This topic issue will cover the frontiers in IBD therapy, from diagnostics guiding therapy, prioritising biologics, fecal transfer, real world versus study world to ambulatory versus hospital care as well as novel surgical and pyschological issues in IBD. Additional manuscripts in this area of IBD therapy are very welcome and should be submitted by October 2022. Coeditors are myself (Chief section editor), Klaus Herrlinger and Thomas Klag, both associate editors of Therapy in Gastroenterology.

University Hospital and Faculty of Medicine, University of Tübingen

Asklepios Klinik Nord Heidberg

Exploring new pathways in IBD treatments with a team of experts

. Inflammatory bowel diseases (IBD) are a complex and chronic condition, and research over the past 20 years has led to the development of new treatments and therapies. This research topic focuses on the gender differences in IBD, the importance of immunosuppression, close monitoring of patients, the use of fecal microbiota transfer, and the potential of complementary and alternative medicine to reduce symptom burden. <ul> <li>Gender differences in IBD are most significant in psychosocial functioning, with women being more frequently and severely affected by depression, fatigue, anxiety disorders, eating disorders, and sexual dysfunction.</li> <li>Immunosuppression is key to preventing progressive tissue destruction and permanent disability in IBD patients, however, there is a need for reliable classification of patients based on their biosignature to rate their individual prognosis and likelihood of response to a given therapy.</li> <li>Close and tight monitoring of patients with IBD has become increasingly important, with emerging evidence demonstrating the added clinical value of transmural assessment and the increasing importance of intestinal ultrasound. Non-invasive monitoring modalities are becoming increasingly relevant, and a potential algorithm to monitor patients with IBD in daily clinical practice has been proposed.</li> <li>Ulcerative colitis is a chronic inflammatory bowel disease with an unclear etiology, and fecal microbiota transfer has been shown to be an effective and safe treatment. However, the large-scale application of FMT is limited by the need for healthy donors and associated medicolegal requirements.</li> <li>Complementary and alternative medicine has become a field of interest for gastroenterologists to reduce symptom burden in IBD patients.</li> </ul>

Frontiers in Gastroenterology

Therapy in Gastroenterology

New Frontiers in IBD Therapy

This review provides an overview of the current data regarding sex- and gender-specific aspects in patients with inflammatory bowel diseases. A particular focus will be on disease course, medical and surgical treatment strategies, psychosocial differences, and special requirements during pregnancy and family planning. The most significant and clinically meaningful gender differences in IBD relate to psychosocial functioning. Although depression, fatigue, anxiety disorders, eating disorders, and sexual dysfunction also occur in male IBD patients, women seem to be affected much more frequently and severely in these areas.

This review provides an overview of the current data regarding sex- and gender-specific aspects in patients with inflammatory bowel diseases. A particular focus will be on disease course, medical and surgical treatment strategies, psychosocial differences, and special requirements during pregnancy and family planning. The most significant and clinically meaningful gender differences in IBD relate to psychosocial functioning. Although depression, fatigue, anxiety disorders, eating disorders, and sexual dysfunction also occur in male IBD patients, women seem to be affected much more frequently and severely in these areas.

Sex- and gender-related differences in inflammatory bowel diseases

In light of potentially aggressive disease courses of either IBD type—CD or UC—marked by frequent flareups or non-subsiding inflammatory activity, effective immunosuppression is key to preventing progressive tissue destruction and permanent disability. However, over-treating patients with a high probability of an indolent disease course ought to be avoided. To solve this therapeutic dichotomy, there is a pressing need for a reliable classification of patients based on their biosignature to rate their individual prognosis and likelihood of response to a given therapy. This need for pinpoint therapeutic strategies is addressed by the concepts of PreM and the more stringently defined PerM. In this review we summarize the most pivotal study results published so far in the field of individualized IBD care with a special focus on molecular diagnostics and their applicability in the clinical setting.

In light of potentially aggressive disease courses of either IBD type&#x2014;CD or UC&#x2014;marked by frequent flareups or non-subsiding inflammatory activity, effective immunosuppression is key to preventing progressive tissue destruction and permanent disability. However, over-treating patients with a high probability of an indolent disease course ought to be avoided. To solve this therapeutic dichotomy, there is a pressing need for a reliable classification of patients based on their biosignature to rate their individual prognosis and likelihood of response to a given therapy. This need for pinpoint therapeutic strategies is addressed by the concepts of PreM and the more stringently defined PerM. In this review we summarize the most pivotal study results published so far in the field of individualized IBD care with a special focus on molecular diagnostics and their applicability in the clinical setting.

Molecular medicine-based IBD treatment strategies—we take it personally!

In the current treat-to-target era, close and tight monitoring of patients with inflammatory bowel disease has become increasingly important. Although the importance of patient reported outcomes (PROMs) cannot be underestimated, its moderate association with biochemical and histo-endoscopic outcomes highlights the need for additional monitoring strategies. Endoscopic and histological remission are linked with improved long-term outcomes, but require more invasive assessments. Hence, non-invasive monitoring modalities are becoming increasingly relevant, with emerging evidence demonstrating the added clinical value of transmural assessment, both in Crohn’s disease and ulcerative colitis. The current review covers the multiple treatment targets present in IBD care, and focusses in particular on the increasing importance of intestinal ultrasound. Finally, we propose a potential algorithm to monitor patients with IBD in daily clinical practice and highlight gaps for future research in monitoring IBD strategies.

In the current treat-to-target era, close and tight monitoring of patients with inflammatory bowel disease has become increasingly important. Although the importance of patient reported outcomes (PROMs) cannot be underestimated, its moderate association with biochemical and histo-endoscopic outcomes highlights the need for additional monitoring strategies. Endoscopic and histological remission are linked with improved long-term outcomes, but require more invasive assessments. Hence, non-invasive monitoring modalities are becoming increasingly relevant, with emerging evidence demonstrating the added clinical value of transmural assessment, both in Crohn&#x2019;s disease and ulcerative colitis. The current review covers the multiple treatment targets present in IBD care, and focusses in particular on the increasing importance of intestinal ultrasound. Finally, we propose a potential algorithm to monitor patients with IBD in daily clinical practice and highlight gaps for future research in monitoring IBD strategies.

Monitoring of patients with active inflammatory bowel disease

Ulcerative colitis (UC) is one of the main forms of chronic inflammatory bowel disease; however, despite intensive efforts, its etiology remains unclear. It is generally accepted that disturbances in the gastrointestinal microbiota (“dysbiosis”) contribute to the manifestation and perpetuation of UC. To date, treatment has focused on anti-inflammatory strategies; however, their widespread application is limited by side effects and primary/secondary loss of response. Following the resounding success of fecal microbiota transfer (FMT) to treat Clostridioides difficile infection (CDI), numerous studies have shown that FMT is also effective and safe in UC patients. In this review, we discuss the various modifications (e.g., antibiotic preconditioning, multi-donor concept, extension/intensification of application, long-term therapy, and dietary donor conditioning) that increase the efficacy of FMT. We then describe how the continuous need for healthy donors and the associated medicolegal requirements, limit the large-scale application of FMT. We conclude that FMT will likely be viewed as a transitional technology, which will be superceded by recombinantly produced bioproducts once the therapeutically active substances have been identified.

Ulcerative colitis (UC) is one of the main forms of chronic inflammatory bowel disease; however, despite intensive efforts, its etiology remains unclear. It is generally accepted that disturbances in the gastrointestinal microbiota (“dysbiosis”) contribute to the manifestation and perpetuation of UC. To date, treatment has focused on anti-inflammatory strategies; however, their widespread application is limited by side effects and primary/secondary loss of response. Following the resounding success of fecal microbiota transfer (FMT) to treat Clostridioides difficile infection (CDI), numerous studies have shown that FMT is also effective and safe in UC patients. In this review, we discuss the various modifications (e.g., antibiotic preconditioning, multi-donor concept, extension/intensification of application, long-term therapy, and dietary donor conditioning) that increase the efficacy of FMT. We then describe how the continuous need for healthy donors and the associated medicolegal requirements, limit the large-scale application of FMT. We conclude that FMT will likely be viewed as a transitional technology, which will be superceded by recombinantly produced bioproducts once the therapeutically active substances have been identified.

Fecal microbiota transfer to treat ulcerative colitis: Medical and legal challenges

Inflammatory bowel diseases (IBD) are chronic disabling conditions with a complex and multifactorial etiology, which is still not completely understood. In the last 20 years, anti-TNF-α antagonists have revolutionized the treatment of IBD, but many patients still do not respond or experience adverse events. Therefore, new biological therapies and small molecules, targeting several different pathways of gut inflammation, have been developed of which some have already been introduced in clinical practice while many others are currently investigated. Moreover, therapeutic procedures such as leukocytapheresis, fecal microbiota transplant and stem cell transplantation are currently being investigated for treating IBD. Lastly, complementary and alternative medicine has become a field of interest for gastroenterologist to reduce symptom burden in IBD patients. In this comprehensive and updated review, a novel classification of current and developing drugs is provided.

Inflammatory bowel diseases (IBD) are chronic disabling conditions with a complex and multifactorial etiology, which is still not completely understood. In the last 20 years, anti-TNF-&#x3b1; antagonists have revolutionized the treatment of IBD, but many patients still do not respond or experience adverse events. Therefore, new biological therapies and small molecules, targeting several different pathways of gut inflammation, have been developed of which some have already been introduced in clinical practice while many others are currently investigated. Moreover, therapeutic procedures such as leukocytapheresis, fecal microbiota transplant and stem cell transplantation are currently being investigated for treating IBD. Lastly, complementary and alternative medicine has become a field of interest for gastroenterologist to reduce symptom burden in IBD patients. In this comprehensive and updated review, a novel classification of current and developing drugs is provided.