IMPACTT Symposium 2026 Abstracts

Anikka Swaby (Poster #63) MD/PhD Candidate, Rosalind & Morris Goodman Cancer Institute, McGill University | Canada

Leveraging Diet-Tunable Gut Microbial Function to Enhance Checkpoint Blockade in Lung Cancer

Anikka Swaby [1,2], Edmond Rafie [3,4], Samuel Doré [1,5], Lysanne Desharnais [1], Aline Atallah [1,2], Juliette Wilson-Sanchez [1,2], Valérie Breton [1], Benoit Fiset [1], Bertrand Routy [3,4], Logan Walsh [1,5], Arielle Elkrief [3,4] and Daniela F. Quail [1,2,6]  

1. Rosalind & Morris Goodman Cancer Institute, Montreal, Canada; 
2. Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, Canada; 
3. Research Centre of the Centre Hospitalier de l’Université de Montréal, Montreal, Canada
4. Hematology-Oncology Division, Department of Medicine, Centre Hospitalier de l’Université de Montréal, Montreal, Canada;
5. Department of Human Genetics, McGill University, Montreal, Canada;
6. Department of Physiology, McGill University, Montreal, Canada

Immune checkpoint inhibitors (ICIs) have transformed lung cancer treatment, yet benefit only a minority of patients. High body mass index and the gut microbiome are independently associated with ICI efficacy, but their mechanistic connection remains unclear. We recently demonstrated that short-term exposure to a high-fat obesogenic diet augments ICI efficacy in a microbiome-dependent manner. However, this was not a universal effect of all high-fat diets, suggesting the composition, not quantity, of dietary fat influences ICI efficacy. Here we hypothesized that specific sources of dietary fats remodel gut microbial function to shape ICI responses. Using diet surveys in a prospective cohort of NSCLC patients treated with ICI, we found higher intake of specific dietary lipids was associated with prolonged progression-free survival, with oleic acid ranking highest among 97 nutrient exposures. To explore this in vivo, we designed a panel of nine nutrient-matched high-fat diets differing only in fat source, combined with a transplantable lung cancer model to assess αPD-1 response. Intriguingly, two oleic acid-rich diets produced divergent effects; avocado oil promoted strong αPD-1 response whereas olive oil did not, suggesting factors beyond total oleic acid content may be required to “license” its beneficial effects on ICI efficacy. Metagenomic, metabolomic and lipidomic profiling revealed that avocado oil enriched specific taxa (Akkermansia muciniphila, Lactobacillus johnsonii) and altered microbial metabolism, lipid processing and metabolite bioavailability. Functionally, antibiotic treatment abolished the beneficial effect of avocado oil, confirming a microbiome-dependent effect. Consistently, FMT from avocado oil donors into olive oil recipients transferred αPD-1 sensitivity, despite recipient continuation of the non-responder olive oil diet, suggesting the licensing effect is mediated at the level of microbiome remodeling. Together, our findings identify dietary lipid composition, rather than fat quantity alone, as a determinant of microbiome-dependent responses to immune checkpoint blockade, providing insights into dietary and microbiome-informed interventions.

Ayesha Wijesinghe (Poster #24) PhD Student, University of Calgary | Canada

Gut microbiome regulates neutrophil immunometabolism

Ayesha Wijesinghe1,2, Nicole A Cho1,2, Jared Schlechte1,2, Ian-ling Yu1,2, Oscar Tejada1,2, and Braedon McDonald1,2

1Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary
2Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary

Background:
Commensal gut microbes play essential roles in neutrophil development and functional maturation, yet their influence on cellular bioenergetics is poorly understood. We hypothesized that microbiota-derived signals contribute to regulating metabolism in neutrophils, and that microbiome absence in GF mice, or human-disease associated dysbiosis may impair cellular energetics in neutrophils, leading to compromised neutrophil antimicrobial activity.
Methods:
We assessed neutrophil immunometabolic function in 4 murine models under baseline/naïve conditions and following systemic infection with E. coli: specific-pathogen-free (SPF) versus germ-free (GF) mice, and humanized microbiome–associated (HMA) mice engrafted with fecal microbiome from healthy donors or critically ill patients with dysbiosis. Mitochondrial (oxidative phosphorylation) and glycolytic ATP production rates were quantified by Seahorse XF assays, and mitochondrial biomass, membrane potential, and reactive oxygen species (mitoROS) generation were quantified by flow cytometry. Neutrophil antimicrobial functions (phagocytosis oxidative bursts, and NETs) were measured by flow cytometry and imaging.
Results:
Neutrophils from GF mice exhibited a significant reduction in both mitochondrial (OXPHOS) as well as glycolytic ATP production compared to SPF controls, coupled with lower total cellular mitochondrial biomass, inner membrane potential, and mitoROS production compared to SPF. Metabolic impairment in GF neutrophils was accompanied impaired antimicrobial effector functions, including reduced phagocytosis and oxidative burst in response to bacterial challenge. Pharmacological inhibition of OXPHOS (oligomycin + Rot/AA) further exacerbated these functional defects, whereas pharmacological potentiation of mitochondrial function (elamipretide) significantly rescued antimicrobial functions in GF neutrophils. Neutrophils from
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mice colonized with human dysbiotic microbiota from critically ill patients exhibited significantly lower mitochondrial ATP production coupled with functional impairment compared to neutrophils from mice with healthy human donor microbiota.
Conclusions:
The gut microbiota is a crucial regulator of neutrophil immunometabolism, supporting neutrophil mitochondrial oxidative phosphorylation which is critical for powering antimicrobial effector functions.

Caydin Cleland (Poster #19) Master’s Student, University of Calgary | Canada

Engineering Contact-Dependent Inhibition in E. coli Nissle 1917 for Selective Targeting of Uropathogenic E. coli

Caydin Cleland, and Xiaofan Jin.

Recurrent urinary tract infections are commonly caused by uropathogenic Escherichia coli (UPEC), which can persist in the intestinal reservoir and later seed new urinary infections. Current treatment strategies often rely on repeated antibiotics, which can select for antimicrobial resistance and disrupt beneficial gut communities. Microbiome-sparing approaches are therefore needed to selectively reduce UPEC while preserving commensals.

We address this need by engineering the probiotic strain E. coli Nissle 1917 (EcN) as a targeted living antimicrobial against UPEC. Our approach leverages EcN’s contact-dependent inhibition (CDI) system, a bacterial competition mechanism in which an inhibitor cell delivers a toxin to a target cell upon direct contact. The CDI system is encoded by cdiBAI: cdiB encodes an outer-membrane transporter required for cdiA export, cdiA encodes the toxin-delivery protein, and cdiI encodes immunity. However, EcN CDI is predicted to be inactive due to a premature stop codon in cdiB.

We hypothesize that activating EcN CDI will enable selective inhibition of UPEC strains such as UTI89 while limiting off-target effects on commensal bacteria. To test this, we are using plasmid-based expression of a corrected cdiBAI operon and chromosomal correction of the cdiB premature stop codon. CDI-active and CDI-inactive strains will be compared with UTI89 using colony-forming unit counts, fluorescence monitoring, and competitive index calculations. Selectivity will be assessed using individual strains from the defined Oligo-MM12 mouse gut consortium.

Preliminary bioinformatic analysis supports UTI89 as a rational target, as EcN and UTI89 cdiA proteins show strong similarity, including complete identity in the receptor-binding domain. We have built the CDI plasmid, introduced it into laboratory E. coli strains, and observed inhibition. Ongoing work will test CDI activity in EcN against UPEC targets. This work advances a microbiome-sparing strategy for recurrent UTI prevention and supports engineered probiotics as precision antimicrobials that suppress pathogen reservoirs without disrupting commensal communities.

Dr. Fernando Suarez-Sanchez (Poster #35) Associate Researcher, Mexican Social Security Institute | Mexico

A Coprococcus species is associated with BMI in patients undergoing malabsorptive bariatric surgery, and its abundance is influenced by magnesium and thiamin intake.

Fernando Suarez-Sanchez(1), Evelyn Perez-Ruiz(1,2), Claudia Ivonne Ramirez-Silva(3), Mario Antonio Molina-Ayala(4), Sandra Rivera-Gutierrez(5), Lizbel Leon-Solis(5), Lazaro Garcia-Morales(6), Arturo Rodriguez-Gonzalez(4), Cesar Martinez-Ortiz(4), Luis Axiel Meneses-Tapia(5), and Miguel Cruz-Lopez(1)

(1) Medical and Biochemistry Research Unit, Specialty Hospital, National Medical Center, Mexican Social Security Institute, Mexico City, Mexico

(2) Faculty of Chemistry, Dental and Health Sciences, National Autonomous University of Mexico, Mexico City, Mexico

(3) Department of Maternal, Child, and Adolescent Nutrition. Center for Nutrition and Health Research. National Institute of Public Health. Cuernavaca, Morelos, Mexico

(4) Diabetes and Obesity Clinic, Specialty Hospital, National Medical Center, Mexican Social Security Institute, Mexico City, Mexico

(5) Department of Microbiology, National School of Biological Sciences, National Polytechnic Institute, Mexico City, Mexico

(6) Department of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City, Mexico

Title: A Coprococcus species is associated with BMI in patients undergoing malabsorptive bariatric surgery, and its abundance is influenced by magnesium and thiamin intake

Background: Severe obesity is associated with metabolic disturbances and an increased risk of type 2 diabetes. Bariatric surgery, particularly malabsorptive procedures, leads to significant clinical improvements and alters gut microbiota composition. This study aimed to identify bacterial taxa associated with BMI changes in patients undergoing bariatric surgery and to explore their relationship with dietary nutrient intake.

Methods: Patients with severe obesity were evaluated before and after bariatric surgery. Fecal DNA was extracted, and the V4 region of the 16S rRNA gene was sequenced. Data processing and taxonomic classification were performed using QIIME2 with the Greengenes database. Nutrient intake was assessed using a 7-day dietary recall. Anthropometric measurements and blood samples were collected to evaluate clinical variables. Statistical analyses were conducted using R.

Results: Significant changes in gut microbiota diversity were observed after surgery. Shannon and Simpson indices decreased significantly (p < 0.001), and beta diversity analyses showed clear differences between pre- and post-surgery samples (p = 0.001). A Coprococcus species was positively correlated with magnesium and thiamin intake in post-surgery patients (rho = 0.816 and 0.812; pFDR = 0.029). Its abundance was positively associated with BMI before surgery (p = 0.043) but negatively associated after surgery (p = 0.036). Taxa within Clostridiales and pathways related to sugar degradation and production of acetate, thiamin, and amino acids were enriched before surgery.

Conclusions: A Coprococcus species showed opposite associations with BMI before and after surgery and correlated positively with magnesium and thiamin intake. Optimizing micronutrient intake may enhance bariatric surgery outcomes by modulating gut microbiota.

Dr. Xu Zhang (Poster #37) Research Scientist, Health Canada | Canada

Dissecting functional dynamics of fecal-derived in vitro stable microbial communities

Angela Wang, Emily Fekete, Marybeth Creskey; Health Canada, Ottawa ON, Canada;

Zhibin Ning, Janice Mayne; University of Ottawa, Ottawa ON, Canada;

Daniel Figeys; Quadram Institute Bioscience, Norwich Research Park, Norwich, Norfolk, UK;

Xuguang Li, Xu Zhang; Health Canada, Ottawa ON, Canada

Fecal microbiota transplantation (FMT) is a regulatory-approved therapy for preventing recurrent Clostridioides difficile infection and has been widely evaluated in clinical trials for other indications as well, including inflammatory bowel disease, cancer, and neurodegenerative disorders. However, significant challenges exist for FMT due to the safety risks and limited scalability for drug product manufacture. As an alternative, fecal derived stable in vitro microbial communities are being explored to balance the maintenance of microbial diversity with the ability to achieve well-controlled drug quality. We generated in vitro microbial communities with human stool biobank samples across multiple donors and cultured in different microbiome growth media. The microbial growth was monitored over 25 passages, and the microbiome samples were analyzed using quantitative metaproteomics. The results showed that the establishment of stable in vitro fecal microbial communities is determined by the combined effects of donor microbiome and the culture medium, whereas initial and passaging Inoculation rates display minimal influences. Both the taxonomic and functional profiles of these stable communities vary in a donor- and medium-dependent manner, with the culture medium having the greatest impact on shaping the microbiome compositions. Taxon-specific functional analysis using metaproteomics enables the attribution of specific microbial activities to specific microbial species and available nutrients across different culture media, particularly carbohydrates such as mucin O-glycans. These factors collectively contribute to the establishment of stable microbial communities that vary in their distances to uncultured natural human fecal microbiomes. In conclusion, our study demonstrates the feasibility of generating stable and reproducible in vitro human gut microbial communities as microbiome models and potential alternatives to FMT. By using an operational taxon-function framework of metaproteomics, this study identifies factors that govern the community establishment, supporting future optimization and application of fecal-derived in vitro microbiomes.