Gastroenterology Clinics of North America

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Intestinal failure (IF) remains as a life-threatening medical condition worldwide, but the disparity on the type and quality of medical care available, together with the different limitations to access among individual countries or regions, turned IF assessment and therapy into a difficult matter, which becomes a major hazard for the developing world. This article aims to provide an update regarding definitions used, the current general worldwide data, the developments, achievements, and the different access alternatives in Latin-America, Middle East, and Asia to exemplify what can be done to help patients with IF...

Outcomes in intestinal transplantation remain hampered by higher rates of rejection than any other solid organs. However, maintenance immunosuppression regimens have largely remained unchanged despite advances in therapies for induction and treatment of rejection and graft-versus-host disease. Recently, there have been a small number of new maintenance therapies attempted, and older agents have been used in new ways to achieve better outcomes. The authors herein review the traditional maintenance therapies and their mechanisms and then consider updates in new therapies and new ways of using old therapies for maintenance immunosuppression after intestinal transplantation...

This comprehensive review focuses on advances in surgical techniques and in vivo animal models for treating short bowel syndrome (SBS) with intestinal organoids. Notably, this review discusses a novel method involving the replacement of the epithelium of large intestinal tissue with small intestinal organoids, which improves function and prognosis when grafted back into the small intestine. This study not only underscores the importance of integrating organoid technology and surgical techniques to improve the outcomes of patients with SBS but also acknowledges the challenges that lie ahead, including achieving functional organoids with peristaltic movement and vascularization...

In intestinal resection animal models of short bowel syndrome (SBS), the remaining epithelium mounts a robust adaptive response characterized by early stem cell expansion and increased crypt depth, villus height and nutrient absorption. In humans the adaptive response is critical for resumption of oral nutrition, yet it may be variable, and underlying mechanisms are much less well understood. Current knowledge relating to the role of stem and mesenchymal niche cells in the adaptive response in animal models and in human SBS are addressed in this review...

Intestinal failure manifests as an impaired capacity of the intestine to sufficiently absorb vital nutrients and electrolytes essential for growth and well-being in pediatric and adult populations. Although parenteral nutrition remains the mainstay therapeutic approach, the pursuit of a definitive and curative strategy, such as regenerative medicine, is imperative. Substantial advancements in the field of engineered intestinal tissues present a promising avenue for addressing intestinal failure; nevertheless, extensive research is still necessary for effective translation from experimental benchwork to clinical bedside applications...

The history of intestinal transplantation can be traced back to the turn of the twentieth century. Although advancements have been made, the intestine still presents a greater challenge to transplantation than does that of other solid organs, experiencing higher rates of graft rejection and lower long-term survival. Increasingly, intestinal re-transplantation (re-ITx) is seen as a viable option and is now the fourth most common indication for ITx. Changes to immunosuppression protocols, technical modifications, and infectious disease monitoring have contributed to improved outcomes...

This study explores intestinal transplantation (ITx) as a viable treatment option for intestinal failure (IF). Historical development, donor and recipient considerations, surgical techniques, immunosuppression, and outcomes, are reviewed with particular emphasis to the value of living donor ITx. The review highlights the evolution of ITx and emphasizes the ongoing need for patient-specific selection processes. In the realm of pediatric ITx, the article underlines the significance of early intervention to mitigate IF-related liver disease...

Vaccines should be regularly administered and their efficiency controlled, before and after intestinal transplantation. The household and health care providers should also be immunized, to further prevent transmission. Universal vaccination providing " herd immunity" should be enforced. Recommendations are given about timing, indications, and contraindications of each individual vaccine, before and after transplantation.

In this review, the authors outlined concepts and strategies to achieve immune tolerance through inducing hematopoietic chimerism after solid organ transplantation and introduced challenges and opportunities in harnessing two-way alloresponses to improve outcomes after intestinal transplantation (ITx). Next, the authors discussed the dynamics and phenotypes of peripheral blood and intestinal graft T-cell subset chimerism and their association with outcomes. The authors also summarized studies on other types of immune cells after ITx and their potential participation in chimerism-mediated tolerance...

The microbiota in our gut regulates the sophisticated metabolic system that the human body has, essentially converting food into energy and the building blocks for various bodily functions. In this review, we discuss the multifaceted impact of the microbiota on host nutritional status by producing short-chain fatty acids, influencing gut hormones and mediating bile acid metabolism, and the key role in maintaining intestinal barrier integrity and immune homeostasis. Understanding and leveraging the power of the gut microbiome holds tremendous potential for enhancing human health and preventing various diseases...

The human gut microbiota, consisting of trillions of microorganisms, encodes diverse metabolic pathways that impact numerous aspects of host physiology. One key way in which gut bacteria interact with the host is through the production of small metabolites. Several of these microbiota-dependent metabolites, such as short-chain fatty acids, have been shown to modulate host diseases. In this review, we examine how disease-associated metabolic signatures are identified using metabolomic platforms, and where metabolomics is applied in gut microbiota-disease interactions...

Intestinal transplantation is a life-saving procedure utilized for patients failing total parenteral nutrition. However, intestinal transplantattion remains plagued with low survival rates and high risk of allograft rejection. The authors explore roles of innate (macrophages, natural killer cells, innate lymphoid cells) and adaptive immune cells (Th1, Th2, Th17, Tregs) in inflammatory responses, particularly inflammatory bowel disease and graft versus host disease, and correlate these findings to intestinal allograft rejection, highlighting which effectors exacerbate or suppress intestinal rejection...

Despite advancements in short-term outcomes since the inception of intestinal transplant, significant long-term graft failure persists. Early successes are attributed to the utilization of tacrolimus for maintenance therapy, coupled with T-cell modulating induction regimens, which effectively reduce the incidence of acute cellular rejection. However, the challenge of chronic allograft injury remains unresolved. There is increasing evidence indicating a correlation between donor-specific antibodies and the survival of visceral allografts...

Infants and children with intestinal failure are at risk for pediatric feeding disorders, which challenge their oral feeding development. This article explores these challenges and offers several practical strategies that can be used by multidisciplinary care teams and at-home caregivers to help support the development of oral feeding in these children and eventually lead to their attaining enteral autonomy.

Achieving feeding skills and food acceptance is a multi-layered process. In pediatric intestinal failure (PIF), oral feeding is important for feeding skills development, physiologic adaptation, quality of life and the prevention of eating disorders. In PIF, risk factors for feeding difficulties are common and early data suggests that feeding difficulties are prevalent. There is a unique paradigm for the feeding challenges in PIF. Conventional definitions of eating disorders have limited application in this context...

As we all acknowledge benefits of ostomies, they can come with significant morbidity, quality of life issues, and major complications, especially during reversal procedures. In recent years, we have started to observe that similar graft and patient survival can be achieved without ostomies in certain cases. This observation and practice adopted in a few large-volume transplant centers opened a new discussion about the necessity of ostomies in intestinal transplantation. There is still more time and randomized studies will be needed to better understand and analyze the risk/benefits of "No-ostomy" approach in intestinal transplantation...

Hirschsprung's disease is a dysmotility disease caused by lack of ganglion cells in the bowel wall that can affect varying lengths of the intestine. In extreme circumstances, there can be little remaining ganglionated bowel, and the patient becomes dependent on parental nutrition (PN) for survival. Intestinal transplant has been utilized to salvage these patients suffering terminal complications of PN. The question as to whether to reestablish intestinal continuity, and thus not require a stoma is vexed. However, data and experience would suggest this can be safely done with good functional results...

The traditional procedure for multivisceral transplant (MVT) is to transplant the stomach, pancreas, intestine, and liver en bloc. During surgery, the native spleen is routinely removed from the recipient, and it usually creates more space in the abdomen to insert the allogeneic graft. Thus, recipients often become asplenic after MVT. Considering all of the risks and benefits, we advocate that temporary transplant of the donor spleen could be the best option for MVT recipients; it could potentially reduce the rate of intestinal allograft rejection without increasing the risk for graft-versus-host disease...

Failure to close the abdomen after intestinal or multivisceral transplantation (Tx) remains a frequently occurring problem. Two attractive reconstruction methods, especially in large abdominal wall defects, are full-thickness abdominal wall vascularized composite allograft (AW-VCA) and nonvascularized rectus fascia (NVRF) Tx. This review compares surgical technique, immunology, integration, clinical experience, and indications of both techniques. In AW-VCA Tx, vascular anastomosis is required and the graft undergoes hypotrophy post-Tx...