Translational strategies for oral delivery of faecal microbiota transplantation.

Faecal microbiota transplantation (FMT) has emerged as a transformative therapy for infections and shows promise for various GI and systemic diseases. However, the poor patient acceptability and accessibility of 'conventional' FMT, typically administered via colonoscopies or enemas, hinders its widespread clinical adoption, particularly for chronic conditions. Oral administration of FMT (OralFMT) overcomes these limitations, yet faces distinct challenges, including a significant capsule burden, palatability concerns and poor microbial viability during gastric transit.

A study protocol for a double-blinded, randomised, placebo-controlled trial on the use of encapsulated FMT for reducing the side effects of HSCT: the HSCT-BIOME study.

Background: The composition of the gut microbiota both prior to and after haematopoietic stem cell transplantation (HSCT) is increasingly implicated in the outcomes of HSCT, including infections, poor immune reconstitution and disease relapse. Faecal microbiota transplantation (FMT) offers a potential strategy of supporting the gut microbiota and improve HSCT outcomes. Although FMT has been investigated in HSCT recipients, it has largely been evaluated therapeutically for indications such as infection, or once immunocompetency is regained.

Comparing Long-Term Infliximab Persistence Following a Switch to a Biosimilar in Patients With Inflammatory Bowel Disease: No Cause for Concern.

Introduction: Several studies have demonstrated that switching stable patients with inflammatory bowel disease (IBD) from originator to biosimilar infliximab is noninferior to continuing originator infliximab. However, "real-world" data comparing long-term outcomes between switch and nonswitch cohorts is lacking. This study aimed to address this gap by comparing long-term outcomes in IBD patients across switch and nonswitch cohorts.

Faecal transplantation: the good, the bad and the ugly.

There continues to be significant interest from both clinicians and patients in using faecal transplantation, as the integral role of the gut microbiome is increasingly recognised in various disease conditions, both within and beyond the gut. This Clinical Perspectives article provides an overview of existing literature, factors limiting the use of faecal microbial transplantation in clinical practice and exciting new advancements on the horizon.

Gut microbiota strain richness is species specific and affects engraftment.

Despite the fundamental role of bacterial strain variation in gut microbiota function, the number of unique strains of a species that can stably colonize the human intestine is still unknown for almost all species. Here we determine the strain richness (SR) of common gut species using thousands of sequenced bacterial isolates with paired metagenomes. We show that SR varies across species, is transferable by faecal microbiota transplantation, and is uniquely low in the gut compared with soil and lake environments.

The phageome of patients with ulcerative colitis treated with donor fecal microbiota reveals markers associated with disease remission.

Bacteriophages are influential within the human gut microbiota, yet they remain understudied relative to bacteria. This is a limitation of studies on fecal microbiota transplantation (FMT) where bacteriophages likely influence outcome. Here, using metagenomics, we profile phage populations - the phageome - in individuals recruited into two double-blind randomized trials of FMT in ulcerative colitis.

Refining microbial community metabolic models derived from metagenomics using reference-based taxonomic profiling.

Characterization of microbial community metabolic output is crucial to understanding their functions. Construction of genome-scale metabolic models from metagenome-assembled genomes (MAG) has enabled prediction of metabolite production by microbial communities, yet little is known about their accuracy. Here, we examined the performance of two approaches for metabolite prediction from metagenomes, one that is MAG-guided and another that is taxonomic reference-guided.

Effects of Thiopurine Withdrawal on Vedolizumab-Treated Patients With Ulcerative Colitis: A Randomized Controlled Trial.

Background & Aims: The impact of thiopurine de-escalation while on vedolizumab versus continuing thiopurine therapy in ulcerative colitis (UC) is unclear. We aimed to determine the effect of thiopurine withdrawal for patients with UC in remission on vedolizumab.

Methods: This multicenter randomized controlled trial recruited UC patients on vedolizumab 300 mg intravenously every 8 weeks and a thiopurine.

Microbial determinants of effective donors in faecal microbiota transplantation for UC.

Objective: Faecal microbiota transplantation (FMT) has variable efficacy in treating UC. Recently, oral lyophilised FMT was found to induce remission in patients with UC, with one donor having 100% efficacy compared with a second donor (36% efficacy). We characterised differences in the gut microbiota of these two donors with the aim of improving FMT donor selection.

Lyophilised oral faecal microbiota transplantation for ulcerative colitis (LOTUS): a randomised, double-blind, placebo-controlled trial.

Background: Faecal microbiota transplantation (FMT) delivered via colonoscopic infusion or enemas have been shown to induce remission in a proportion of patients with active ulcerative colitis. Whether orally administered FMT is effective in ulcerative colitis is unknown. We aimed to assess the efficacy of oral lyophilised FMT for the treatment of active ulcerative colitis.

Long-Term Bacterial and Fungal Dynamics following Oral Lyophilized Fecal Microbiota Transplantation in Clostridioides difficile Infection.

Oral lyophilized fecal microbiota transplantation (FMT) is effective in recurrent infection (CDI); however, limited data exist on its efficacy in primary CDI and long-term microbial engraftment. Patients with primary or recurrent CDI were prospectively enrolled to receive oral FMT. Changes in the bacterial and fungal communities were characterized prior to and up to 6 months following treatment.

Switching Australian patients with moderate to severe inflammatory bowel disease from originator to biosimilar infliximab: a multicentre, parallel cohort study.

Objective: To examine whether non-medical switching of patients with inflammatory bowel disease (IBD) from originator infliximab to a biosimilar (CT-P13, Inflectra) is safe and clinically non-inferior to continued treatment with originator infliximab.

Design: Prospective, open label, multicentre, parallel cohort, non-inferiority study in seven Australian hospitals over 48 weeks, May 2017 - October 2019.

Participants: Adults (18 years or older) with IBD receiving maintenance originator infliximab (Remicade) who had been in steroid-free clinical remission for at least 12 weeks.

The role of faecal microbiota transplantation in the treatment of inflammatory bowel disease.

Purpose Of The Review: Faecal microbiota transplantation (FMT) has emerged as a potent form of therapeutic microbial manipulation. There is much interest in exploring its potential in conditions such as inflammatory bowel disease (IBD) where disturbances in the gastrointestinal microbiota play a crucial role in disease pathogenesis.

Recent Findings: There are 4 randomized controlled trials of FMT as induction therapy in ulcerative colitis, with meta-analyses suggesting significant benefit over placebo.

Australian consensus statements for the regulation, production and use of faecal microbiota transplantation in clinical practice.

Objective: Faecal microbiota transplantation (FMT) has proved to be an extremely effective treatment for recurrent infection, and there is interest in its potential application in other gastrointestinal and systemic diseases. However, the recent death and episode of septicaemia following FMT highlights the need for further appraisal and guidelines on donor evaluation, production standards, treatment facilities and acceptable clinical indications.

Design: For these consensus statements, a 24-member multidisciplinary working group voted online and then convened in-person, using a modified Delphi approach to formulate and refine a series of recommendations based on best evidence and expert opinion.

Vitamin D metabolites are lower with active Crohn's disease and spontaneously recover with development of remission.

Background: Vitamin D deficiency is associated with active Crohn's disease (CD). However, it remains unclear if lower 25-hydroxyvitamin D [25(OH)D] concentration is the cause, or consequence, of intestinal inflammation. Existing literature has focused on circulating 25(OH)D rather than the active metabolite 1,25(OH)D, or its breakdown product, 24,25(OH)D.

Safety of drugs used for the treatment of Crohn's disease.

Introduction: Medications in treating Crohn's disease (CD) have evolved over the last two decades, particularly with the use of biologic agents. There are, however, concerns about the safety and adverse events associated with these medications. The authors review the safety profile of immunosuppressive medications used in Crohn's disease in adult patients.

A Global Survey of Gastroenterologists' Travel Advice to Patients with Inflammatory Bowel Disease on Immunosuppressive Agents and Management of Those Visiting Tuberculosis-Endemic Areas.

Background: With increasing use of biological therapies and immunosuppressive agents, patients with inflammatory bowel disease[IBD] have improved clinical outcome and international travel in this group is becoming common. Adequate pre-travel advice is important. We aim to determine the proportion of gastroenterologists who provided pre-travel advice, and to assess their management strategies for patients on biological therapies visiting tuberculosis[TB]-endemic areas.