Understanding Fecal Microbiota Transplantation: The 'Poop Pills' Innovation

Fecal Microbiota Transplantation (FMT), often referred to colloquially as 'poop pills' due to their encapsulated form, involves transferring healthy gut bacteria from screened donors into patients to restore microbiome balance. At Western University in London, Ontario, researchers have pioneered oral capsules known as LND101, made from donor stool processed in labs at the Lawson Research Institute. This method bypasses invasive procedures like colonoscopy, making it patient-friendly and scalable.

The process starts with rigorous donor screening for pathogens, followed by stool homogenization, filtration, and encapsulation into 36-40 capsules per full dose. Patients ingest them after bowel preparation, typically receiving one full dose and two half-doses spaced weeks apart. This restores alpha diversity in the gut microbiome, crucial for modulating immune responses in cancer treatment.

In the context of immunotherapy—drugs like anti-PD-1 (e.g., pembrolizumab, nivolumab) and anti-CTLA-4 (e.g., ipilimumab) that unleash T-cells against tumors—dysbiotic microbiomes can hinder efficacy or cause severe immune-related adverse events (irAEs) like colitis. FMT addresses this by eliminating harmful bacteria such as Segatella copri or Enterocloster citroniae, promoting anti-inflammatory taxa like Faecalibacterium prausnitzii.

Groundbreaking Clinical Trials Led by Western University Researchers

Two pivotal studies published January 28, 2026, in Nature Medicine highlight FMT's potential. The Phase 1 PERFORM trial (NCT04163289) at London Health Sciences Centre tested LND101 with immunotherapy in 20 treatment-naïve metastatic renal cell carcinoma (mRCC) patients. Meanwhile, the Phase 2 FMT-LUMINate trial (NCT04951583) evaluated FMT plus anti-PD-1 in 20 non-small cell lung cancer (NSCLC) patients and dual ICI in 20 melanoma patients, led collaboratively by Western's Saman Maleki, PhD, and Montréal's Arielle Elkrief, MD.

PERFORM focused on safety, combining FMT with ipilimumab/nivolumab (n=16) or pembrolizumab-based regimens. FMT-LUMINate prioritized objective response rates (ORR). These trials underscore Western University's translational research prowess through its Schulich School of Medicine & Dentistry.

Building on earlier work, including 2023 melanoma Phase I trials showing FMT safety, these build momentum for pan-Canadian efforts like Canbiome2.Western News coverage details the collaborations with Lawson and LHSCRI.

Key Findings: Dramatic Improvements in Response Rates

In NSCLC, FMT plus pembrolizumab yielded an 80% ORR (16/20 patients), surpassing the 39-45% typical benchmark, with 95% disease control and 100% one-year overall survival. Melanoma saw 75% ORR (15/20) versus 50-58% standard. For mRCC, 50% ORR (9/18 evaluable), including 11% complete responses, and median progression-free survival of 11.15 months.

• Responders showed higher alpha diversity post-FMT and durable engraftment of donor strains.
• Loss of baseline deleterious bacteria (e.g., Clostridium innocuum) correlated with efficacy, validated in mouse models.
• Anti-inflammatory metabolites like vitamin A and L-histidine preserved in responders.

These results position FMT as a microbiome modulator enhancing T-cell infiltration and reducing resistance.PERFORM trial paper

Western University's Leadership in Microbiome-Oncology Research

Saman Maleki Vareki, PhD, Associate Professor in Oncology, Pathology, and Medical Biophysics at Western's Schulich School, leads the Maleki Lab at London Regional Cancer Program. Named 2024 Researcher of the Year by Schulich, Maleki's team integrates clinician-scientists for tumor-agnostic immuno-oncology trials spanning melanoma, lung, kidney, pancreatic, and breast cancers.

Collaborators like Michael Silverman, MD (Infectious Diseases Chair), Ricardo Fernandes, MD (Oncology), and Seema Nair Parvathy, PhD, developed LND101 capsules. Funded by CIHR, OICR, and foundations, Western positions London as a global FMT hub. For aspiring researchers, opportunities abound in such cutting-edge labs—check AcademicJobs.com/research-jobs for similar roles in Canada.

This work exemplifies how Canadian universities drive precision medicine, attracting talent nationwide.

Mechanisms: How Gut Microbiome Influences Cancer Immunotherapy

The gut microbiome shapes systemic immunity via metabolites and bacterial signals. Cancer patients often have dysbiosis, enriching pro-tumor bacteria that promote PD-1 resistance or irAEs. FMT depletes these (e.g., Segatella copri linked to inflammation) while enriching beneficial ones, boosting CD8+ T-cells and regulatory T-cells (Tregs).

1. Donor stool processed into capsules.
2. Patient ingests, achieving engraftment.
3. Microbiome remodels, reducing kynurenine (immunosuppressive) and elevating anti-tumor signals.
4. Enhanced ICI efficacy via TILs (tumor-infiltrating lymphocytes).

Mouse models confirmed: reintroducing lost bacteria abrogates benefits. Western's metagenomic analyses (MetaPhlAn, StrainPhlAn) pinpointed these dynamics.FMT-LUMINate details

Safety and Quality of Life Benefits

Safety was exemplary: no FMT-attributable grade 4/5 events in PERFORM; NSCLC had zero grade 3+ irAEs, versus 50% grade 3 in mRCC (expected for ICIs). Melanoma saw 65% grade 3+ but manageable. Quality of life remained stable (EQ-5D-5L), contrasting toxicity-burdened controls.

• Reduced colitis/diarrhea, enabling treatment completion.
• Lower pro-inflammatory enzymes (e.g., EC 2.6.1.42).
• Preserved protective metabolites like stearoylcarnitine.

Maleki notes: "Reducing toxic side effects will be a gamechanger." For patients, this means enduring therapy longer.

Challenges, Limitations, and Broader Impacts

Challenges include donor variability—Prevotella-rich donors increased melanoma toxicities—and small Phase 1/2 samples (n=20/cohort). Strain-level tracking shows transient engraftment in non-responders. Scalability via LND101 addresses this.

In Canada, where cancer affects 2 in 5, FMT could transform care, especially for immunotherapy non-responders (50%+). Western's work influences policy, with CIHR backing larger RCTs like Canbiome2. Stakeholder views: Patients report tolerability; oncologists hail reduced dropouts.

Explore careers advancing such research at AcademicJobs.com/higher-ed-jobs/research-assistant-jobs.

Expert Quotes and Perspectives

"FMT opens personalized microbiome therapies," says Elkrief. Fernandes adds: "Help people live longer with fewer side effects." Silverman emphasizes collaboration: "Lawson-LHSC innovation scales to thousands."

Balanced views note need for Phase 3 validation, but optimism prevails. Jamal: "Teamwork translates discoveries to impact."

Photo by Hermes Rivera on Unsplash

Future Outlook: From Trials to Standard Care

Ongoing: Pancreatic (NCT03772899), breast trials; Canbiome2 RCT. By 2030, FMT could integrate routinely, per OICR visions. Western recruits postdocs—visit AcademicJobs.com/higher-ed-jobs/postdoc.

Actionable: Patients inquire via LHSC; researchers collaborate. Rate profs like Maleki at RateMyProfessor. Career advice at higher-ed-career-advice.

This Canadian breakthrough signals microbiome era in oncology.