Lactose Intolerance and Intestinal Permability

Официальное название

Observational Cross-Sectional Study of Intestinal Permeability in Adults With Lactose Intolerance

Обзор

"This study evaluates the interplay between lactose intolerance, intestinal barrier function (zonulin), and intestinal inflammation (fecal calprotectin) in adults, aiming to clarify their independent contributions to symptom severity and quality of life."

Подробное описание

The gastrointestinal system's barrier functions play a critical role in maintaining intestinal and overall health. Tight junction structures, regulated by zonulin, are key components of this barrier, and elevated zonulin levels can increase intestinal permeability, facilitating translocation of luminal particles into the systemic circulation and promoting inflammation. Fecal zonulin-related proteins (ZRP) provide a non-invasive marker of intestinal barrier integrity.

Calprotectin, a pro-inflammatory protein complex released from neutrophils, serves as a reliable biomarker of mucosal inflammation. While typically normal in functional disorders such as irritable bowel syndrome (IBS), fecal calprotectin (FC) is significantly elevated in inflammatory bowel diseases (IBD), helping to distinguish organic inflammatory conditions from functional disorders.

Lactose intolerance (LI) results from lactase deficiency and is characterized by abdominal pain, bloating, and diarrhea. Traditionally attributed to mechanical and fermentative processes, recent evidence suggests that immunological and inflammatory mechanisms may also contribute. LI can be primary (genetic lactase deficiency) or secondary (due to epithelial damage or barrier dysfunction), with barrier disruption potentially exacerbating symptom severity.

Recent studies have reported elevated fecal calprotectin in individuals with self-reported milk intolerance (Seidita et al., 2023), even among those confirmed as lactose intolerant by hydrogen breath testing, suggesting that additional inflammatory or allergic mechanisms may be involved. Moreover, dietary interventions in IBS patients with food intolerances, including lactose, have been shown to significantly reduce calprotectin levels (Schnedl et al., 2023), indicating that inflammation may be modifiable.

Therefore, evaluating zonulin and calprotectin levels in lactose-intolerant adults can provide insights not only into mechanical or chemical causes of symptoms but also into intestinal barrier dysfunction and underlying inflammation. Current literature on combined assessment of these biomarkers in adults is limited. This study aims to:

Investigate the relationship between lactose intolerance and zonulin/fecal calprotectin levels.

Assess the independent contribution of zonulin (intestinal permeability) separate from calprotectin (inflammation).

Explore associations between these biomarkers, symptom severity, and quality of life.

Первичные конечные точки

• To determine the relationship between lactose intolerance (LI) and fecal biomarkers, zonulin (Z) and fecal calprotectin (FC), in adults with IBS. [Срок оценки: Baseline assessment (single time point measurement of biomarkers and symptoms)]

Вторичные конечные точки (1)

• FC predictive value with Z. Z correlation with symptom severity. Z in IBS subtypes / FC and organic pathology. Z mediation between LI and symptoms. IgE anti-casein and symptom severity. LTT correlation with IP biomarkers. Celiac serology prevalence. [Срок оценки: Baseline assessment (single measurement at the time of evaluation)]

Критерии участия

Критерии включения

• Adults aged 18-70 years; experiencing chronic symptoms (diarrhea, bloating, abdominal pain, constipation, flatulence) for the past 3 months, potentially fitting IBS criteria.

Критерии исключения

\- Acute gastroenteritis (< 4 weeks), Active gastrointestinal bleeding (stomach, small intestine, and colon), Known celiac disease, Bariatric surgery or short bowel syndrome, Pregnancy or lactation, Type I and II Diabetes mellitus, Antibiotic use within the last 2 weeks, High-dose NSAIDs within the last 2 weeks, Initiation of probiotics or prebiotics within the last 4 weeks, High-dose PPI use (optional), Inflammatory bowel disease (IBD; ulceretive colitis and Crohn's colitis) with active severe flare (excluded from primary analyses, evaluated separately in subgroup analyses)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Другое

Центры проведения

Turkey (Türkiye) · 1 центр

• Bezmialem Vakıf University Medical Faculty Hospital — Istanbul

Публикации

• Guingand DE Rivery M, Zeinab H, Cohen V, Baumstarck K, Luciano L, Vitton V. Does fecal calprotectin increase may be linked to lactose intolerance in patients with irritable bowel syndrome? Minerva Gastroenterol (Torino). 2023 Sep;69(3):329-334. doi: 10.23736/S2724-5985.21.02802-6. Epub 2021 Apr 8. PMID 33829725
• Jendraszak M, Galecka M, Kotwicka M, Schwiertz A, Regdos A, Pazgrat-Patan M, Andrusiewicz M. Impact of Biometric Patient Data, Probiotic Supplementation, and Selected Gut Microorganisms on Calprotectin, Zonulin, and sIgA Concentrations in the Stool of Adults Aged 18-74 Years. Biomolecules. 2022 Nov 29;12(12):1781. doi: 10.3390/biom12121781. PMID 36551209
• Tyszka M, Maciejewska-Markiewicz D, Bilinski J, Lubas A, Stachowska E, Basak GW. Increased Intestinal Permeability and Stool Zonulin, Calprotectin and Beta-Defensin-2 Concentrations in Allogenic Hematopoietic Cell Transplantation Recipients. Int J Mol Sci. 2022 Dec 15;23(24):15962. doi: 10.3390/ijms232415962. PMID 36555600
• Czaja-Bulsa G, Bulsa K, Lokiec M, Drozd A. Can Faecal Zonulin and Calprotectin Levels Be Used in the Diagnosis and Follow-Up in Infants with Milk Protein-Induced Allergic Proctocolitis? Nutrients. 2024 Sep 2;16(17):2949. doi: 10.3390/nu16172949. PMID 39275265
• Szymanska E, Wierzbicka A, Dadalski M, Kierkus J. Fecal Zonulin as a Noninvasive Biomarker of Intestinal Permeability in Pediatric Patients with Inflammatory Bowel Diseases-Correlation with Disease Activity and Fecal Calprotectin. J Clin Med. 2021 Aug 30;10(17):3905. doi: 10.3390/jcm10173905. PMID 34501351
• Schnedl WJ, Michaelis S, Enko D, Mangge H. Fecal Calprotectin Elevations Associated with Food Intolerance/Malabsorption Are Significantly Reduced with Targeted Diets. Nutrients. 2023 Feb 27;15(5):1179. doi: 10.3390/nu15051179. PMID 36904178
• Seidita A, Mansueto P, Giuliano A, Chiavetta M, Soresi M, Carroccio A, The Internal Medicine Study Group. Fecal Calprotectin in Self-Reported Milk Intolerance: Not Only Lactose Intolerance. Nutrients. 2023 Feb 20;15(4):1048. doi: 10.3390/nu15041048. PMID 36839406
• Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011 Jan;91(1):151-75. doi: 10.1152/physrev.00003.2008. PMID 21248165

Идентификаторы

NCT: NCT07424898 · E-54022451-050.04-212534

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗