Serendipity in Refractory Celiac Disease: Full Recovery of Duodenal Villi and Clinical Symptoms after Fecal Microbiota Transfer Original paper
Researched by:
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Karen Pendergrass
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Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
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Autoimmune Diseases
Autoimmune Diseases
Autoimmune disease is when the immune system mistakenly attacks the body's tissues, often linked to imbalances in the microbiome, which can disrupt immune regulation and contribute to disease development.
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Karen Pendergrass
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
What was studied?
This study examined the impact of fecal microbiota transfer (FMT) on a patient with refractory celiac disease type II (RCD II). The patient initially received FMT as treatment for recurrent Clostridium difficile infection (CDI), but the intervention unexpectedly resulted in full recovery of duodenal villi and resolution of celiac symptoms, suggesting a potential therapeutic role for microbiome manipulation in RCD II.
Who was studied?
A 68-year-old woman with a 10-year history of RCD II was the subject of this study. Despite adherence to a strict gluten-free diet, she experienced persistent villous atrophy and malabsorption. She had been receiving budesonide therapy and later underwent cladribine treatment, neither of which alleviated her condition. The patient was repeatedly hospitalized due to severe diarrhea, dehydration, and infections, and was ultimately treated with FMT for recurrent CDI.
What were the most important findings?
FMT not only resolved the patient’s CDI but also led to complete histological recovery of the duodenal mucosa. Before FMT, duodenal biopsies confirmed villous atrophy (Marsh IIIA) and an abnormal intraepithelial lymphocyte population (>80%). However, post-FMT, the patient experienced significant clinical improvement, gaining weight and becoming symptom-free. Follow-up biopsies at six months showed full villous recovery (Marsh 0), although 71% of intraepithelial lymphocytes remained aberrant.
Microbiome analysis of the FMT donor revealed a high Shannon diversity index (3.81), suggesting a diverse and resilient microbial community. Unfortunately, due to the lack of a pre-FMT stool sample from the patient, a direct comparison of microbiome shifts could not be conducted. However, the resolution of symptoms and histological improvement strongly indicate that microbiome alterations played a role in disease modulation. Given previous studies implicating gut dysbiosis in celiac disease pathogenesis, this case highlights a possible causal role of microbiota in maintaining the chronic inflammatory state of RCD II.
What are the greatest implications of this study?
This study provides compelling evidence that microbiome manipulation may be a viable therapeutic strategy for RCD II, a condition with limited treatment options and high mortality risk. The findings suggest that gut dysbiosis could be a key driver of persistent villous atrophy in RCD II and that FMT may help restore intestinal homeostasis. If confirmed in larger studies, this could shift the treatment paradigm for RCD II, potentially offering an alternative to immunosuppressive therapies or autologous stem cell transplantation. Given the poor prognosis associated with RCD II, the ability to restore mucosal integrity through microbiome-targeted interventions represents a significant advancement. Further research should explore optimal donor selection, microbial composition, and long-term effects of FMT in RCD II patients.
Fecal Microbiota Transplantation (FMT)
Fecal Microbiota Transplantation (FMT) involves transferring fecal bacteria from a healthy donor to a patient to restore microbiome balance.