Washed Microbiota Transplantation for the Treatment of Recurrent Fungal Infection in a Patient with Ulcerative Colitis
Ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), often requires long-term immunosuppressive therapies, which predispose patients to opportunistic infections, including invasive fungal infections. Managing such complications is challenging, as prolonged antifungal use disrupts microbial balance, exacerbates dysbiosis, and can worsen colitis. This case report highlights the successful application of washed microbiota transplantation (WMT), a refined fecal microbiota transplantation (FMT) methodology, combined with immunosuppressive therapy to address recurrent Candida glabrata infection in a patient with refractory UC, underscoring the interplay between gut mycobiota, host immunity, and therapeutic innovation.
Patient Background and Clinical Challenges
A 31-year-old male presented with a 20-year history of UC and psoriasis, diagnosed in 2007. His treatment included 5-aminosalicylic acid, corticosteroids, and anti-tumor necrosis factor (TNF) antibodies, but these provided only transient relief. Over time, he developed steroid dependence and secondary loss of response to anti-TNF therapy. By March 2018, cyclosporine was initiated to manage worsening UC and pustular psoriasis, leading to temporary improvement. However, by July 2018, he experienced severe relapse, with diarrhea (10–15 episodes/day), and tested positive for fungal biomarkers (glucan and galactomannan) in stool. Despite prolonged antifungal regimens (intravenous/oral itraconazole for 5 months, fluconazole for 6 months, and voriconazole for 1 month), C. glabrata persisted in blood and stool cultures, accompanied by septic shock and drug-induced liver injury.
Admission Findings and Diagnostic Complexity
Upon transfer to the authors’ institution, laboratory results revealed systemic inflammation: leukocytosis (16.5 × 10⁹/L), neutrophilia (89.5%), elevated C-reactive protein (20.7 mg/L), and erythrocyte sedimentation rate (22 mm/h). Hypothalamic-pituitary-adrenal axis suppression was evident with critically low plasma cortisol (<3 µg/mL). Stool cultures confirmed C. glabrata, while Clostridium difficile and bacterial pathogens were absent. Colonoscopy demonstrated pancolitis (Mayo score = 11) with erythema, ulceration, and spontaneous bleeding. Comorbidities included femoral head necrosis, osteoporosis, adrenocortical insufficiency, Hashimoto thyroiditis, and malnutrition, complicating therapeutic options.
Intervention with Washed Microbiota Transplantation (WMT)
WMT, an advanced FMT technique using automated purification to reduce pathogen risks and improve consistency, was selected to restore microbial balance and counteract fungal overgrowth. The protocol adhered to the 2019 consensus by the Fecal Microbiota-standardization Study Group. Five units of washed microbiota suspension from a rigorously screened donor (via China’s fmtBank) were administered via nasojejunal tube, combined with enteral nutrition. Within one week, inflammatory markers (CRP, ESR) normalized, and stool fungal cultures turned negative. However, stool frequency remained elevated (10–15/day), prompting a “step-up” strategy integrating cyclosporine.
Integration of Immunosuppression and Sustained Remission
Cyclosporine was reintroduced post-WMT to suppress immune-driven colonic inflammation, aligning with reported step-up FMT strategies for refractory IBD. Within two weeks, stool frequency dropped to 2/day, with sustained normalization of inflammatory markers. Thalidomide, added for its anti-TNF and mucosal healing properties, was continued post-discharge to maintain remission. Follow-up at 3 and 6 months confirmed absence of C. glabrata in stool cultures, restored liver function, and improved quality of life.
Mechanistic Insights and Clinical Implications
This case illustrates the dual role of WMT in resolving fungal dysbiosis and modulating gut-immune crosstalk. Candida species, particularly C. glabrata, thrive in immunocompromised hosts, exacerbating colitis through pro-inflammatory pathways (e.g., Th17 activation). WMT likely reduced fungal burden by restoring competitive bacterial microbiota, thereby attenuating inflammation. The synergy between WMT and cyclosporine highlights the importance of combining microbial restoration with targeted immunosuppression in refractory cases. Notably, WMT’s rapid effect on fungal clearance contrasts with the delayed action of thalidomide (8–12 weeks), emphasizing the need for staged therapeutic approaches.
Addressing Comorbidities and Therapeutic Nuances
The patient’s clinical complexity—adrenal insufficiency, steroid-induced osteonecrosis, and thyroid dysfunction—precluded corticosteroid reuse. Cyclosporine’s rapid efficacy and favorable safety in acute severe UC made it a rational choice, albeit limited earlier by uncontrolled fungal infection. WMT bridged this gap by eliminating the infectious trigger, enabling safe cyclosporine rechallenge. Furthermore, enteral nutrition optimized mucosal healing and microbiota recovery, synergizing with WMT’s benefits.
Advancing FMT: From Methodology to Mycobiota Modulation
Traditional FMT’s variability in efficacy and safety prompted the evolution toward WMT, which enhances reproducibility by removing fecal debris and concentrating viable microbiota. This case aligns with emerging evidence that FMT/WMT reshapes fungal communities, reducing Candida colonization and associated inflammation. A 2020 study by Leonardi et al. similarly linked FMT-induced fungal shifts to improved colitis outcomes, validating this approach’s mechanistic plausibility.
Conclusion
This report underscores WMT’s potential as a safe and effective adjunct for recurrent fungal infections in immunocompromised UC patients. By restoring microbiota diversity and dampening fungal-driven inflammation, WMT creates a therapeutic window for immunosuppressants to achieve sustained remission. Future studies should explore mycobiota-targeted protocols and larger cohorts to validate WMT’s role in fungal-IBD comorbidities.
doi.org/10.1097/CM9.0000000000001212
Was this helpful?
0 / 0