Celiac disease (CD) is a well-established immune-mediated enteropathy triggered by dietary gluten in genetically susceptible individuals. Although the central role of HLA-DQ2/DQ8–restricted immune responses is clearly defined, environmental modifiers increasingly appear to influence disease expression, symptom severity, and clinical heterogeneity.1 Among these modifiers, intestinal microorganisms have received growing attention; however, intestinal protozoa remain relatively understudied in this context. The article “Intestinal protozoa in celiac disease: detection and phylogenetic characterisation” published in this issue of Tropical Parasitology addresses this gap by systematically evaluating intestinal protozoan parasites in patients with CD using microscopy, serology, quantitative polymerase chain reaction (qPCR), and phylogenetic analysis. The study provides an important contribution at the interface of parasitology, gastroenterology, and mucosal immunology. A key strength of the study is its emphasis on molecular diagnostics. Conventional microscopy frequently underestimates protozoan prevalence because of low parasite burden, intermittent shedding, and morphological overlap among intestinal protozoa. The substantially higher detection rates of Dientamoeba fragilis and Blastocystis hominis by qPCR compared with microscopy reinforce the growing consensus that molecular methods are essential for accurate detection, particularly in patients with chronic gastrointestinal disease.2 This observation is especially relevant in endemic and semiendemic regions where parasitic infections are common but often underdiagnosed. The finding of significantly higher positivity rates for D. fragilis and B. hominis in CD patients compared with healthy controls raises important biological and clinical questions. Whether these protozoa actively contribute to mucosal immune activation or preferentially colonize the altered intestinal environment characteristic of CD remains unclear. Importantly, the authors appropriately frame their conclusions as associations rather than causal relationships, consistent with the cross-sectional design of the study. Similar observations of Blastocystis colonization in symptomatic CD patients have been reported previously,3 lending further relevance to the present findings. A particularly noteworthy aspect of the work is the phylogenetic characterization of D. fragilis. The identification of three genotypes, clustering with both genotype 1 and genotype 2 reference strains, adds a valuable molecular dimension. Previous studies indicate that genotype 1 predominates globally, whereas genotype 2 is less frequently reported and remains poorly characterized.4 The detection of both genotypes within a CD cohort suggests that host-related factors — such as altered mucosal immunity or epithelial integrity – may influence genotype distribution or persistence. Although the clinical implications of these genotypes remain speculative, their identification provides a foundation for future genotype–phenotype correlation studies. From a broader immunological perspective, these findings align with emerging evidence that intestinal protozoa can modulate host immune responses and interact with the gut microbiota.5 In CD, where epithelial barrier dysfunction and immune dysregulation are central features, protozoa may act as modifiers of disease expression rather than primary etiological agents. This concept is supported by experimental and clinical studies demonstrating immune modulation by parasitic infections in immune-mediated intestinal conditions.6,7 The clinical implications of this work are also relevant. Persistent gastrointestinal symptoms in patients with CD, even after adherence to a gluten-free diet, remain a common challenge. The findings suggest that targeted molecular screening for intestinal protozoa may be useful in selected patients, particularly in endemic settings. Identification and treatment of concomitant protozoan infections may help alleviate symptom burden and improve quality of life, irrespective of their direct role in disease pathogenesis.8 The authors appropriately acknowledge important limitations, including the relatively small and unmatched control group and the inability to infer causality. These limitations underscore the need for further research, including longitudinal studies, treatment-naïve cohorts, microbiome profiling, and functional immunological investigations. In summary, this study provides robust molecular and phylogenetic data on intestinal protozoa in CD and highlights an underexplored aspect of gut–immune interactions. By integrating modern molecular diagnostics with classical parasitology, the authors offer insights of relevance to parasitologists, clinicians, and researchers working in gastrointestinal and immune-mediated diseases. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
A. Mohan Kumar (Thu,) studied this question.