PRIM-DJ2727 / UT Health Science Center - LARVOL DELTA

Determinants of Treatment Refractoriness in Immune-Mediated Diarrhea and Colitis Following Immune Checkpoint Inhibitor Therapy (ACG 2025) - "Selective immunosuppressive therapy (SIT) with infliximab (IFX) or vedolizumab (VDZ) is often required...Severe clinical, endoscopic, or histologic features may warrant early escalation or switch of SITs and/or alternative therapies such as fecal microbiota transplantation. Among 879 patients, 60% were male and 93% white. Treatment regimens included anti-PD-1 / L1 (43.9%), anti-CTLA-4 (16.5%) and combined therapy (39.6%). Significant factors associated with refractoriness to SIT included: combined ICI regimen (OR:1.7 CI:1.2-2.4, p=0.001), concurrent gastrointestinal AEs (OR:2.1 CI:1.4-3.4, p=0.001), diarrhea CTCAE grade ≥ 2 (OR:3.4 CI: 1.8-6.5, p < 0.0001) and colitis CTCAE grade ≥ 2 (OR:6.5 CI:4.2-10, p < 0.0001), longer steroid duration (OR:1.02 CI:1.0-1.03, p=0.014), multiple steroid tapers attempts (OR:1.7 CI:1.4-2.0, p < 0.0001), initial use IFX (OR:2.3 CI:1.5-3.3, p < 0.0001), ulcerative features on colonoscopy (OR: 1.7 CI:1.1-2.5, p=0.006), acute..."

Checkpoint inhibition • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Oncology

Safety and Predictors of Recurrence in Immune Checkpoint Inhibitor Rechallenge Post-Immune-Mediated Diarrhea and Colitis (ACG 2025) - "Three patients received front-line fecal microbiota transplantation, all with grade > 2 diarrhea or colitis; no recurrences occurred... Of 1128 patients, 58.6% were male and 89.8% white. While 94 patients continued ICI during IMDC, 1026 discontinued; of these, 309 (30.1%) were later rechallenged after a median of 113 days, with recurrence in 98 (31.7%). IMDC management prior to rechallenge involved corticosteroids alone in 89 patients (CTCAE grade > 2 diarrhea and colitis in 74.1% and 43.8%, respectively, recurrence in 20.2%)."

Checkpoint inhibition • Clinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Oncology

The microbiome in cancer. (PubMed, Imeta) - "Finally, advances in microbiome-targeted strategies, such as probiotics, fecal microbiota transplantation, and engineered microbes offer new avenues for adjunctive cancer therapy. This review provides a roadmap for future investigation and underscores the transformative promise of microbiome modulation in cancer prevention and treatment."

Journal • Review • Oncology • Transplantation

A Study of Microbiome Transplantation for the Treatment of Constipation and/or Significant Bloating in Patients With Systemic Sclerosis (clinicaltrials.gov) - P2 | N=21 | Recruiting | Sponsor: The University of Texas Health Science Center, Houston | Not yet recruiting ➔ Recruiting | Trial completion date: Sep 2025 ➔ Sep 2026 | Trial primary completion date: Jun 2025 ➔ May 2026

Enrollment open • Trial completion date • Trial primary completion date • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology • Scleroderma • Systemic Sclerosis • Transplantation

Microbiota-based therapies as novel targets for autism spectrum disorder: A systematic review and meta-analysis. (PubMed, Prog Neuropsychopharmacol Biol Psychiatry) - "Our findings support the potential of microbiota-based therapies as a promising and well-tolerated strategy for improving behavioral symptoms in individuals with ASD. FMT and multi-strain probiotic formulations appear particularly effective. Nevertheless, further high-quality randomized controlled trials-especially involving FMT-are urgently needed to validate these results and guide clinical implementation. Thus, these findings provide a critical foundation for future investigations seeking to refine microbiota-based interventions and uncover the underlying mechanisms through which they influence ASD-related behaviors."

Journal • Retrospective data • Review • Autism Spectrum Disorder • CNS Disorders • Gastrointestinal Disorder • Genetic Disorders • Transplantation

EVALUATING THE ROLE OF PANCREATIC ENZYME REPLACEMENT THERAPY(PERT) IN ICI INDUCED DIARRHEA MANGEMENT (DDW 2025) - "Other regimens included supportive care with steroids, SIT, PERT, and mesalamine in 32 patients (9.8%), while fecal microbiota transplantation (FMT) was performed in 20 patients (6.1%)... Out of 328 patients included, 239 (72.9%) were presented with symptoms suspected of GI toxicity. Treatment varied among these patients: 33 (10.0%) were treated with PERT only, and 37 (11.3%) received steroids only. The predominant approach combined supportive care with steroids, mesalamine, and selective intestinal therapy (SIT), administered to 154 patients (47.0%)."

IO biomarker • Diabetes • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology

Fecal Microbiota Transplantation Reduces Systemic Inflammation and Improves Behavior in Adult Mice with a History of Neonatal Hypoxic-Ischemia (PAS 2025) - No abstract available

Preclinical • Cardiovascular • Inflammation • Transplantation

A Study of Microbiome Transplantation for the Treatment of Constipation in Patients with Systemic Sclerosis (clinicaltrials.gov) - P2 | N=21 | Not yet recruiting | Sponsor: The University of Texas Health Science Center, Houston

New P2 trial • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology • Scleroderma • Systemic Sclerosis • Transplantation

Safety Evaluation of Fecal Microbiota Transplantation in Severe Alcoholic Hepatitis (clinicaltrials.gov) - P1/2 | N=50 | Recruiting | Sponsor: Prasun Kumar Jalal | Phase classification: P1 ➔ P1/2 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Phase classification • Trial primary completion date • Hepatology • Inflammation • Transplantation

The involvement of the microbiota-gut-brain axis in the pathophysiology of mood disorders and therapeutic implications. (PubMed, Expert Rev Neurother) - "Microbiota-targeted interventions, such as symbiotics, prebiotics, paraprobiotics, and fecal microbiota transplants seem to attenuate the severity of depressive symptoms. The available results must be seen as preliminary and need to be replicated and/or confirmed in larger and independent studies, also considering the pathophysiological and clinical heterogeneity of mood disorders."

Journal • Review • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry • Transplantation

A Retrospective Study of Treatment Options for Checkpoint-Inhibitor Colitis and Their Impact on Disease Outcomes (ACG 2024) - "Selective immunosuppressive therapy (SIT) and fecal microbiota transplantation (FMT) are two especially popular treatment options. A total of 1,152 patients met the study criteria, 465 (40.4%) received SIT (177 infliximab, 258 vedolizumab) alone and 62 (5.4%) received FMT. The majority of patients present with grade 2 and above diarrhea or colitis with positive stool biomarkers (lactoferrin and calprotectin). Around 80% of cases required ICI discontinuation, with around 35% of patients able to resume immunotherapy."

Checkpoint inhibition • IO biomarker • Retrospective data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology

Gastrointestinal Infection Prior to Immune Checkpoint Inhibition Hinders Treatment Efficacy and Increases the Risk for Checkpoint-Inhibitor Colitis (ACG 2024) - "Treatments used in both groups did not differ significantly, with the exception of fecal microbiota transplantation (FMT), which was used more in the prior infection group (p=0.029)... 1,132 patients met the study criteria and were included, 34 of whom had a history of GI infection prior to ICI. GI infections were most commonly caused by Clostridiodes difficile and treated with oral antibiotics for a median of 10 days (IQR: 7-14 days). The incidence of IMC was increased within this subgroup, with 8.7% (34/393) of patients with prior GI infection developing colitis compared to 5.1% (1098/21,736) of those without (p=0.002)."

Checkpoint inhibition • Clinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Oncology

Inflammation mediated by gut microbiome alterations promotes lung cancer development and an immunosuppressed tumor microenvironment. (PubMed, Cancer Immunol Res) - "Here, we investigated the role of gut microbiome changes in LUAD development using fecal microbiota transfer and delineated a pathway by which gut microbiome alterations incurred by loss of Lcn2 fostered the proliferation of pro-inflammatory bacteria of the genus Alistipes, triggering gut inflammation...Corroborating our preclinical findings, we found that patients with LUAD with a higher relative abundance of Alistipes species in the gut showed diminished response to neoadjuvant immunotherapy. These insights reveal the role of microbiome-induced inflammation in LUAD and present new potential targets for interception and therapy."

Biomarker • Journal • Tumor microenvironment • Inflammatory Bowel Disease • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL6

Safety Evaluation of Fecal Microbiota Transplantation in Severe Alcoholic Hepatitis (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Prasun Kumar Jalal | Trial completion date: Jul 2024 ➔ Jun 2025 | Trial primary completion date: Jul 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date • Hepatology • Inflammation • Transplantation

Microbiota restoration therapies for recurrent Clostridioides difficile infection reach an important new milestone. (PubMed, Therap Adv Gastroenterol) - "PubMed was reviewed on 1 October 2023, for all papers published concerning the current Food and Drug Administration allowance of the use of fecal microbiota transplantation (FMT) and the studies that led to the licensure of RBX2660 (REBYOTA™), generic name, fecal microbiota, live-jslm, and SER-109 (VOWST™), generic name, fecal microbiota spores, live-brpk. With the licensure of two novel LBPs, we are entering a new phase of microbiota replacement therapy. Having standardized manufacturing and proper monitoring of products, harnessing the microbiome to control and prevent disease has a new beginning."

Journal • Review • Gastroenterology • Infectious Disease • Transplantation

Outcomes of Budesonide as a Treatment Option for Immune Checkpoint Inhibitor-Related Colitis in Patients with Cancer. (PubMed, Cancers (Basel)) - "Budesonide may be an effective strategy to treat and prevent the recurrence of IMC. The remission rates observed in our analysis with budesonide alone are comparable to systemic corticosteroids. Patients that require an extended duration of steroid exposure and those with moderate to severe colitis may benefit from budesonide given its lower risk of infection and complications. Furthermore, we observe that budesonide may serve as a successful bridge from systemic corticosteroids with subsequent biologic treatment. Larger prospective studies are necessary to determine the role of budesonide as well as its safety profile."

Checkpoint inhibition • Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Melanoma • Oncology • Solid Tumor • Transplantation

A Prospective, Randomized, Placebo-Controlled Pilot Study to Characterize the Intestinal Microbiome and to Evaluate the Safety and Fecal Microbiome Changes Following Administration of Lyophilized PRIM-DJ2727 or Placebo Given Orally in Subjects With Nonalcoholic Fatty Liver Disease (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: The University of Texas Health Science Center, Houston | N=12 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Diabetes • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

Study to Evaluate the Fecal Microbiota Transplantation (FMT) in the Treatment of Ulcerative Colitis (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: The University of Texas Health Science Center, Houston | Not yet recruiting ➔ Recruiting

Enrollment open • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Transplantation • Ulcerative Colitis

Rejuvenating fecal microbiota transplant enhances peripheral nerve repair in aged mice by modulating endoneurial inflammation. (PubMed, Exp Neurol) - "Ultimately, restoring a youthful gut microbiome in aged mice led to improved nerve repair and enhanced functional recovery after PNI. Considering that FMT is already a clinically available technique, exploring novel translational strategies targeting the gut microbiome to enhance nerve repair in the elderly seems promising and warrants further evaluation."

Journal • Preclinical • Inflammation • Transplantation • CLDN1 • IL10 • TNFA

Evaluation the Safety and Efficacy of Lyophilized Fecal Microbiota Transplantation Administered Orally for Prevention of Relapse or Intestinal Inflammation in Adults With Ulcerative Colitis (clinicaltrials.gov) - P2 | N=58 | Recruiting | Sponsor: The University of Texas Health Science Center, Houston | Phase classification: P2a ➔ P2 | Trial completion date: Dec 2023 ➔ Dec 2025 | Trial primary completion date: Dec 2023 ➔ Dec 2025

Combination therapy • Phase classification • Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Transplantation • Ulcerative Colitis

Study to Evaluate the Fecal Microbiota Transplantation (FMT) in the Treatment of Ulcerative Colitis (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: The University of Texas Health Science Center, Houston | Trial completion date: Apr 2027 ➔ Dec 2027 | Initiation date: Jun 2023 ➔ Dec 2023 | Trial primary completion date: Apr 2026 ➔ Dec 2026

Trial completion date • Trial initiation date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Transplantation • Ulcerative Colitis

Unraveling the Gut-Brain Axis in Multiple Sclerosis: Exploring Dysbiosis, Oxidative Stress, and Therapeutic Insights. (PubMed, Cureus) - "This review also discusses promising therapeutic interventions, such as fecal microbiota transplantation, probiotics, dietary adjustments, and gut-derived metabolites that offer potential avenues for managing MS. It underscores the need for ongoing research to fully unravel the complexities of the role of the gut-brain axis in MS. Ultimately, this article provides a comprehensive exploration of the topic, offering hope for novel preventive and therapeutic strategies that could significantly improve the lives of individuals affected by this challenging autoimmune condition."

Journal • Review • CNS Disorders • Immunology • Multiple Sclerosis • Transplantation

Colon Adenoma After Diagnosis of Immune Checkpoint Inhibitor-mediated Colitis. (PubMed, J Cancer) - "Four patients received fecal microbiota transplantation... At a median follow up of 12 months after their initial colitis diagnosis, 51.2% of the patients had new incidence of colonic polyps, including a third with adenoma, at a significantly higher incidence than the control group without colitis. Studies with larger sample sizes are needed to further define the long-term impact of colitis and its treatments on colon health and to refine recommendations for surveillance of colonic adenomas and colorectal cancer."

Checkpoint inhibition • Journal • Colonic Polyps • Colorectal Cancer • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Immunology • Melanoma • Oncology • Solid Tumor • Transplantation

Safety Evaluation of Fecal Microbiota Transplantation in Severe Alcoholic Hepatitis (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Prasun Kumar Jalal | Trial completion date: Jul 2023 ➔ Jul 2024 | Trial primary completion date: Jul 2023 ➔ Jul 2024

Trial completion date • Trial primary completion date • Hepatology • Inflammation • Transplantation

Elevated Amyloid-β and Tau Levels in the Brain are Associated with a Reduced Abundance of Neuroprotective Gut Bacteria (AAIC 2023) - "Animal studies have shown that fecal microbiota transplantation reduces amyloid plaques in mouse AD models... We showed that elevated measures of Aβ-PET and tau-PET in the rhinal and the inferior temporal cortex are associated with a reduced abundance of butyrate-producing Butyricicoccus and Ruminococcus in the gut of middle-aged individuals from the FHS. As these bacteria harbor neuroprotective effects, further studies are needed to elucidate underlying mechanisms and assess their therapeutic potential."

Alzheimer's Disease • Transplantation