Irritable Bowel Syndrome-Like Disorders in Endometriosis: Prevalence of Nickel Sensitivity and Effects of a Low-Nickel Diet. An Open-Label Pilot Study. Original paper
Researched by:
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Karen Pendergrass
ID
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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Women’s Health
Women’s Health
Women’s health, a vital aspect of medical science, encompasses various conditions unique to women’s physiological makeup. Historically, women were often excluded from clinical research, leading to a gap in understanding the intricacies of women’s health needs. However, recent advancements have highlighted the significant role that the microbiome plays in these conditions, offering new insights and potential therapies. MicrobiomeSignatures.com is at the forefront of exploring the microbiome signature of each of these conditions to unravel the etiology of these diseases and develop targeted microbiome therapies.
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Endometriosis
Endometriosis
Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (HBOT), Low Nickel Diet, and Metronidazole therapy.
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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 open-label pilot study investigated the prevalence of nickel allergic contact mucositis (Ni ACM) in women with endometriosis who presented with irritable bowel syndrome (IBS)-like symptoms and assessed the efficacy of a low-nickel diet (LNiD) in ameliorating gastrointestinal, extra-intestinal, and gynecological symptoms. The study aimed to determine whether nickel (Ni) sensitivity contributes to the symptom burden in endometriosis and whether dietary nickel restriction can serve as a therapeutic intervention.
Who was studied?
The study initially screened 83 women of reproductive age diagnosed with endometriosis via imaging or laparoscopy who also experienced at least three gastrointestinal symptoms scoring ≥5 on the Gastrointestinal Symptom Rating Scale (GSRS). After applying exclusion criteria (e.g., celiac disease, IgE-mediated food allergies), 47 patients remained eligible. Sixteen dropped out due to the dietary restrictions, leaving 31 who completed the study. Each participant underwent a nickel oral mucosa patch test (omPT) to identify Ni ACM. Of the 31 patients, 28 (90.3%) tested positive. All participants followed a low-Ni diet for three months, with symptoms reassessed using the GSRS at baseline (T0) and after the intervention (T1).
What were the most important findings?
Nickel ACM was highly prevalent among women with endometriosis and IBS-like symptoms, with 90.3% of study completers testing positive via omPT. All patients who adhered to a three-month low-nickel diet experienced statistically significant reductions in all 15 gastrointestinal symptoms, including bloating, abdominal pain, diarrhea, and constipation. Additionally, the LNiD led to meaningful improvements in seven extra-intestinal symptoms such as headache, fatigue, and joint pain, as well as in hallmark gynecological symptoms of endometriosis: chronic pelvic pain, dysmenorrhea, and dyspareunia. These improvements underscore a systemic role of nickel sensitivity in the symptomatology of endometriosis beyond localized pelvic pathology.
From a microbiome perspective, Ni ACM reflects a low-grade inflammatory response that disrupts mucosal immune regulation and intestinal barrier integrity—two key mechanisms implicated in microbial dysbiosis. Though microbiome composition was not directly assessed, the systemic inflammatory profile induced by dietary nickel may favor enrichment of nickel-tolerant pathobionts, including certain Gammaproteobacteria and urease-producing bacteria, while impairing barrier-supporting commensals. This aligns with broader hypotheses on the metallomic drivers of endometriosis-associated dysbiosis.
What are the greatest implications of this study?
This study provides compelling evidence that nickel hypersensitivity may be a clinically significant and previously underrecognized contributor to the gastrointestinal and systemic symptom burden in endometriosis. It positions Ni ACM not only as a comorbidity but as a potential driver of symptom exacerbation, offering a new lens through which to understand IBS-like manifestations in endometriosis. Importantly, the successful use of a targeted dietary intervention based on objective testing (omPT) introduces a personalized medicine framework that could improve quality of life while minimizing unnecessary dietary restrictions, such as those imposed by low-FODMAP diets. If validated in larger, randomized cohorts, the incorporation of nickel testing and dietary counseling into standard endometriosis management could represent a low-risk, high-reward clinical advance.
Endometriosis
Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (HBOT), Low Nickel Diet, and Metronidazole therapy.
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.
Low‑Nickel Diet (LNiD)
A low-nickel diet (LNiD) is a therapeutic dietary intervention that eliminates high-nickel foods, primarily plant-based sources such as legumes, nuts, whole grains, and cocoa, to reduce systemic nickel exposure. It is clinically validated for managing systemic nickel allergy syndrome (SNAS) and nickel-induced eczema. Its relevance is well-established in microbiome modulation, with studies demonstrating clinical benefits in conditions such as endometriosis, fibromyalgia, irritable bowel syndrome, and GERD.
Nickel
Bacteria regulate transition metal levels through complex mechanisms to ensure survival and adaptability, influencing both their physiology and the development of antimicrobial strategies.