Irritable Bowel Syndrome and Nickel Allergy:What Is the Role of the Low Nickel Diet? 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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Irritable Bowel Syndrome (IBS)
Irritable Bowel Syndrome (IBS)
Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder characterized by symptoms such as abdominal pain, bloating, and altered bowel habits. Recent research has focused on the gut microbiota's role in IBS, aiming to identify specific microbial signatures associated with the condition.
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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 pilot study evaluated the prevalence of nickel (Ni) allergy in individuals diagnosed with irritable bowel syndrome (IBS) and investigated the clinical efficacy of a low-nickel diet (LNiD) in this population. Specifically, the authors assessed the impact of the dietary intervention on gastrointestinal symptoms, intestinal permeability, quality of life, and psychological status in Ni-sensitized IBS patients. It also analyzed how the severity of allergic skin reactions and IBS subtypes might influence changes in gut permeability during LNiD intervention.
Who was studied?
Twenty patients fulfilling Rome III criteria for IBS and exhibiting Ni sensitization (confirmed by positive patch test) were enrolled. These individuals had undergone a thorough exclusion process to rule out other organic gastrointestinal disorders, infections, or metabolic dysfunctions. The sample predominantly consisted of females, with most presenting the diarrhea-predominant (IBS-D) subtype. After baseline evaluation of intestinal permeability, psychological wellbeing, and gastrointestinal symptoms, participants followed a low-Ni diet for three months. Compliance was monitored via dietary diaries. Post-intervention assessments included repeated clinical questionnaires and permeability testing using ⁵¹Cr-EDTA for patients with initially elevated intestinal permeability. A control group of healthy subjects matched by age, sex, and socioeconomic background was included for comparison in permeability analysis.
What were the most important findings?
A strikingly high prevalence of nickel allergy was found among IBS patients, particularly in females. The LNiD significantly alleviated gastrointestinal symptoms (except vomiting) and improved general well-being scores (notably bodily pain and physical functioning). Despite improvements in symptoms, all participants continued to show elevated intestinal permeability post-intervention, suggesting persistent barrier dysfunction possibly due to chronic mucosal immune activation. Interestingly, intestinal permeability changes (Δ⁵¹Cr-EDTA) varied by IBS subtype and allergic response severity. Patients with stronger Ni skin reactivity (++/+++) were more likely to experience worsened barrier function, while those with IBS-M or IBS-U subtypes exhibited improvement. Psychometric testing revealed widespread psychological distress, especially anxiety, supporting the established association between IBS and affective dysregulation. These findings reinforce the concept of systemic nickel allergy syndrome (SNAS) as a relevant comorbidity in IBS and point toward immune-mediated mechanisms involving CD4+ T cell infiltration and Th2 cytokines as underlying contributors to both gastrointestinal and systemic symptoms.
From a microbiome perspective, although the study did not directly assess microbial composition, its findings implicate Ni-induced barrier dysfunction as a potential facilitator of microbial dysbiosis. The interplay between metal exposure, gut immune activation, and barrier integrity represents a critical axis in microbiome-host interaction and warrants further microbial profiling in future studies.
What are the greatest implications of this study?
This study identifies a potentially overlooked driver of IBS symptoms—nickel hypersensitivity—and provides preliminary but compelling evidence for dietary nickel restriction as a therapeutic intervention in select IBS patients. Its implications extend to redefining subgroups within IBS, informing personalized nutrition strategies, and advancing the study of metal-induced gut dysfunction as a contributor to microbial dysbiosis. Moreover, it highlights the need for integrative care models that address metal exposure, gut permeability, immune status, and psychological health concurrently. Given that low-Ni diets do not restrict FODMAPs, this study also challenges prevailing dietary paradigms in IBS management by introducing a non-FODMAP, immune-targeted approach with mechanistic plausibility.