Research on the effects of intestinal microbiota transplantation (IMT) on chronic HBV infection (CHB) progression associated liver disease (HBV-CLD) and alterations in the microbiota post-IMT are quite limited for the moment. By integrating microbiome with metabolome analyses, we aimed to the function of IMT and the alterations of gut microbiota in patients with HBV-CLD. First, this study included 20 patients with HBV-CLD and ten healthy controls. Then, 16 patients with CHB were given IMT with donor feces (heterologous) via oral capsule. Fecal samples from CHB patients were obtained before and after IMT, as well as healthy controls, for 16S rDNA sequencing and untargeted metabolomics analysis. The proalbuminemia were significantly increased after IMT, and the HBsAg and TBA showed a significant decrease after IMT in the HBV-CLD patients. There was statistical difference in the Chaol indexes between between CHB patients and healthy controls, suggesting a lower abundance of the gut microbiota in HBV-CLD patients. In addition, there was statistical difference in the Shannon and Simpson indexes between prior to IMT and post-IMT, indicating that the impaired abundance of the gut microbiota had been improved after IMT. The host-microbiota-metabolite interplay, amino acid metabolism, nicotinate and nicotinamide metabolism, starch and sucrose metabolism, steroid biosynthesis, and vitamins metabolism, were significantly lower in HBV-CLD patients than healthy controls. IMT may improve the therapeutic effects on patients HBV-CLD. Furthermore, IMT appears to improve amino acid metabolism by impaired abundance of the gut microbiota and therefore improve liver prealbumin synthesis.