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Review

The Role of Blastocystis spp. in the Etiology of Gastrointestinal and Autoimmune Diseases

by
Oliwia Pawelec-Pęciak
1,
Natalia Łanocha-Arendarczyk
1,*,
Konrad Grzeszczak
2 and
Danuta Kosik-Bogacka
1
1
Department of Biology, Parasitology and Pharmaceutical Botany, Pomeranian Medical University in Szczecin, Powstanców Wielkopolskich 72, 70-111 Szczecin, Poland
2
Department of Medical Analytics, Pomeranian Medical University in Szczecin, Powstanców Wielkopolskich 72, 70-111 Szczecin, Poland
*
Author to whom correspondence should be addressed.
Pathogens 2025, 14(4), 313; https://doi.org/10.3390/pathogens14040313
Submission received: 21 February 2025 / Revised: 20 March 2025 / Accepted: 23 March 2025 / Published: 25 March 2025
(This article belongs to the Section Parasitic Pathogens)
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Versions Notes

Abstract

:
Blastocystis spp. has been linked to gastrointestinal symptoms, yet its pathogenicity remains uncertain. In addition, the roles of virulence factors, pathogenic potential, and host-specific traits associated with symptomatic infections are still not well understood. The growing number of immunocompromised patients has contributed to an increasing prevalence of Blastocystis spp. infections, which may be implicated in the development of various inflammatory diseases, including irritable bowel syndrome (IBS), colorectal cancer, and autoimmune disorders such as Hashimoto’s disease and ulcerative colitis. However, the presence of nonspecific symptoms often complicates diagnosis. This study aimed to present current data on the impact of Blastocystis spp. on the development and progression of gastrointestinal and autoimmune diseases, as well as to explore potential treatment options for Blastocystis spp. infections. A literature review was conducted to analyze the role of Blastocystis spp. in the pathogenesis of specific diseases and to investigate potential mechanisms of its interaction with the host organism. Advances in diagnostic techniques, particularly PCR, allow not only for the detection of Blastocystis spp. but also for the identification of specific subtypes, improving treatment precision. Beyond conventional therapies like metronidazole, there is a growing emphasis on alternative treatments, including the use of medicinal plants and probiotics.

1. Introduction

Protozoa of the genus Blastocystis are unicellular, anaerobic, eukaryotic organisms that colonize the gastrointestinal tract of various mammals, including humans. Although they were initially considered commensals of the large intestine due to their asymptomatic presence, subsequent clinical observations and patient-reported symptoms have suggested their potential pathogenicity. Today, Blastocystis spp. is recognized as a possible etiological agent of chronic diarrhea, particularly in immunocompromised individuals, as well as in patients with functional bowel disorders, malnutrition, cancer, or those who have undergone organ transplantation [1,2,3,4].
The current taxonomic classification of Blastocystis is as follows: Kingdom Sar, Phylum Stramenopiles, Class Bigyra, Order Opalinata, Family Blastocystidae, and Genus Blastocystis [5,6]. The species-level classification remains unresolved. Historically, species names were assigned based on the host from which the protozoan was isolated (e.g., Blastocystis hominis, B. ratti). Studies have shown that host specificity and pathogenic potential correlate with variations in the sequence of the small subunit ribosomal RNA (SSU rRNA) [1,7,8]. Molecular analysis of the SSU rRNA gene has identified at least 42 subtypes (STs) of Blastocystis spp. across various animals and humans [9], with some subtypes suspected to be pathogenic [10]. In humans, 16 subtypes have been identified to date, with ST1–ST4 being the most commonly associated with infection [9,11]. Given the unresolved species classification, the appropriate nomenclature is Blastocystis spp., with subtypes determined based on molecular SSU rRNA or SSU rDNA analysis [1].
Blastocystis spp. exhibit diverse morphological forms that vary in structure and size and can transition between forms in response to environmental factors. These include vacuolar, avacuolar, multivacuolar, granular, amoeboid, and cystic forms [12]. Transmission occurs via the fecal–oral route, with the cyst serving as the infectious stage. After ingestion, the cyst undergoes excystation in the host’s gastrointestinal tract, releasing vacuolar forms capable of binary fission. These forms subsequently encyst in the intestinal lumen, producing new cysts that are excreted in feces, completing the transmission cycle [1].
Human infection with Blastocystis spp. primarily results from ingestion of cysts present in contaminated water and food (e.g., improperly washed vegetables and fruits). Direct transmission through contact with animal reservoirs, including livestock (pigs, goats, sheep, cattle) and birds, is also possible [13,14]. The prevalence of infection is influenced by several risk factors, such as sanitation infrastructure, hygiene practices, age, overall health, nutritional status, and lifestyle habits, including hand hygiene and water consumption practices [15].
An estimated one billion people worldwide are infected with Blastocystis spp., with prevalence rates ranging from 1.5–10% in developed countries to 30–50% in developing regions [16]. In immunocompetent individuals, infections are often asymptomatic or manifest as mild, nonspecific symptoms such as bloating and intestinal cramps [17]. However, immunocompromised individuals—including those with HIV/AIDS, cancer, organ transplants, and those undergoing immunosuppressive therapy or hemodialysis—are particularly vulnerable. The estimated prevalence in this population averages 10% across high- and middle-income countries [18,19,20]. In these patients, Blastocystis spp. infection can lead to severe diarrhea due to progressive immune dysfunction [21]. Animal models suggest that impaired immunity exacerbates disease severity, as evidenced by extensive intestinal involvement and increased production of proinflammatory cytokines and antibodies compared to immunocompetent individuals [22].
Symptomatic blastocystosis may present as chronic diarrhea, abdominal pain, nausea, vomiting, anorexia, weight loss, and general weakness. Additionally, non-gastrointestinal symptoms such as rash, pruritus, and joint pain have been reported [3,23]. In patients with comorbidities or immunosuppression, Blastocystis spp. infections can be life-threatening [24].
Diagnosis primarily relies on direct microscopic examination of stool smears [23,25]. The vacuolar form is most frequently detected, whereas other morphological forms are more challenging to identify and may be confused with microorganisms, leukocytes, lipid droplets, or other fecal components [2]. Serological methods have limited utility, as their diagnostic value is still under investigation. Although culture methods offer high sensitivity, they are time-consuming and require specific growth conditions that are difficult to maintain [2,23]. Given these limitations, molecular diagnostic techniques, particularly polymerase chain reaction (PCR), are increasingly favored. PCR not only offers high sensitivity but also enables subtype differentiation [23,26]. Studies indicate that PCR is superior to traditional diagnostic methods for confirming Blastocystis spp. infections [27]. Furthermore, PCR techniques exhibit higher sensitivity, specificity, and predictive values compared to culture and microscopy [28,29].
The role of Blastocystis spp. in human gastrointestinal health remains a subject of ongoing scientific investigation [2]. Research is exploring its potential involvement in the pathogenesis of colorectal cancer, irritable bowel syndrome (IBS), and autoimmune diseases such as ulcerative colitis and Hashimoto’s thyroiditis [30,31,32,33].

2. Materials and Methods

This review was based on scientific publications retrieved from online databases, including PubMed, MDPI, NCBI, and Google Scholar, with the final search conducted in January 2025. Articles were identified using the following keywords: “Blastocystis”, “gastrointestinal diseases”, “irritable bowel syndrome”, “colorectal cancer”, “autoimmune diseases”, “treatment”, “metronidazole”, “medicinal plants”, and “probiotics”. This review encompasses comprehensive reviews, original research case reports, and articles written in English and published in peer-reviewed journals. We excluded brief communications and gray literature (e.g., conference proceedings and abstracts). Upon application of these criteria, a total of 154 papers were shortlisted for review. A narrative review was then conducted, selecting the most relevant and informative studies for inclusion.
This study aimed to present current data on the impact of Blastocystis spp. on the development and progression of gastrointestinal and autoimmune diseases, as well as to explore potential treatment options for Blastocystis spp. infections. A literature review was conducted to analyze the role of Blastocystis spp. in the pathogenesis of specific diseases and to investigate potential mechanisms of its interaction with the host organism.

3. Blastocystis spp. and Gastrointestinal Diseases

3.1. Irritable Bowel Syndrome (IBS)

Irritable bowel syndrome is a chronic functional gastrointestinal disorder affecting 10–20% of the population, with the highest prevalence reported in Western Europe and North America [29,34]. IBS is characterized by altered bowel movement patterns, changes in stool consistency, bloating, excessive gas production, and abdominal pain associated with either diarrhea or constipation [29,35,36]. The exact etiology of IBS remains unclear, but it is believed to involve a combination of psychosocial factors, altered gut motility and hypersensitivity, and disturbances in the gut microbiota [29]. Studies suggest that IBS can develop following gastrointestinal infections (post-infectious IBS) or as a consequence of prolonged broad-spectrum antibiotic use [36,37,38]. Environmental and dietary factors have also been implicated in IBS pathogenesis [35].
Recent research has established a link between parasitic infections and IBS symptoms. A study by Das et al. [39] found that 56% of IBS patients were co-infected with gastrointestinal parasites, including Giardia intestinalis and Entamoeba histolytica. The high prevalence of Blastocystis spp. in IBS patients further suggests a potential role in the disorder’s pathogenesis [39,40,41,42]. For instance, Ibrahim et al. [43] reported a significantly higher prevalence of Blastocystis spp. in IBS patients (33.5%) compared to the control group (12%). Nahhas [44] observed an even higher infection rate, with Blastocystis spp. detected in 71.4% of IBS patients. Additionally, a reduction in IBS symptoms following antiparasitic treatment further supports the possible involvement of Blastocystis spp. in IBS pathogenesis. Kesuma et al. [31] demonstrated an association between Blastocystis ST1 and diarrhea-predominant IBS in Indonesian adolescents, where Blastocystis spp. was identified in 36.5% of IBS patients, and diarrhea occurred three times more frequently in individuals infected with Blastocystis ST1.
Despite these findings, it remains unclear whether IBS-related gut dysfunction facilitates Blastocystis spp. colonization or whether the presence of the protozoan contributes to intestinal disturbances, ultimately leading to IBS symptoms [36].
Intestinal parasites may influence gastrointestinal function by increasing gut permeability, triggering immune responses, and promoting chronic inflammation [45,46]. Epithelial barrier dysfunction has been observed in duodenal tissue from patients with chronic giardiasis [47], while studies in animal models have demonstrated altered intestinal motility and visceral sensitivity in Trichinella spiralis infection [48]. Several mechanisms have been proposed to explain Blastocystis spp. interactions with the immune system and their effects on gut function. One such mechanism involves the ability of Blastocystis spp. to produce cysteine proteases that degrade glycoproteins within mucin, a key component of the gastrointestinal mucus layer [35]. Mucin plays an essential role in maintaining gut hydration, protecting epithelial cells from stress, and preventing pathogen infection [49]. Degradation of mucin may initiate inflammatory and allergic responses [35]. Moreover, Blastocystis spp. has been shown to disrupt the integrity of the intestinal barrier by modulating tight junction proteins (TJs), such as claudin-7, leading to increased epithelial permeability. This disruption may heighten intestinal sensitivity to external stimuli, potentially contributing to IBS symptoms [36].
A correlation has also been identified between Blastocystis spp. infection and elevated proinflammatory cytokine levels. Ragavan et al. [29] reported significantly higher levels of interleukins (IL-3, IL-5, and IL-8) in IBS patients infected with Blastocystis spp. compared to uninfected individuals. Similarly, Ismail et al. [50] found increased plasma concentrations of IL-6, IL-8, IL-10, IFN-γ, and TNF-α in IBS patients with Blastocystis spp. infection. Furthermore, single nucleotide polymorphisms (SNPs) in IL-8 and IL-10 have been suggested as potential risk factors for IBS development in infected individuals [51]. Hussain et al. [52] provided further support for this hypothesis, observing elevated antibody levels against Blastocystis spp. in IBS patients compared to control subjects.
Dysbiosis has also been proposed as a contributing factor to IBS [53] and Blastocystis spp. may influence both the composition and diversity of gut microbiota. Studies have shown that Blastocystis spp. can reduce the abundance of beneficial bacteria such as Lactobacillus spp. and Bifidobacterium spp. [54]. Additionally, its presence has been associated with a decreased Firmicutes/Bacteroidetes ratio in individuals with metabolic disorders compared to healthy controls [55]. Some studies have also suggested a synergistic relationship between Blastocystis spp. and Clostridium difficile, with both organisms being co-detected in patients with diarrhea [56,57].
Although many studies support an association between IBS and Blastocystis spp., others have failed to establish a significant correlation [58,59]. Further large-scale studies are needed to elucidate the precise role of Blastocystis spp. in IBS pathogenesis.

3.2. Blastocystis spp. and Colorectal Cancer (CRC)

Colorectal cancer (CRC) is the third most frequently diagnosed malignancy and the second leading cause of cancer-related mortality worldwide [60]. Its development is influenced by a range of risk factors, including chronic infections and inflammation, poor dietary habits, stress, and prolonged exposure to radiation and toxic chemicals [61]. Infectious agents, including parasites, are estimated to contribute to approximately 16% of all cancers [62]. Several bacterial species, such as Fusobacterium nucleatum, Bacteroides fragilis, Escherichia coli, and Helicobacter pylori, have been implicated in the initiation and progression of CRC [63]. Similarly, the increased prevalence of Blastocystis spp. in CRC patients suggests a potential role of this protozoan in carcinogenesis [64].
A review of the literature indicates that Blastocystis spp. is detected more frequently in CRC patients than in healthy individuals, with reported prevalence rates ranging from 2.8% to 52%, predominantly involving subtypes ST1 and ST3 [30,65,66]. Notably, Ali et al. [65] were the first to report the presence of the less common subtype ST7 in three patients with colonic adenocarcinoma (grade 2) and a history of colectomy. This subtype has been associated with gut microbiota dysbiosis and a reduction in beneficial bacterial populations, such as Lactobacillus spp. and Bifidobacterium spp. [54,67]. In CRC patients, Blastocystis spp. has been identified in colonic washouts (12.47%) and fecal samples (6.12%) [68]. Interestingly, chemotherapy does not appear to influence the presence of Blastocystis spp. [64]. Additionally, Blastocystis spp. has been documented in advanced CRC stages (grades 3 and 4), where its presence correlates with elevated levels of proinflammatory cells and increased plasma TNF-α [69]. These findings suggest that tumor-induced changes in the colonic environment may facilitate Blastocystis spp. colonization.
Conversely, several researchers propose that Blastocystis spp. is not merely an opportunistic colonizer but may act as a contributing factor to CRC development. Kumarasamy et al. [70] conducted an animal model study comparing the effects of azoxymethane (AOM), a known carcinogen, with the combined exposure to AOM and Blastocystis spp. cysts (ST3). Their findings revealed that simultaneous exposure to ST3 and AOM led to a twofold increase in the number of aberrant crypt foci in the colon compared to rats exposed to AOM alone. It has also been suggested that Blastocystis spp. may induce oxidative stress, disrupt epithelial homeostasis, and promote intestinal barrier dysfunction, all of which contribute to CRC pathogenesis [64].
In vitro studies have further demonstrated that Blastocystis spp. enhances the proliferation of HCT116 colorectal cancer cells. This effect may be mediated through the activation of immune regulatory proteins, such as cathepsin B, which has been identified as a key factor in CRC progression, invasion, and metastasis [71,72]. Moreover, Blastocystis spp. infections have been linked to the suppression of nitric oxide synthase (NOS), leading to a reduction in nitric oxide levels, which are essential for immune defense and tumor suppression [73].
Another mechanism by which Blastocystis spp. may contribute to CRC is its ability to trigger the release of proinflammatory cytokines, including IL-8, IL-6, IL-1β, and TNF-α, which activate multiple signaling pathways involved in tumorigenesis (Figure 1). This process may lead to increased stem cell activity, enhanced cellular proliferation and migration, and the promotion of angiogenesis, all of which support cancer progression [64].
Additionally, Blastocystis spp. has been shown to compromise intestinal barrier integrity by disrupting tight junction (TJ) proteins, such as claudins and occludins, which maintain epithelial cohesion [74]. Increased epithelial permeability can contribute to leaky gut syndrome, a recognized risk factor for CRC [75]. Furthermore, Blastocystis spp. has been implicated in the downregulation of zonula occludens-1 (ZO-1), a tumor suppressor protein. Reduced ZO-1 expression results in a weakened epithelial barrier and increased colorectal cancer cell proliferation [64]. Similarly, Blastocystis hominis and Blastocystis ratti WR1 have been shown to stimulate the release of inflammatory cytokines, particularly IL-8, via NF-κB activation [76]. Evidence also suggests that Blastocystis spp. may promote colorectal cancer cell proliferation by dysregulating IFN-γ and p53 expression, further highlighting its potential role in carcinogenesis [77].
Despite the strong association between Blastocystis spp. infections and CRC observed in various studies, many questions remain unanswered. The specific role of the protozoan in different stages of CRC progression has yet to be fully elucidated, and it is unclear whether Blastocystis spp. alone can initiate malignant transformation [30]. Current data remain insufficient to draw definitive conclusions regarding the significance of Blastocystis spp. in CRC, emphasizing the need for further research.

4. Blastocystis spp. in Autoimmune Diseases

Autoimmune diseases result from a complex interplay of genetic and environmental factors, leading to excessive immune activation and the production of autoantibodies against self-tissues [78,79]. Similarly, many pathogenic and virulent factors can trigger autoimmune reactions through various mechanisms [80]. Changes in the gut microbiota composition, including those induced by Blastocystis spp., have been identified as potential contributors to immune dysregulation and the onset of autoimmune diseases [67,81].
The involvement of Blastocystis spp. in autoimmune thyroiditis, particularly Hashimoto’s disease, has been highlighted in several studies [33,82]. Interleukin-17 (IL-17) is considered a key factor in the disease’s pathogenesis, alongside elevated levels of anti-thyroid peroxidase (anti-TPO) antibodies and increased thyroid-stimulating hormone (TSH), which indicate thyroid dysfunction [33,83,84]. El-Zawawy et al. [33] observed significantly higher IL-17 levels in the plasma of Hashimoto’s patients infected with Blastocystis spp. compared to uninfected individuals. Notably, Blastocystis spp. eradication led to a decrease in IL-17 levels and an improvement in thyroid function parameters. Similar findings were reported by Rajič et al. [82], who described a 49-year-old male with Hashimoto’s disease, where Blastocystis spp. eradication resulted in normalized thyroid hormone levels, reduced anti-thyroid antibody concentrations, and the resolution of disease symptoms.
There is also evidence linking Blastocystis spp. to cutaneous lesions and urticaria [85]. Chronic spontaneous urticaria (CSU) is a condition characterized by recurrent wheals and/or angioedema persisting for at least six weeks. The underlying causes are believed to include autoimmune reactions, food intolerances, bacterial and viral infections, and parasitic infestations [86]. Jafari et al. [87] found a significantly higher prevalence of Blastocystis spp. in urticaria patients compared to controls. While both groups harbored ST1, ST2, and ST3, no correlation was identified between specific subtypes and symptom severity. However, Aykur et al. [88] observed a strong association between ST3 and CSU development. Additionally, amoeboid forms of Blastocystis spp., which are considered the most virulent, were predominantly isolated from patients with chronic urticaria [89,90]. Amoeboid Blastocystis forms are thought to adhere more effectively to intestinal epithelial cells, disrupt gut homeostasis, and trigger immune responses against parasite surface antigens, leading to inflammatory cell recruitment [90]. This immune activation promotes histamine release, which may contribute to allergic reactions and chronic urticaria [91].
The presence of Blastocystis spp. has also been documented in patients with ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD) of unknown etiology, characterized by mucosal and submucosal inflammation of the colon [92]. However, multiple studies have found no clear association between Blastocystis spp. and UC development [32,93]. Kök et al. [32] reported no significant difference in Blastocystis spp. prevalence between remission and active disease phases. Interestingly, UC patients infected with Blastocystis spp. exhibited milder symptoms, suggesting a potential protective effect [32]. In contrast, Rossen et al. [94] observed a lower prevalence of Blastocystis spp. in UC patients compared to healthy individuals, possibly due to increased protozoan clearance in response to chronic intestinal inflammation [94].
The role of Blastocystis spp. in autoimmune diseases remains uncertain. While its immune-modulating effects may contribute to Hashimoto’s disease and chronic urticaria, evidence suggests a potential protective role in ulcerative colitis. Due to the limited data available, further research is necessary to clarify the significance of Blastocystis spp. in autoimmune disease pathogenesis.
The prevalence of Blastocystis spp. in various gastrointestinal and autoimmune diseases, along with the most frequently detected subtypes, is summarized in Table 1. Differences in reported prevalence may stem from disease-specific factors, sample size variations, and discrepancies in diagnostic methodologies. The most commonly employed diagnostic methods for Blastocystis spp. infections in patients with gastrointestinal and autoimmune diseases include microscopic examination using various staining techniques and molecular methods, particularly polymerase chain reaction (PCR). Keshawy and Alabbassy [95] demonstrated that PCR-based detection was more accurate than direct microscopy, identifying Blastocystis spp. in 10 out of 24 samples, whereas microscopy detected only 2 positive cases. Additionally, PCR enables subtype differentiation, which has revealed that ST1, ST2, and ST3 are the most prevalent subtypes in gastrointestinal and autoimmune diseases, though minor variations in subtype distribution exist across studies [87,96,97].
Blastocystis spp. infections often present with nonspecific gastrointestinal symptoms, including diarrhea, irregular bowel movements, bloating, and abdominal pain. However, in patients with chronic urticaria, gastrointestinal symptoms are rarely observed.
Table 1. Prevalence of Blastocystis spp. in gastrointestinal and autoimmune diseases (SLE, systemic lupus erythematosus; IBS, irritable bowel syndrome; UC, ulcerative colitis; CD, celiac disease; CRC, colorectal cancer; DM, direct microscopy; PCR, polymerase chain reaction).
Table 1. Prevalence of Blastocystis spp. in gastrointestinal and autoimmune diseases (SLE, systemic lupus erythematosus; IBS, irritable bowel syndrome; UC, ulcerative colitis; CD, celiac disease; CRC, colorectal cancer; DM, direct microscopy; PCR, polymerase chain reaction).
ConditionSymptomsSamples (n)Positive
Blastocystis Samples (n)		Prevalence (%)Diagnostic Method (Stool Examination)Most Common SubtypeReferences
SLEInflammation, vasculitis, immune complex deposition, vasculopathy38513.2DM (trichrome staining), PCRNo data[98]
SLE and IBSNo data241041.6PCRST3[95]
28.3DM (saline/iodine)
UCNo data21523.8DM (trichrome staining), PCRNo data[98]
UCAcute diarrhea, loss of appetite, dyspepsia, constipation, abdominal pain276248.7Native-Lugol, formol = ethyl acetate concentrationNo data[99]
UCNo data150128DM, Jones’ medium culture, PCRST3[100]
IBSAbdominal pain or discomfort, improvement with defecation, change in frequency of defecation, change in stool form1222419.7DM (trichrome staining), PCRST3[59]
IBSRecurrent abdominal pain, improvement with defecation, change in frequency of defecation, change in stool form1152219.1DM (wet mount, trichrome staining), Jones’ medium culture, PCRST3[101]
IBSDiarrhea, constipation, abdominal pain, flatulence, weight loss, nausea, vomiting352571.4DM, PCRST1[44]
CDNo data921516.3PCRST1, ST2, ST3[97]
CDNo data753141.3DM, PCRST3[102]
CRCNo data15960DM (Wheatley Trichrome), PCRST2[103]
CRCNo data742229.7Jones’ medium culture, DM, PCRST1[66]
UrticariaSkin lesions with or without gastrointestinal symptoms543361.1DM, PCRST3[89]
UrticariaSkin lesions1354331.9Direct saline smear, Lugol’s iodine staining, trichrome staining, Jones’ medium culture, PCRST3[88]
UrticariaSkin lesions942021.3DM, PCRST1, ST2, ST3[87]
SpondyloarthritisDiarrhea, mucus in stool, hematochezia, increased frequency of daily bowel movements, abdominal pain, abdominal distension745067.6PCRST1, ST2, ST3[96]

5. Treatment of Blastocystis spp. Infections

5.1. Conventional Treatment

In many cases, Blastocystis spp. infections do not require treatment due to their self-limiting nature. However, therapy is recommended for patients experiencing persistent and severe symptoms that significantly impair daily functioning [18,104,105]. Various antimicrobial agents have been used to treat Blastocystis spp. infections, with varying degrees of effectiveness. Currently, metronidazole, a nitroimidazole derivative, is considered the drug of choice. Its mechanism of action involves disrupting microbial DNA and inducing cell death [104,105].
Metronidazole is typically administered at doses ranging from 250 to 750 mg three times daily or 1500 mg once daily for ten days. Combination therapies, such as metronidazole with trimethoprim–sulfamethoxazole or paromomycin, have also been increasingly used [18]. Several studies have highlighted the high efficacy of metronidazole and its superiority over other antimicrobial agents [106,107,108,109,110]. Following metronidazole therapy, approximately 90% of patients achieve disease remission with no recurrence within six months [105]. However, literature reviews indicate that the eradication rate of Blastocystis spp. varies widely, ranging from 0% to 100% [104,105,111].
The variability in treatment response may be due to regional differences in drug susceptibility, as well as emerging resistance to chemotherapeutic agents [18,104,105,111,112]. Certain Blastocystis spp. subtypes may exhibit natural resistance to metronidazole, or their susceptibility may depend on drug concentration [104,113,114]. The cystic form of Blastocystis spp. may also be resistant to metronidazole’s cytotoxic effects, as its thick-walled structure allows survival under extreme environmental conditions [104,105]. Studies have shown that cysts can withstand metronidazole concentrations of up to 5 mg/mL [113]. Another possible explanation for metronidazole resistance in Blastocystis spp. is reduced activity of the pyruvate:ferredoxin oxidoreductase enzyme, which is required for activating the drug (Figure 2) [115]. This mechanism has also been observed in other protozoan parasites, including metronidazole-resistant Giardia intestinalis [116].
The occurrence of adverse effects is another limitation of metronidazole therapy. The drug may cause gastrointestinal disturbances, and in rare cases, long-term or high-dose use can lead to serious health complications. Severe side effects include neurotoxicity, hepatic encephalopathy, peripheral neuropathy, and optic neuropathy [117]. There is also evidence suggesting that metronidazole possesses carcinogenic, teratogenic, embryotoxic, and genotoxic potential [117,118].
Recent research suggests that metronidazole resistance may increase the pathogenicity of Blastocystis spp. Rajamanikam et al. [119] examined parasite growth, apoptosis, protease activity, and the ability of Blastocystis spp. to promote cancer cell proliferation after exposure to metronidazole at a concentration of 0.001 mg/mL. Their findings showed an increase in the number of parasites, particularly amoeboid forms, as well as a significant rise in cysteine protease activity, an enzyme playing a crucial role in the Blastocystis spp. cell cycle. Additionally, an enhanced ability to promote cancer cell proliferation was observed, indicating a higher pathogenic potential in resistant strains. In contrast, Wu et al. [74] found that metronidazole-resistant ST7 strains exhibited reduced pathogenicity, likely due to impaired adhesion to intestinal epithelial cells.
The successful elimination of Blastocystis spp. depends on maintaining a sufficient drug concentration in the intestine to effectively destroy the protozoan [104]. In addition to metronidazole, trimethoprim–sulfamethoxazole and nitazoxanide have demonstrated similar efficacy and are currently considered second-line treatments for blastocystosis. Both drugs are well tolerated and do not typically cause severe adverse effects [105]. Paromomycin, a broad-spectrum aminoglycoside antibiotic, has also been used to treat skin lesions associated with Blastocystis spp. infections [120]. Several other drugs, including tinidazole, ketoconazole, pentamidine, quinine, iodoquinol, furazolidone, and emetine, have shown varying degrees of effectiveness and may be considered alternative options when metronidazole and second-line therapies fail [121].
Despite the availability of multiple chemotherapeutic agents active against Blastocystis spp., complete eradication remains challenging. The primary obstacles to treatment success include variability in drug susceptibility among different Blastocystis subtypes, geographic differences in resistance patterns, and the emergence of drug-resistant strains. Additionally, factors such as poor adherence to treatment regimens, differences in drug pharmacokinetics, and inactivation of therapeutic compounds by the host’s natural microbiota further contribute to treatment failure [105]. Given these limitations, researchers have increasingly turned their attention to alternative therapeutic strategies, particularly natural compounds with potential antiparasitic properties.

5.2. Alternative Treatments

Recent studies have explored the potential of natural compounds and medicinal plants as alternative therapies for Blastocystis spp. infections. Certain plant extracts and dietary components have demonstrated antiparasitic activity, which may aid in the eradication of the protozoan (Table 2).
One of the most promising medicinal plants is Salvadora persica L., widely used as a natural oral hygiene agent. Studies have shown that aqueous extracts from its roots exhibit strong activity against Blastocystis subtypes ST1, ST3, and ST5. Inhibition of Blastocystis spp. growth reached 80% after 48 h of incubation in an extract concentration of 40 µL/mL. Notably, S. persica extracts retained their protozoicidal properties even at high temperatures [122].
Traditional Chinese medicine has also provided insights into potential anti-Blastocystis treatments. Extracts from linalool (Boesenbergia rotunda (L.) Mansf.) and Ganoderma lucidum (Fr.) Kart have demonstrated amoebicidal activity. When combined with metronidazole at a concentration of 62.5 µg/mL, these extracts inhibited protozoan growth by up to 90% within 12 h [123]. Their active components, including geraniol, camphor, linalool, and versalide (Ganoderma lucidum), are thought to be responsible for the observed antiparasitic effects.
Another promising plant is Eurycoma longifolia, known as Tongkat Ali. Alcoholic extracts of this plant have exhibited activity against Blastocystis spp. comparable to metronidazole [124]. The primary bioactive compound, eurycomanone, is believed to be mainly responsible for its protozoicidal effects. Unlike metronidazole, Tongkat Ali extracts appear to be effective against multiple Blastocystis spp. subtypes without requiring subtype identification, which could significantly streamline the diagnostic process [125].
Medicinal plants from Egypt have also been investigated for their anti-Blastocystis potential. Achillea fragrantissima (Forssk.) Sch. Bip. has demonstrated activity against ST1 and ST3 subtypes. At a concentration of 4000 µg/mL, its extracts induced morphological changes in Blastocystis spp., leading to complete protozoan destruction after 72 h [126]. Similarly, Origanum majorana L. and Foeniculum vulgare Mill. have shown antioxidant and antiparasitic properties, with O. majorana extract at 400 µg/mL exhibiting protozoicidal effects comparable to nitazoxanide at 500 µg/mL [127].
Additionally, several medicinal plants from Ghana have been reported to exhibit strong activity against Blastocystis spp., including Mallotus oppositifolius (Geiseler) Müll. Arg., which has shown efficacy comparable to metronidazole [128]. Ahmed et al. [129] further expanded the list of plants with cytotoxic effects on Blastocystis spp. by identifying Ptilostemon chamaepeuce subsp. cyprius, a species endemic to Cyprus, as a potential therapeutic candidate.
Dietary ingredients and spices have also been studied for their potential in Blastocystis spp. eradication. Extracts from garlic (Allium sativum L.), ginger (Zingiber officinale Rosc.), horseradish (Armoracia rusticana B. Mey et Scherb.), and turmeric (Curcuma longa L.) have shown varying degrees of efficacy against ST3 and ST7. Garlic and turmeric were the most effective against ST3, while turmeric and horseradish showed the greatest reduction in ST7 populations [130]. Garlic extracts, rich in thiosulfonates such as allicin, inhibit protein and nucleic acid synthesis in Blastocystis spp., significantly reducing parasite counts after 48 h of incubation, with effects comparable to metronidazole and nitazoxanide [131,132].
Hexahydrocurcumin, a bioactive compound found in ginger extracts, has been shown to possess protozoicidal properties [117]. Abdel-Hafeez et al. [133] reported that treatment with garlic and ginger extracts significantly reduced the number of Blastocystis spp. cysts excreted by mice compared to the control group. Both garlic and ginger are potent antioxidants that can inhibit the production of nitric oxide (NO), a compound whose persistently elevated levels during Blastocystis spp. infection contribute to intestinal barrier damage [117,133]. In contrast, black pepper (Piper nigrum L.) and white cumin (Trachyspermum ammi L.) are considered to have a more limited effect on Blastocystis spp., and further research is needed to assess their potential efficacy [132].
Drugs commonly used for other medical conditions may also aid in the eradication of protozoan infections. Basyoni et al. [134] investigated the efficacy of atorvastatin, a statin drug, in combating Blastocystis spp. infections. In addition to their cholesterol-lowering effects, statins have been suggested to protect intestinal barrier integrity by inhibiting specific enzymes [135]. Atorvastatin, administered at doses of 20–40 mg/kg, exhibited strong activity against Blastocystis spp., and when combined with metronidazole (10 mg/kg), it achieved a 98–99% reduction in parasite cell numbers [134].
Simeprevir, a serine protease inhibitor primarily used in the treatment of hepatitis C virus (HCV) infections, has also been studied for its potential anti-Blastocystis effects [136]. Serine proteases, which play a critical role in HCV maturation, are also involved in the regulation of proinflammatory cytokines during Blastocystis spp. infections [136,137]. Increasing concentrations of simeprevir were found to progressively inhibit the growth and viability of Blastocystis spp. The drug’s mechanism of action was attributed to the induction of cell membrane rupture, ultimately leading to necrotic cell death [136].

5.3. The Role of Probiotics in Therapy

Probiotics have been shown to reduce the number of parasites and alleviate symptoms associated with their colonization. Clinical studies support their use as adjunctive therapeutic agents in parasitic infections [138,139]. Probiotics are live microorganisms that, when consumed as part of the diet, can influence the composition of the gut microbiota [34]. Since Blastocystis spp. infections have been linked to gut microbiota imbalances, probiotic therapy may contribute to restoring microbial homeostasis [6].
Among the most studied probiotics for Blastocystis spp. infections is Saccharomyces boulardii, which has demonstrated effectiveness in treating gastrointestinal disorders with an inflammatory component [105,139]. Clinical research has confirmed its ability to alleviate symptoms such as diarrhea, vomiting, abdominal pain, and bloating in children infected with Blastocystis spp. [140]. Similar improvements were observed by Angelici et al. [141], who reported complete resolution of gastrointestinal symptoms in a patient following S. boulardii supplementation. Animal studies have further shown that live S. boulardii strains significantly reduce levels of proinflammatory cytokines (IL-6, IL-8, TNF-α) and inhibit the expression of inducible nitric oxide synthase (iNOS) in the colonic mucosa of rats infected with Blastocystis spp. [142]. Additionally, certain bacterial strains, including Lactobacillus rhamnosus, Lactococcus lactis, and Enterococcus faecium, have been found to inhibit the growth of Blastocystis ST3 [143].
Table 2. Natural plant extracts and probiotics as alternative treatment options against Blastocystis sp. infection.
Table 2. Natural plant extracts and probiotics as alternative treatment options against Blastocystis sp. infection.
NamePart UsedBlastocystisReference
SourceSubtypeForm Susceptible to the Treatments
Plants
Salvadora persica L.rootclinical isolate (gastrointestinal complaints)ST1, ST3, ST5 [122]
Boesenbergia rotunda (L.) Mansfrhizomeclinical isolateST3vacuolar forms[123]
Ganoderma lucidum (Fr.)fruiting body ST3
Eurycoma longifolia
(Tongkat Ali)		rootclinical isolateST1, ST3, ST5 [124]
Achillea fragrantissima (Forssk.) Sch. Bip.
(Qaysoom)		aerial partsclinical isolate (gastrointestinal symptoms)ST1, ST2vacuolar/granular forms[126]
Origanum majorana L.
(Marjoram)		leavesclinical isolate (diarrhea samples) cyst[127]
Foeniculum vulgare Mill.seeds
Mallotus oppositifolius (Geiseler) Müllcortex and radixclinical isolateST4 [128]
Ptilostemon chamaepeuce subsp. cypriusleavesclinical isolate (abdominal pain)ST1, ST1 and ST3 coinfectionvacuolar/granular forms[129]
Allium sativum L.
(Garlic)		clovesclinical isolate (symptomatic individuals:
ST3-intestinal methanogen overgrowth (IMO),
ST7-rectal cancer)		ST1 (x), ST7vacuolar forms[130]
Zingiber officinale Rosc.
(Ginger)		roots ST1, ST7 (x)
Armoracia rusticana Gaertn.
(Horseradish)		roots ST3
Curcuma longa L.
(Turmeric)		turmeric powder ST3 (x), ST7
Allium sativum L.
(Garlic)		fresh
bulbs of garlic		clinical isolate (patients with irritable bowel syndrome (IBS))ST1, ST1 and ST3 coinfectionvacuolar forms[132]
Allium sativum L.
(Garlic)		fresh peeled clovesmice infected with Blastocystis (experimental model) cyst[133]
Zingiber officinale Rosc.
(Ginger)		ginger powder
Probiotics
Saccharomyces boulardii clinical isolate (gastrointestinal symptoms) cyst
(S. boulardii has potential beneficial effects)		[140]
Lactobacillus rhamnosus cultureST3inhibition of Blastocystis proliferation by LAB[143]
Lactococcus lactis ST3
x—the highest inhibitory effect.
The mechanisms through which probiotics exert their effects are complex. Different probiotic strains, including bacterial and yeast-based probiotics, influence the immune system by modulating host immune responses [139]. Their interaction with intestinal epithelial and immune cells enhances the production of immunoglobulins IgA and IgM, strengthening mucosal immunity and reinforcing the barrier against pathogenic microorganisms [144,145]. S. boulardii has been shown to regulate cytokine levels, increasing the ratio of anti-inflammatory cytokines (IL-4, IL-10) to proinflammatory cytokines (IL-8, IL-1β), thereby reducing inflammation [146].
Another key probiotic mechanism involves microbial competition for ecological niches within the gut. Probiotics such as Lactobacillus spp. can deprive pathogens of essential nutrients by binding and transporting iron compounds, making them unavailable for pathogen growth [139]. Some probiotic species also produce bioactive compounds, including bacteriocins, organic acids, and hydrogen peroxide, which inhibit the survival and replication of pathogens in the gastrointestinal tract [139,147,148]. Lactobacillus reuteri produces reuterin (3-hydroxypropionaldehyde), a broad-spectrum antimicrobial agent effective against bacteria, viruses, yeasts, fungi, and protozoa [149]. Additionally, lactic acid bacteria inhibit acid-sensitive microorganisms by producing lactic acid, which lowers the local pH and disrupts pathogen metabolism [150]. S. boulardii secretes antimicrobial peptides of varying molecular weights that reduce pathogen adherence to the intestinal epithelium and neutralize microbial toxins [146].
Probiotics also contribute to gut health by modulating the synthesis of short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate. These metabolites play a crucial role in maintaining intestinal homeostasis and supporting key physiological and biochemical processes [146]. S. boulardii has been shown to restore normal SCFA levels, which are typically reduced during inflammatory conditions such as irritable bowel syndrome (IBS) [34,151,152].
The multifaceted effects of probiotics make them increasingly valuable as adjunctive treatments for various gastrointestinal disorders, with strong scientific evidence supporting their therapeutic efficacy. Their widespread availability in diverse formulations, including capsules, tablets, powders, drops, and pastes, allows for personalized treatment options based on patient age and preferences. Probiotics present a safe and promising alternative for managing pathogenic infections; however, excessive self-administration may lead to adverse effects, such as allergic reactions, sepsis, or endocarditis in individuals with severe gastrointestinal conditions. To minimize risks, it is essential to adhere to medical recommendations regarding dosage and duration of probiotic use. Further research is needed to refine our understanding of probiotic applications in human health and optimize their use in clinical practice [34,153,154].

6. Conclusions

The pathogenicity of Blastocystis spp. remains unresolved, and its virulence factors, pathogenic potential, and host-specific traits associated with symptomatic infections are still poorly understood.
  • This review highlights the often-overlooked association between Blastocystis spp. infections and gastrointestinal and autoimmune diseases. Patients with autoimmune disorders, where the immune system mistakenly attacks self-tissues, appear to be at a significantly higher risk of Blastocystis spp. infection compared to healthy individuals. Additionally, the increased prevalence of Blastocystis spp. in colorectal cancer (CRC) patients suggests a potential role in carcinogenesis, although further studies are necessary to confirm this hypothesis.
  • Symptomatic blastocystosis can manifest as chronic diarrhea, abdominal pain, nausea, vomiting, anorexia, weight loss, and general weakness. However, Blastocystis spp. infections are often characterized by nonspecific gastrointestinal symptoms, including diarrhea, irregular bowel movements, bloating, and abdominal discomfort. In contrast, patients with chronic urticaria rarely exhibit gastrointestinal symptoms.
  • The diagnosis of Blastocystis spp. infections still relies predominantly on microscopic methods, which are known for their low sensitivity. Therefore, a combination of direct microscopic examination and molecular techniques, particularly PCR, should be employed whenever possible to improve diagnostic accuracy.
  • Metronidazole remains the primary treatment for Blastocystis spp. infections, despite reports of treatment failure in some cases. When metronidazole proves ineffective, nitazoxanide may be considered as an alternative therapy.
  • Natural plant extracts and certain dietary components have demonstrated antiparasitic activity against Blastocystis spp. and may serve as adjunctive or alternative treatment options.

Author Contributions

The following represents the substantial contributions of individual authors: Conceptualization, O.P.-P. and N.Ł.-A.; methodology, O.P.-P.; data analysis, O.P.-P., D.K.-B. and K.G.; writing the manuscript, O.P.-P. and N.Ł.-A.; providing scientific supervision of manuscript, D.K.-B. and N.Ł.-A. All authors have read and agreed to the published version of the manuscript.

Funding

The Pomeranian Medical University in Szczecin provided financial support (WFB-431-02/S/12/2024). The funder had a role in the collection and analysis of data.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare that they have no competing interests.

References

  1. Parija, S.C.; Jeremiah, S. Blastocystis: Taxonomy, biology and virulence. Trop. Parasitol. 2013, 3, 17–25. [Google Scholar] [CrossRef] [PubMed]
  2. Rudzińska, M.; Kowalewska, B.; Sikorska, K. Diagnostyka laboratoryjna zarażeń Blastocystis—Wyzwania i kontrowersje. Diagn. Lab. 2020, 56, 27–34. [Google Scholar] [CrossRef]
  3. Badparva, E.; Kheirandish, F. Blastocystis hominis: A Pathogenic Parasite. Arch. Clin. Infect. Dis. 2020, 15, e97388. [Google Scholar] [CrossRef]
  4. Kosik-Bogacka, D.; Łanocha-Arendarczyk, N.; Korzeniewski, K.; Mularczyk, M.; Kabat-Koperska, J.; Ziętek, P.; Marchelek-Myśliwiec, M. Cryptosporidium spp. Infection in Adult Kidney Transplant Patients: A Systematic Review and Meta-Analysis. J. Clin. Med. 2024, 13, 6395. [Google Scholar] [CrossRef] [PubMed]
  5. Stensvold, C.R.; Tan, K.S.W.; Clark, C.G.  Blastocystis. Trends Parasitol. 2020, 36, 315–316. [Google Scholar] [CrossRef]
  6. Aykur, M.; Malatyalı, E.; Demirel, F.; Cömert-Koçak, B.; Gentekaki, E.; Tsaousis, A.D.; Dogruman-Al, F. Blastocystis: A Mysterious Member of the Gut Microbiome. Microorganisms 2024, 12, 461. [Google Scholar] [CrossRef]
  7. Skotarczak, B. Genetic diversity and pathogenicity of Blastocystis. Ann. Agric. Environ. Med. 2018, 25, 411–416. [Google Scholar] [CrossRef]
  8. Noël, C.; Dufernez, F.; Gerbod, D.; Edgcomb, V.P.; Delgado-Viscogliosi, P.; Ho, L.C.; Singh, M.; Wintjens, R.; Sogin, M.L.; Capron, M.; et al. Molecular phylogenies of Blastocystis isolates from different hosts: Implications for genetic diversity, identification of species, and zoonosis. J. Clin. Microbiol. 2005, 43, 348–355. [Google Scholar] [CrossRef] [PubMed]
  9. Wang, Y.; Lai, X.; Liu, R.; Li, J.; Ren, G.; Lu, X.; Wu, Y.; Khan, J.; Yu, X.; Qiang, Y.; et al. Molecular prevalence and subtype characteristics of Blastocystis among school children in Hainan, the tropical island province of China. Acta Trop. 2024, 258, 107353. [Google Scholar] [CrossRef]
  10. Jinatham, V.; Yowang, A.; Stensvold, C.R.; Michalopoulou, E.; Vichasilp, T.; Suwannahitatorn, P.; Popluechai, S.; Tsaousis, A.D.; Gentekaki, E. Blastocystis colonization and associations with population parameters in Thai adults. PLoS Negl. Trop. Dis. 2024, 18, e0012292. [Google Scholar] [CrossRef]
  11. Jiménez, P.; Muñoz, M.; Ramírez, J.D. An update on the distribution of Blastocystis subtypes in the Americas. Heliyon 2022, 8, e12592. [Google Scholar] [CrossRef] [PubMed]
  12. Duda, A.; Kosik-Bogacka, D.; Lanocha, N.; Szymański, S. Blastocystis hominis—Komensal czy patogen? [Blastocystis homini—parasites or commensals?]. Ann. Acad. Med. Stetin. 2014, 60, 23–28. [Google Scholar] [CrossRef] [PubMed]
  13. Rudzińska, M.; Sikorska, K. Epidemiology of Blastocystis Infection: A Review of Data from Poland in Relation to Other Reports. Pathogens 2023, 12, 1050. [Google Scholar] [CrossRef] [PubMed]
  14. Hublin, J.S.Y.; Maloney, J.G.; Santin, M. Blastocystis in domesticated and wild mammals and birds. Res. Vet. Sci. 2021, 135, 260–282. [Google Scholar] [CrossRef] [PubMed]
  15. Pietrzak-Makyła, B.; Korzeniewski, K.; Gładysz, P.; Lass, A. Detection and Molecular Characterization of Blastocystis Species in Polish Soldiers Stationed in the Republic of Kosovo. Int. J. Mol. Sci. 2023, 24, 14100. [Google Scholar] [CrossRef]
  16. Matovelle, C.; Tejedor, M.T.; Monteagudo, L.V.; Beltrán, A.; Quílez, J. Prevalence and Associated Factors of Blastocystis sp. Infection in Patients with Gastrointestinal Symptoms in Spain: A Case-Control Study. Trop. Med. Infect. Dis. 2022, 7, 226. [Google Scholar] [CrossRef]
  17. Fletcher, S.M.; Stark, D.; Harkness, J.; Ellis, J. Enteric protozoa in the developed world: A public health perspective. Clin. Microbiol. Rev. 2012, 25, 420–449. [Google Scholar] [CrossRef]
  18. Roberts, T.; Stark, D.; Harkness, J.; Ellis, J. Update on the pathogenic potential and treatment options for Blastocystis sp. Gut Pathog. 2014, 6, 17. [Google Scholar] [CrossRef]
  19. Asghari, A.; Sadeghipour, Z.; Hassanipour, S.; Abbasali, Z.; Ebrahimzadeh-Parikhani, H.; Hashemzaei, M.; Alimardani, V.; Hatam, G. Association between Blastocystis sp. infection and immunocompromised patients: A systematic review and meta-analysis. Environ. Sci. Pollut. Res. Int. 2021, 28, 60308–60328. [Google Scholar] [CrossRef]
  20. Khorshidvand, Z.; Khazaei, S.; Amiri, M.; Taherkhani, H.; Mirzaei, A. Worldwide prevalence of emerging parasite Blastocystis in immunocompromised patients: A systematic review and meta-analysis. Microb. Pathog. 2021, 152, 104615. [Google Scholar] [CrossRef]
  21. Zanetti, A.D.S.; Malheiros, A.F.; de Matos, T.A.; Longhi, F.G.; Moreira, L.M.; Silva, S.L.; Castrillon, S.K.I.; Ferreira, S.M.B.; Ignotti, E.; Espinosa, O.A. Prevalence of Blastocystis sp. infection in several hosts in Brazil: A systematic review and meta-analysis. Parasit. Vectors 2020, 13, 30. [Google Scholar] [CrossRef] [PubMed]
  22. Abdel-Hafeez, E.H.; Ahmad, A.K.; Abdelgelil, N.H.; Abdellatif, M.Z.; Kamal, A.M.; Hassanin, K.M.; Abdel-Razik, A.R.; Abdel-Raheem, E.M. Immunopathological assessments of human Blastocystis spp. in experimentally infected immunocompetent and immunosuppresed mice. Parasitol. Res. 2016, 115, 2061–2071. [Google Scholar] [CrossRef]
  23. Wawrzyniak, I.; Poirier, P.; Viscogliosi, E.; Dionigia, M.; Texier, C.; Delbac, F.; Alaoui, H.E. Blastocystis, an unrecognized parasite: An overview of pathogenesis and diagnosis. Ther. Adv. Infect. Dis. 2013, 1, 167–178. [Google Scholar] [CrossRef] [PubMed]
  24. Chen, C.H.; Sun, H.Y.; Chien, H.F.; Lai, H.S.; Chou, N.K. Blastocystis hominis infection in a post-cardiotomy patient on extracorporeal membrane oxygenation support: A case report and literature review. Int. J. Surg. Case Rep. 2014, 5, 637–639. [Google Scholar] [CrossRef]
  25. Stenzel, D.J.; Boreham, P.F. Blastocystis hominis revisited. Clin. Microbiol. Rev. 1996, 9, 563–584. [Google Scholar] [CrossRef] [PubMed]
  26. Khademvatan, S.; Masjedizadeh, R.; Yousefi-Razin, E.; Mahbodfar, H.; Rahim, F.; Yousefi, E.; Foroutan, M. PCR-based molecular characterization of Blastocystis hominis subtypes in southwest of Iran. J. Infect. Public Health 2018, 11, 43–47. [Google Scholar] [CrossRef] [PubMed]
  27. Ligero-López, J.; García-Rodríguez, J.; Ruiz-Carrascoso, G. Diagnosis of gastrointestinal infections: Comparison between traditional microbiology and a commercial syndromic molecular-based panel. FEMS Microbiol. Lett. 2023, 370, fnad122. [Google Scholar] [CrossRef]
  28. Sari, I.P.; Benung, M.R.; Wahdini, S.; Kurniawan, A. Diagnosis and Identification of Blastocystis Subtypes in Primary School Children in Jakarta. J. Trop. Pediatr. 2018, 64, 208–214. [Google Scholar] [CrossRef] [PubMed]
  29. Ragavan, N.D.; Kumar, S.; Chye, T.T.; Mahadeva, S.; Shiaw-Hooi, H. Blastocystis sp. in Irritable Bowel Syndrome (IBS)—Detection in Stool Aspirates during Colonoscopy. PLoS ONE 2015, 10, e0121173. [Google Scholar] [CrossRef]
  30. Kumarasamy, V.; Atroosh, W.M.; Anbazhagan, D.; Abdalla, M.M.I.; Azzani, M. Association of Blastocystis hominis with colorectal cancer: A systematic review of in vitro and in vivo evidences. World J. Gastrointest. Oncol. 2022, 14, 734–745. [Google Scholar] [CrossRef]
  31. Kesuma, Y.; Firmansyah, A.; Bardosono, S.; Sari, I.P.; Kurniawan, A. Blastocystis ST-1 is associated with Irritable Bowel Syndrome-diarrhoea (IBS-D) in Indonesian adolescences. Parasite Epidemiol. Control 2019, 6, e00112. [Google Scholar] [CrossRef]
  32. Kök, M.; Çekin, Y.; Çekin, A.H.; Uyar, S.; Harmandar, F.; Şahintürk, Y. The role of Blastocystis hominis in the activation of ulcerative colitis. Turk. J. Gastroenterol. 2019, 30, 40–46. [Google Scholar] [CrossRef] [PubMed]
  33. El-Zawawy, H.T.; Farag, H.F.; Tolba, M.M.; Abdalsamea, H.A. Improving Hashimoto’s thyroiditis by eradicating Blastocystis hominis: Relation to IL-17. Ther. Adv. Endocrinol. Metab. 2020, 11, 2042018820907013. [Google Scholar] [CrossRef] [PubMed]
  34. Ahlawat, G.M.; Singh, P.K. Methods of Determining Irritable Bowel Syndrome and Efficiency of Probiotics in Treatment: A Review. Curr. Ther. Res. Clin. Exp. 2023, 99, 100721. [Google Scholar] [CrossRef] [PubMed]
  35. Lepczyńska, M.; Dzika, E.; Kubiak, K.; Korycińska, J. The role of Blastocystis sp. as an etiology of irritable bowel syndrome. Pol. Ann. Med. 2016, 23, 57–60. [Google Scholar] [CrossRef]
  36. Olyaiee, A.; Sadeghi, A.; Yadegar, A.; Mirsamadi, E.S.; Mirjalali, H. Gut Microbiota Shifting in Irritable Bowel Syndrome: The Mysterious Role of Blastocystis sp. Front. Med. 2022, 9, 890127. [Google Scholar] [CrossRef]
  37. Berumen, A.; Lennon, R.; Breen-Lyles, M.; Griffith, J.; Patel, R.; Boxrud, D.; Decuir, M.; Farrugia, G.; Smith, K.; Grover, M.; et al. Characteristics and risk factors of post-infection irritable bowel syndrome after Campylobacter enteritis. Clin. Gastroenterol. Hepatol. 2021, 19, 1855–1863.e1851. [Google Scholar] [CrossRef]
  38. Ianiro, G.; Tilg, H.; Gasbarrini, A. Antibiotics as deep modulators of gut microbiota: Between good and evil. Gut 2016, 65, 1906–1915. [Google Scholar] [CrossRef]
  39. Das, R.; Khalil, S.; Mirdha, B.R.; Makharia, G.K.; Dattagupta, S.; Chaudhry, R. Molecular characterization and subtyping of Blastocystis species in irritable bowel syndrome patients from north india. PLoS ONE 2016, 11, e0147055. [Google Scholar] [CrossRef]
  40. Yakoob, J.; Jafri, W.; Jafri, N.; Khan, R.; Islam, M.; Beg, M.A.; Zaman, V. Irritable bowel syndrome: In search of an etiology: Role of Blastocystis hominis. Am. J. Trop. Med. Hyg. 2004, 70, 383–385. [Google Scholar] [CrossRef]
  41. Surangsrirat, S.; Thamrongwittawatpong, L.; Piyaniran, W.; Naaglor, T.; Khoprasert, C.; Taamasri, P.; Mungthin, M.; Saovanee, L. Assessment of the association between Blastocystis infection and irritable bowel syndrome. J. Med. Assoc. Thail. 2010, 93 (Suppl. S6), S119–S124. [Google Scholar]
  42. Jadallah, K.A.; Nimri, L.F.; Ghanem, R.A. Protozoan parasites in irritable bowel syndrome: A case-control study. World J. Gastrointest. Pharmacol. Ther. 2017, 8, 201–207. [Google Scholar] [CrossRef] [PubMed]
  43. Ibrahim, A.N.; Al-Ashkar, A.M.; Nazeer, J.T. Additional Glance on the Role of Dientamoeba fragilis & Blastocystis hominis in Patients with Irritable Bowel Syndrome. Iran. J. Parasitol. 2018, 13, 100–107. [Google Scholar] [PubMed]
  44. Nahhas, S.A. Blastocystis sp.: Frequency and typing among Irritable Bowel Syndrome (IBS) patients. J. Clin. Med. 2024, 5, 1–7. [Google Scholar] [CrossRef]
  45. Beatty, J.K.; Bhargava, A.; Buret, A.G. Post-infectious irritable bowel syndrome: Mechanistic insights into chronic disturbances following enteric infection. World J. Gastroenterol. 2014, 20, 3976–3985. [Google Scholar] [CrossRef]
  46. Motomura, Y.; Khan, W.I.; El-Sharkawy, R.T.; Verma-Gandhu, M.; Grencis, R.K.; Collins, S.M. Mechanisms underlying gut dysfunction in a murine model of chronic parasitic infection. Am. J. Physiol. Gastrointest. Liver Physiol. 2010, 299, G1354–G1360. [Google Scholar] [CrossRef] [PubMed]
  47. Troeger, H.; Epple, H.J.; Schneider, T.; Wahnschaffe, U.; Ullrich, R.; Burchard, G.D.; Jelinek, T.; Zeitz, M.; Fromm, M.; Schulzke, J.-D. Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in human duodenum. Gut 2007, 56, 328–335. [Google Scholar] [CrossRef] [PubMed]
  48. Venkova, K.; Greenwood-van Meerveld, B. Long-lasting changes in small intestinal transport following the recovery from Trichinella spiralis infection. Neurogastroenterol. Motil. 2006, 18, 234–242. [Google Scholar] [CrossRef] [PubMed]
  49. McShane, A.; Bath, J.; Jaramillo, A.M.; Ridley, C.; Walsh, A.A.; Evans, C.M.; Thornton, D.J.; Ribbeck, K. Mucus. Curr. Biol. 2021, 31, R938–R945. [Google Scholar] [CrossRef]
  50. Ismail, M.H.; Molan, A.L.; Abbas, S.K. Serological levels of cytokines in irritable bowel syndrome (IBS) patients and non-IBS subjects with and without Blastocystis spp. infection. Ann. Parasitol. 2022, 68, 77–85. [Google Scholar] [CrossRef]
  51. Olivo-Diaz, A.; Romero-Valdovinos, M.; Gudiño-Ramirez, A.; Reyes-Gordillo, J.; Jimenez-Gonzalez, D.E.; Ramirez-Miranda, M.E.; Martinez-Flores, W.A.; Martinez-Hernandez, F.; Flisser, A.; Maravilla, P. Findings related toIL-8 and IL-10 gene polymorphisms in a Mexican patient population with irritable bowel syndrome infected with Blastocystis. Parasitol. Res. 2012, 111, 487–491. [Google Scholar] [CrossRef] [PubMed]
  52. Hussain, R.; Jaferi, W.; Zuberi, S.; Baqai, R.; Abrar, N.; Ahmed, A.; Zaman, V. Significantly increased IgG2 subclass antibody levels to Blastocystis hominis in patients with irritable bowel syndrome. Am. J. Trop. Med. Hyg. 1997, 56, 301–306. [Google Scholar] [CrossRef] [PubMed]
  53. Wang, L.; Alammar, N.; Singh, R.; Nanavati, J.; Song, Y.; Chaudhary, R.; Mullin, G.E. Gut Microbial Dysbiosis in the Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Case-Control Studies. J. Acad. Nutr. Diet. 2020, 120, 56–586. [Google Scholar] [CrossRef]
  54. Yason, J.A.; Liang, Y.R.; Png, C.W.; Zhang, Y.; Tan, K.S.W. Interactions between a pathogenic Blastocystis subtype and gut microbiota: In vitro and in vivo studies. Microbiome 2019, 7, 30. [Google Scholar] [CrossRef]
  55. Yañez, C.M.; Hernández, A.M.; Sandoval, A.M.; Domínguez, M.A.M.; Muñiz, S.A.Z.; Gómez, J.O.G. Prevalence of Blastocystis and its association with Firmicutes/Bacteroidetes ratio in clinically healthy and metabolically ill subjects. BMC Microbiol. 2021, 21, 339. [Google Scholar] [CrossRef]
  56. Vega, L.; Herrera, G.; Muñoz, M.; Patarroyo, M.A.; Ramírez, J.D. Occurrence of Blastocystis in Patients with Clostridioides difficile Infection. Pathogens 2020, 9, 283. [Google Scholar] [CrossRef]
  57. Azimirad, M.; Gol, S.M.A.; Javanmard, E.; Mirjalali, H.; Yadegar, A.; Aghdaei, H.A.; Shahrokh, S.; Balaii, H.; Sadeghi, A.; Zali, M.R. Blastocystis and Clostridioides difficile: Evidence for a Synergistic Role in Colonization Among IBD Patients with Emphasis on Ulcerative Colitis. Turk. J. Gastroenterol. 2021, 32, 500–507. [Google Scholar] [CrossRef]
  58. Salvador, F.; Lobo, B.; Goterris, L.; Alonso-Cotoner, C.; Santos, J.; Sulleiro, E.; Bailo, B.; Carmena, D.; Sánchez-Montalvá, A.; Bosch-Nicolau, P.; et al. Blastocystis sp. Carriage and Irritable Bowel Syndrome: Is the Association Already Established? Biology 2021, 10, 340. [Google Scholar] [CrossRef]
  59. Khademvatan, S.; Masjedizadeh, R.; Rahim, F.; Mahbodfar, H.; Salehi, R.; Yousefi-Razin, E.; Foroutan, M. Blastocystis and irritable bowel syndrome: Frequency and subtypes from Iranian patients. Parasitol. Int. 2017, 66, 142–145. [Google Scholar] [CrossRef]
  60. Yu, B.; Kang, J.; Lei, H.; Li, Z.; Yang, H.; Zhang, M. Immunotherapy for colorectal cancer. Front. Immunol. 2024, 15, 1433315. [Google Scholar] [CrossRef]
  61. Taghipour, A.; Rayatdoost, E.; Bairami, A.; Bahadory, S.; Abdoli, A. Are Blastocystis hominis and Cryptosporidium spp. playing a positive role in colorectal cancer risk? A systematic review and meta-analysis. Infect. Agent. Cancer 2022, 17, 32. [Google Scholar] [CrossRef] [PubMed]
  62. Sulżyc-Bielicka, V.; Kołodziejczyk, L.; Adamska, M.; Skotarczak, B.; Jaczewska, S.; Safranow, K.; Bielicki, P.; Kładny, J.; Bielicki, D. Colorectal cancer and Blastocystis sp. infection. Parasit. Vectors 2021, 14, 200. [Google Scholar] [CrossRef] [PubMed]
  63. Sayed, I.M.; Ramadan, H.K.-A.; El-Mokhtar, M.A.; Abdel-Wahid, L. Microbiome and gastrointestinal malignancies. Curr. Opin. Physiol. 2021, 22, 100451. [Google Scholar] [CrossRef]
  64. Tocci, S.; Das, S.; Sayed, I.M. An Update on Blastocystis: Possible Mechanisms of Blastocystis-Mediated Colorectal Cancer. Microorganisms 2024, 12, 1924. [Google Scholar] [CrossRef]
  65. Ali, S.H.; Ismail, M.A.M.; El-Badry, A.A.; Abu-Sarea, E.Y.; Dewidar, A.M.; Hamdy, D.A. An Association Between Blastocystis Subtypes and Colorectal Cancer Patients: A Significant Different Profile from Non-cancer Individuals. Acta Parasitol. 2022, 67, 752–763. [Google Scholar] [CrossRef] [PubMed]
  66. Mohamed, A.M.; Ahmed, M.A.; Ahmed, S.A.; Al-Semany, S.A.; Alghamdi, S.S.; Zaglool, D.A. Predominance and association risk of Blastocystis hominis subtype I in colorectal cancer: A case control study. Infect. Agent. Cancer 2017, 12, 21. [Google Scholar] [CrossRef] [PubMed]
  67. Tito, R.Y.; Chaffron, S.; Caenepeel, C.; Lima-Mendez, G.; Wang, J.; Vieira-Silva, S.; Falony, G.; Hildebrand, F.; Darzi, Y.; Rymenans, L.; et al. Population-level analysis of Blastocystis subtype prevalence and variation in the human gut microbiota. Gut 2019, 68, 1180–1189. [Google Scholar] [CrossRef]
  68. Kumarasamy, V.; Roslani, A.C.; Rani, K.U.; Kumar Govind, S. Advantage of using colonic washouts for Blastocystis detection in colorectal cancer patients. Parasit. Vectors 2014, 7, 162. [Google Scholar] [CrossRef]
  69. Hawash, Y.A.; Ismail, K.A.; Saber, T.; Eed, E.M.; Khalifa, A.S.; Alsharif, K.F.; Alghamdi, S.A.; Dahlawi, H.A.; Alsanie, W.; Khalifa, A.M.; et al. Predominance of Infection with Blastocystis hominis in Patients with Colorectal Cancer and Its Association with High Mucin Content, Infiltration of Inflammatory Cells and Elevated Serum Tumor Necrosis Factor α. Infect. Dis. Clin. Pract. 2021, 29, e32–e38. [Google Scholar] [CrossRef]
  70. Kumarasamy, V.; Kuppusamy, U.R.; Jayalakshmi, P.; Samudi, C.; Ragavan, N.D.; Kumar, S. Exacerbation of coloncarcinogenesis by Blastocystis sp. PLoS ONE 2017, 12, e0183097. [Google Scholar] [CrossRef]
  71. Chandramathi, S.; Suresh, K.; Kuppusamy, U.R. Solubilized antigen of Blastocystis hominis facilitates the growth of human colorectal cancer cells, HCT116. Parasitol. Res. 2010, 106, 941–945. [Google Scholar] [CrossRef] [PubMed]
  72. Bian, B.; Mongrain, S.; Cagnol, S.; Langlois, M.J.; Boulanger, J.; Bernatchez, G.; Carrier, J.C.; Boudreau, F.; Rivard, N. Cathepsin B promotes colorectal tumorigenesis, cell invasion, and metastasis. Mol. Carcinog. 2016, 55, 671–687. [Google Scholar] [CrossRef] [PubMed]
  73. Mirza, H.; Wu, Z.; Kidwai, F.; Tan, K.S. A metronidazole-resistant isolate of Blastocystis spp. is susceptible to nitric oxide and downregulates intestinal epithelial inducible nitric oxide synthase by a novel parasite survival mechanism. Infect. Immun. 2011, 79, 5019–5026. [Google Scholar] [CrossRef] [PubMed]
  74. Wu, Z.; Mirza, H.; Tan, K.S. Intra-subtype variation in enteroadhesion accounts for differences in epithelial barrier disruption and is associated with metronidazole resistance in Blastocystis subtype-7. PLoS Negl. Trop. Dis. 2014, 8, e2885. [Google Scholar] [CrossRef]
  75. Ngo, P.A.; Neurath, M.F.; López-Posadas, R. Impact of Epithelial Cell Shedding on Intestinal Homeostasis. Int. J. Mol. Sci. 2022, 23, 4160. [Google Scholar] [CrossRef]
  76. Puthia, M.K.; Lu, J.; Tan, K.S. Blastocystis ratti contains cysteine proteases that mediate interleukin-8 response from human intestinal epithelial cells in an NF-kappaB-dependent manner. Eukaryot. Cell 2008, 7, 435–443. [Google Scholar] [CrossRef] [PubMed]
  77. Kumarasamy, V.; Kuppusamy, U.R.; Samudi, C.; Kumar, S. Blastocystis sp. subtype 3 triggers higher proliferation of human colorectal cancer cells, HCT116. Parasitol. Res. 2013, 112, 3551–3555. [Google Scholar] [CrossRef] [PubMed]
  78. Wójcik, P.; Gęgotek, A.; Žarković, N.; Skrzydlewska, E. Oxidative Stress and Lipid Mediators Modulate Immune Cell Functions in Autoimmune Diseases. Int. J. Mol. Sci. 2021, 22, 723. [Google Scholar] [CrossRef]
  79. Lenti, M.V.; Rossi, C.M.; Melazzini, F.; Gastaldi, M.; Bugatti, S.; Rotondi, M.; Bianchi, P.I.; Gentile, A.; Chiovato, L.; Montecucco, C.; et al. Seronegative autoimmune diseases: A challenging diagnosis. Autoimmun. Rev. 2022, 21, 103143. [Google Scholar] [CrossRef]
  80. Sener, A.G.; Afsar, I. Infection and autoimmune disease. Rheumatol. Int. 2012, 32, 3331–3338. [Google Scholar] [CrossRef]
  81. Miyauchi, E.; Shimokawa, C.; Steimle, A.; Desai, M.S.; Ohno, H. The impact of the gut microbiome on extra-intestinal autoimmune diseases. Nat. Rev. Immunol. 2023, 23, 9–23. [Google Scholar] [CrossRef]
  82. Rajič, B.; Arapović, J.; Raguž, K.; Bošković, M.; Babić, S.M.; Maslać, S. Eradication of Blastocystis hominis prevents the development of symptomatic Hashimoto’s thyroiditis: A case report. J. Infect. Dev. Ctries. 2015, 9, 788–791. [Google Scholar] [CrossRef]
  83. Esfahanian, F.; Ghelich, R.; Rashidian, H.; Jadali, Z. Increased Levels of Serum Interleukin-17 in Patients with Hashimoto’s Thyroiditis. Indian J. Endocrinol. Metab. 2017, 21, 551–554. [Google Scholar] [CrossRef] [PubMed]
  84. Vargas-Uricoechea, H. Molecular Mechanisms in Autoimmune Thyroid Disease. Cells 2023, 12, 918. [Google Scholar] [CrossRef] [PubMed]
  85. Bahrami, F.; Babaei, E.; Badirzadeh, A.; Riabi, T.R.; Abdoli, A. Blastocystis, urticaria, and skin disorders: Review of the current evidences. Eur. J. Clin. Microbiol. Infect. Dis. 2020, 39, 1027–1042. [Google Scholar] [CrossRef] [PubMed]
  86. Vezir, S.; Kaya, F.; Vezir, E.; Karaosmanoğlu, N.; Adiloğlu, A.K. Evaluation of intestinal parasites in patients with chronic spontaneous urticaria in a territory hospital in Turkey. J. Infect. Dev. Ctries. 2019, 13, 927–932. [Google Scholar] [CrossRef] [PubMed]
  87. Jafari, A.; Bahrami, F.; Nasiri-Kalmarzi, R.; Abdoli, A. Chronic urticaria associated with Blastocystis hominis infection. Arch. Dermatol. Res. 2024, 316, 413. [Google Scholar] [CrossRef]
  88. Aykur, M.; Camyar, A.; Türk, B.G.; Sin, A.Z.; Dagci, H. Evaluation of association with subtypes and alleles of Blastocystis with chronic spontaneous urticaria. Acta Trop. 2022, 231, 106455. [Google Scholar] [CrossRef]
  89. Zuel-Fakkar, N.M.; Abdel Hameed, D.M.; Hassanin, O.M. Study of Blastocystis hominis isolates in urticaria: A case-control study. Clin. Exp. Dermatol. 2011, 36, 908–910. [Google Scholar] [CrossRef]
  90. Lepczyńska, M.; Chen, W.C.; Dzika, E. Mysterious chronic urticaria caused by Blastocystis spp.? Int. J. Dermatol. 2016, 55, 259–266, quiz 263–4, 266. [Google Scholar] [CrossRef]
  91. Gandomkar, M.; Fouladvand, M.; Malekizadeh, H.; Rayani, M.; Ahmadi, B.; Shadvar, N.; Sahebani, A.; Gharibi, N.K.; Barazesh, A. Prevalence of Blastocystis in Patients Referred to Bushehr Medical Centers and Its Relationship with Urticaria. Turk. Parazitol. Derg. 2024, 48, 77–81. [Google Scholar] [CrossRef]
  92. Beyhan, Y.E.; Güven, İ.; Aydın, M. Detection of Blastocystis sp. in ulcerative colitis, Crohn’s and chronic diarrheal patients by microscopy, culture and real-time polymerase chain reaction. Microb. Pathog. 2023, 177, 106039. [Google Scholar] [CrossRef] [PubMed]
  93. Unalan-Altintop, T.; Vahabov, C.; Ergunay, K.; Kurt, O.; Kav, T.; Akyon, Y.; Erguven, S. Investigation of Dientamoeba fragilis and Blastocystis in patients from Turkey with ulcerative colitis and irritable bowel syndrome: Any relation with genotypes? Acta Trop. 2022, 231, 106451. [Google Scholar] [CrossRef] [PubMed]
  94. Rossen, N.G.; Bart, A.; Verhaar, N.; van Nood, E.; Kootte, R.; de Groot, P.F.; D’Haens, G.R.; Ponsioen, C.Y.; van Gool, T. Low prevalence of Blastocystis sp. in active ulcerative colitis patients. Eur. J. Clin. Microbiol. Infect. Dis. 2015, 34, 1039–1044. [Google Scholar] [CrossRef]
  95. Keshawy, M.; Alabbassy, M. Systemic Lupus Erythematosus and Irritable Bowel Syndrome: Is Blastocystis hominis the Missing Piece of the Puzzle. Suez Canal Univ. Med. J. 2018, 21, 88–98. [Google Scholar] [CrossRef]
  96. Hernández, P.C.; Morales, L.; Chaparro-Olaya, J.; de Avila, J.; Bautista-Molano, W.; Bello-Gualtero, J.; Beltrán-Ostos, A.; Romero-Sánchez, C. Frequency and distribution of Blastocystis sp. subtypes in patients with spondyloarthritis in Bogotá, Colombia. Parasite Epidemiol. Control 2021, 15, e00227. [Google Scholar] [CrossRef] [PubMed]
  97. Soleimani Jevinani, S.; Mohammad Rahimi, H.; Asri, N.; Rostami-Nejad, M.; Ahmadipour, S.; Mirjalali, H. Molecular epidemiology and subtyping of Blastocystis sp. and its subtypes in celiac patients; a case control study. Microb. Pathog. 2023, 179, 106086. [Google Scholar] [CrossRef]
  98. Mahmoud, A.M.; Ismail, K.A.; Khalifa, O.M.; Abdel-wahab, M.M.; Hagag, H.M.; Mahmoud, M.K. Molecular Identification of Blastocystis hominis Isolates in Patients with Autoimmune Diseases. Appl. Microbiol. 2023, 3, 417–428. [Google Scholar] [CrossRef]
  99. Cekin, A.H.; Cekin, Y.; Adakan, Y.; Tasdemir, E.; Koclar, F.G.; Yolcular, B.O. Blastocystosis in patients with gastrointestinal symptoms: A case–control study. BMC Gastroenterol. 2012, 12, 122. [Google Scholar] [CrossRef]
  100. Coskun, A.; Malatyali, E.; Ertabaklar, H.; Yasar, M.B.; Karaoglu, A.O.; Ertug, S. Blastocystis in ulcerative colitis patients: Genetic diversity and analysis of laboratory findings. Asian Pac. J. Trop. Med. 2016, 9, 916–919. [Google Scholar] [CrossRef]
  101. El-Badry, A.A.; Abd El Wahab, W.M.; Hamdy, D.A.; Aboud, A. Blastocystis subtypes isolated from irritable bowel syndrome patients and co-infection with Helicobacter pylori. Parasitol. Res. 2018, 117, 127–137. [Google Scholar] [CrossRef] [PubMed]
  102. Mızrak, M.; Sarzhanov, F.; Demirel, F.; Dinç, B.; Filik, L.; Dogruman-Al, F. Detection of Blastocystis sp. and Dientamoeba fragilis using conventional and molecular methods in patients with celiac disease. Parasitol. Int. 2024, 101, 102888. [Google Scholar] [CrossRef]
  103. Labania, L.; Zoughbor, S.; Ajab, S.; Olanda, M.; Shantour, S.N.M.; Al Rasbi, Z. The associated risk of Blastocystis infection in cancer: A case control study. Front. Oncol. 2023, 13, 1115835. [Google Scholar] [CrossRef] [PubMed]
  104. Stensvold, C.R.; Smith, H.V.; Nagel, R.; Olsen, K.E.; Traub, R.J. Eradication of Blastocystis carriage with antimicrobials: Reality or delusion? J. Clin. Gastroenterol. 2010, 44, 85–90. [Google Scholar] [CrossRef] [PubMed]
  105. Sekar, U.; Shanthi, M. Blastocystis: Consensus of treatment and controversies. Trop. Parasitol. 2013, 3, 35–39. [Google Scholar] [CrossRef] [PubMed]
  106. Moghaddam, D.D.; Ghadirian, E.; Azami, M. Blastocystis hominis and the evaluation of efficacy of metronidazole and trimethoprim/sulfamethoxazole. Parasitol. Res. 2005, 96, 273–275. [Google Scholar] [CrossRef]
  107. Cassano, N.; Scoppio, B.M.; Loviglio, M.C.; Vena, G.A. Remission of delayed pressure urticaria after eradication of Blastocystis hominis. Acta Derm. Venereol. 2005, 85, 357–358. [Google Scholar] [CrossRef]
  108. Gupta, R.; Parsi, K. Chronic urticaria due to Blastocystis hominis. Australas. J. Dermatol. 2006, 47, 117–119. [Google Scholar] [CrossRef] [PubMed]
  109. Lucía, J.F.; Aguilar, C.; Betran, A. Blastocystis hominis colitis in a haemophilic patient as a cause of lower gastrointestinal bleeding. Haemophilia 2007, 13, 224–225. [Google Scholar] [CrossRef]
  110. Katsarou-Katsari, A.; Vassalos, C.M.; Tzanetou, K.; Spanakos, G.; Papadopoulou, C.; Vakalis, N. Acute urticaria associated with amoeboid forms of Blastocystis sp. subtype 3. Acta Derm. Venereol. 2008, 88, 80–81. [Google Scholar] [CrossRef]
  111. Batista, L.; Pérez Jove, J.; Rosinach, M.; Gonzalo, V.; Sainz, E.; Loras, C.; Forné, M.; Esteve, M.; Fernández-Bañares, F. Low efficacy of metronidazole in the eradication of Blastocystis hominis in symptomatic patients: Case series and systematic literature review. Gastroenterol. Hepatol. 2017, 40, 381–387. [Google Scholar] [CrossRef] [PubMed]
  112. Haresh, K.; Suresh, K.; Khairul Anus, A.; Saminathan, S. Isolate resistance of Blastocystis hominis to metronidazole. Trop. Med. Int. Health 1999, 4, 274–277. [Google Scholar] [CrossRef] [PubMed]
  113. Zaki, M.; Zaman, V.; Sheikh, N.A. Resistance of Blastocystis hominis cysts to chlorine. J. Pak. Med. Assoc. 1996, 46, 178–179. [Google Scholar]
  114. Roberts, T.; Bush, S.; Ellis, J.; Harkness, J.; Stark, D. In Vitro Antimicrobial Susceptibility Patterns of Blastocystis. Antimicrob. Agents Chemother. 2015, 59, 4417–4423. [Google Scholar] [CrossRef] [PubMed]
  115. Ahmed, F. A Review on HPLC Method Development and Validation of Metronidazole Tablet; ResearchGate GmbH: Berlin, Germany, 2021. [Google Scholar]
  116. Townson, S.M.; Upcroft, J.A.; Upcroft, P. Characterisation and purification of pyruvate:ferredoxin oxidoreductase from Giardia duodenalis. Mol. Biochem. Parasitol. 1996, 79, 183–193. [Google Scholar] [CrossRef] [PubMed]
  117. Hernández Ceruelos, A.; Romero-Quezada, L.C.; Ruvalcaba Ledezma, J.C.; López Contreras, L. Therapeutic uses of metronidazole and its side effects: An update. Eur. Rev. Med. Pharmacol. Sci. 2019, 23, 397–401. [Google Scholar] [CrossRef] [PubMed]
  118. Lepczyńska, M.; Białkowska, J.; Dzika, E.; Piskorz-Ogórek, K.; Korycińska, J. Blastocystis: How do specific diets and human gut microbiota affect its development and pathogenicity? Eur. J. Clin. Microbiol. Infect. Dis. 2017, 36, 1531–1540. [Google Scholar] [CrossRef]
  119. Rajamanikam, A.; Hooi, H.S.; Kudva, M.; Samudi, C.; Kumar, S. Resistance towards metronidazole in Blastocystis sp.: A pathogenic consequence. PLoS ONE 2019, 14, e0212542. [Google Scholar] [CrossRef]
  120. Kick, G.; Rueff, F.; Przybilla, B. Palmoplantar pruritus subsiding after Blastocystis hominis eradication. Acta Derm. Venereol. 2002, 82, 60. [Google Scholar] [CrossRef]
  121. Mirza, H.; Teo, J.D.; Upcroft, J.; Tan, K.S. A rapid, high-throughput viability assay for Blastocystis spp. reveals metronidazole resistance and extensive subtype-dependent variations in drug susceptibilities. Antimicrob. Agents Chemother. 2011, 55, 637–648. [Google Scholar] [CrossRef]
  122. El-Bali, M.A.; Abdulhakim, A.; Mohamed, R.T.; El-Malky, M.A.; Bakri, R.A.; Al-Harthi, S.A. Antiprotozoal potential of Salvadora persica against three virulent subtypes of Blastocystis sp. J. Parasit. Dis. 2020, 44, 694–701. [Google Scholar] [CrossRef] [PubMed]
  123. Kaewjai, C.; Tonsomboon, A.; Pawiwongchai, J.; Prommano, A.O. Antiprotozoal activity of Boesenbergia rotunda (L.) Mansf and Ganoderma lucidum (Fr.) Kart extracts against Blastocystis hominis. Vet. World 2023, 16, 187–193. [Google Scholar] [CrossRef] [PubMed]
  124. Girish, S.; Kumar, S.; Aminudin, N. Tongkat Ali (Eurycoma longifolia): A possible therapeutic candidate against Blastocystis sp. Parasit. Vectors 2015, 8, 332. [Google Scholar] [CrossRef] [PubMed]
  125. Girish, S.; Kumar, S.; Aminudin, N.; Hashim, N.M. Comparison of apoptotic responses in Blastocystis sp. upon treatment with Tongkat Ali and Metronidazole. Sci. Rep. 2021, 11, 7833. [Google Scholar] [CrossRef]
  126. Mokhtar, A.B.; Ahmed, S.A.; Eltamany, E.E.; Karanis, P. Anti-Blastocystis Activity In Vitro of Egyptian Herbal Extracts (Family: Asteraceae) with Emphasis on Artemisia judaica. Int. J. Environ. Res. Public Health 2019, 16, 1555. [Google Scholar] [CrossRef] [PubMed]
  127. Méabed, E.M.H.; El-Sayed, N.M.; Abou-Sreea, A.I.B.; Roby, M.H.H. Chemical analysis of aqueous extracts of Origanum majorana and Foeniculum vulgare and their efficacy on Blastocystis spp. cysts. Phytomedicine 2018, 43, 158–163. [Google Scholar] [CrossRef] [PubMed]
  128. Bremer Christensen, C.J.; Stensvold, C.R.; Jäger, A.K. Activity of medicinal plants from Ghana against the parasitic gut protist Blastocystis. J. Ethnopharmacol. 2015, 174, 569–575. [Google Scholar] [CrossRef]
  129. Ahmed, S.A.A.; Schou, C.; Mokhtar, A.B.; Karanis, P.; Gad, S.E.M. Blastocystis species growth inhibition in vitro by plant extracts. Microb. Pathog. 2024, 196, 106970. [Google Scholar] [CrossRef]
  130. Kot, K.; Michaliszyn, A.; Kalisińska, E.; Lepczyńska, M. The influence of plant extracts on viability of ST3 and ST7 subtypes of Blastocystis sp. Gut Pathog. 2024, 16, 19. [Google Scholar] [CrossRef]
  131. Abdel-Hafeez, E.H.; Ahmad, A.K.; Andelgelil, N.H.; Abdellatif, M.Z.; Kamal, A.M.; Mohamed, R.M. In vitro effect of some Egyptian herbal extracts against Blastocystis hominis. J. Egypt. Soc. Parasitol. 2015, 45, 93–100. [Google Scholar] [CrossRef]
  132. Yakoob, J.; Abbas, Z.; Beg, M.A.; Naz, S.; Awan, S.; Hamid, S.; Jafri, W. In vitro sensitivity of Blastocystis hominis to garlic, ginger, white cumin, and black pepper used in diet. Parasitol. Res. 2011, 109, 379–385. [Google Scholar] [CrossRef]
  133. Abdel-Hafeez, E.H.; Ahmad, A.K.; Kamal, A.M.; Abdellatif, M.Z.; Abdelgelil, N.H. In vivo antiprotozoan effects of garlic (Allium sativum) and ginger (Zingiber officinale) extracts on experimentally infected mice with Blastocystis spp. Parasitol. Res. 2015, 114, 3439–3444. [Google Scholar] [CrossRef] [PubMed]
  134. Basyoni, M.M.A.; Fouad, S.A.; Amer, M.F.; Amer, A.F.; Ismail, D.I. Atorvastatin: In-Vivo Synergy with Metronidazole as Anti-Blastocystis Therapy. Korean J. Parasitol. 2018, 56, 105–112. [Google Scholar] [CrossRef] [PubMed]
  135. Mirza, H.; Wu, Z.; Teo, J.D.; Tan, K.S. Statin pleiotropy prevents rho kinase-mediated intestinal epithelial barrier compromise induced by Blastocystis cysteine proteases. Cell Microbiol. 2012, 14, 1474–1484. [Google Scholar] [CrossRef] [PubMed]
  136. Mossallam, S.F.; El-Mansoury, S.A.T.; Tolba, M.M.; Kohla, A.A.; Khedr, S.I. In vitro susceptibility of human Blastocystis subtypes to simeprevir. Saudi J. Biol. Sci. 2021, 28, 2491–2501. [Google Scholar] [CrossRef]
  137. Muturi, E.; Hong, W.; Li, J.; Yang, W.; He, J.; Wei, H.; Yang, H. Effects of simeprevir on the replication of SARS-CoV-2 in vitro and in transgenic hACE2 mice. Int. J. Antimicrob. Agents 2022, 59, 106499. [Google Scholar] [CrossRef] [PubMed]
  138. Vitetta, L.; Hall, S.; Linnane, A.W. Live probiotic cultures and the gastrointestinal tract: Symbiotic preservation of tolerance whilst attenuating pathogenicity. Front. Cell Infect. Microbiol. 2014, 4, 143. [Google Scholar] [CrossRef]
  139. Vitetta, L.; Saltzman, E.T.; Nikov, T.; Ibrahim, I.; Hall, S. Modulating the Gut Micro-Environment in the Treatment of Intestinal Parasites. J. Clin. Med. 2016, 5, 102. [Google Scholar] [CrossRef]
  140. Dinleyici, E.C.; Eren, M.; Dogan, N.; Reyhanioglu, S.; Yargic, Z.A.; Vandenplas, Y. Clinical efficacy of Saccharomyces boulardii or metronidazole in symptomatic children with Blastocystis hominis infection. Parasitol. Res. 2011, 108, 541–545. [Google Scholar] [CrossRef]
  141. Angelici, M.C.; Nardis, C.; Scarpelli, R.; Ade, P. Blastocystis hominis transmission by non-potable water: A case report in Italy. New Microbiol. 2018, 41, 173–177. [Google Scholar]
  142. Méabed, E.M.H.; Abdelhafez, D.N.; Abdelaliem, Y.F. Saccharomyces boulardii inhibits the expression of pro-inflammatory cytokines and inducible nitric oxide synthase genes in the colonic mucosa of rats experimentally-infected with Blastocystis subtype-3 cysts. Parasitology 2019, 146, 1532–1540. [Google Scholar] [CrossRef] [PubMed]
  143. Lepczyńska, M.; Dzika, E. The influence of probiotic bacteria and human gut microorganisms causing opportunistic infections on Blastocystis ST3. Gut Pathog. 2019, 11, 6. [Google Scholar] [CrossRef] [PubMed]
  144. Vitetta, L.; Palacios, T.; Hall, S.; Coulson, S. Gastrointestinal Tract Commensal Bacteria and Probiotics: Influence on End-Organ Physiology. Prog. Drug Res. 2015, 70, 1–33. [Google Scholar] [CrossRef] [PubMed]
  145. Perdigon, G.; Alvarez, S.; Rachid, M.; Agüero, G.; Gobbato, N. Immune system stimulation by probiotics. J. Dairy Sci. 1995, 78, 1597–1606. [Google Scholar] [CrossRef]
  146. Pais, P.; Almeida, V.; Yılmaz, M.; Teixeira, M.C. Saccharomyces boulardii: What Makes It Tick as Successful Probiotic? J. Fungi 2020, 6, 78. [Google Scholar] [CrossRef]
  147. Drider, D.; Bendali, F.; Naghmouchi, K.; Chikindas, M.L. Bacteriocins: Not Only Antibacterial Agents. Probiotics Antimicrob. Proteins 2016, 8, 177–182. [Google Scholar] [CrossRef]
  148. Bajaj, B.K.; Claes, I.J.J.; Lebeer, S. Functional mechanisms of probiotics. J. Microbiol. Biotechnol. Food Sci. 2015, 4, 321–327. [Google Scholar] [CrossRef]
  149. Cleusix, V.; Lacroix, C.; Vollenweider, S.; Le Blay, G. Glycerol induces reuterin production and decreases Escherichia coli population in an in vitro model of colonic fermentation with immobilized human feces. FEMS Microbiol. Ecol. 2008, 63, 56–64. [Google Scholar] [CrossRef]
  150. Oelschlaeger, T.A. Mechanisms of probiotic actions—A review. Int. J. Med. Microbiol. 2010, 300, 57–62. [Google Scholar] [CrossRef]
  151. Schneider, S.M.; Girard-Pipau, F.; Filippi, J.; Hebuterne, X.; Moyse, D.; Hinojosa, G.C.; Pompei, A.; Rampal, P. Effects of Saccharomyces boulardii on fecal short-chain fatty acids and microflora in patients on long-term total enteral nutrition. World J. Gastroenterol. 2005, 11, 6165–6169. [Google Scholar] [CrossRef]
  152. Nikolaki, M.D.; Kasti, A.N.; Katsas, K.; Petsis, K.; Lambrinou, S.; Patsalidou, V.; Stamatopoulou, S.; Karlatira, K.; Kapolos, J.; Papadimitriou, K.; et al. The Low-FODMAP Diet, IBS, and BCFAs: Exploring the Positive, Negative, and Less Desirable Aspects-A Literature Review. Microorganisms 2023, 11, 2387. [Google Scholar] [CrossRef] [PubMed]
  153. Yadav, M.K.; Kumari, I.; Singh, B.; Sharma, K.K.; Tiwari, S.K. Probiotics, prebiotics and synbiotics: Safe options for next-generation therapeutics. Appl. Microbiol. Biotechnol. 2022, 106, 505–521. [Google Scholar] [CrossRef] [PubMed]
  154. Kim, S.K.; Guevarra, R.B.; Kim, Y.T.; Kwon, J.; Kim, H.; Cho, J.H.; Kim, H.B.; Lee, J.H. Role of Probiotics in Human Gut Microbiome-Associated Diseases. J. Microbiol. Biotechnol. 2019, 29, 1335–1340. [Google Scholar] [CrossRef] [PubMed]
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Figure 1. Possible mechanisms of Blastocystis spp.-mediated colorectal cancer (own elaboration) (ROS, reactive oxygen species; NF-κB, nuclear factor kappa B; NOS, nitric oxide synthase; NO, nitric oxide; IL-8, interleukin-8; IL-6, interleukin-6; TNF-α, tumor necrosis factor alpha; TJs, tight junctions; ZO-1, zonula occludens-1 protein.
Figure 1. Possible mechanisms of Blastocystis spp.-mediated colorectal cancer (own elaboration) (ROS, reactive oxygen species; NF-κB, nuclear factor kappa B; NOS, nitric oxide synthase; NO, nitric oxide; IL-8, interleukin-8; IL-6, interleukin-6; TNF-α, tumor necrosis factor alpha; TJs, tight junctions; ZO-1, zonula occludens-1 protein.
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Figure 2. Mechanism of metronidazole action (own elaboration).
Figure 2. Mechanism of metronidazole action (own elaboration).
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MDPI and ACS Style

Pawelec-Pęciak, O.; Łanocha-Arendarczyk, N.; Grzeszczak, K.; Kosik-Bogacka, D. The Role of Blastocystis spp. in the Etiology of Gastrointestinal and Autoimmune Diseases. Pathogens 2025, 14, 313. https://doi.org/10.3390/pathogens14040313

AMA Style

Pawelec-Pęciak O, Łanocha-Arendarczyk N, Grzeszczak K, Kosik-Bogacka D. The Role of Blastocystis spp. in the Etiology of Gastrointestinal and Autoimmune Diseases. Pathogens. 2025; 14(4):313. https://doi.org/10.3390/pathogens14040313

Chicago/Turabian Style

Pawelec-Pęciak, Oliwia, Natalia Łanocha-Arendarczyk, Konrad Grzeszczak, and Danuta Kosik-Bogacka. 2025. "The Role of Blastocystis spp. in the Etiology of Gastrointestinal and Autoimmune Diseases" Pathogens 14, no. 4: 313. https://doi.org/10.3390/pathogens14040313

APA Style

Pawelec-Pęciak, O., Łanocha-Arendarczyk, N., Grzeszczak, K., & Kosik-Bogacka, D. (2025). The Role of Blastocystis spp. in the Etiology of Gastrointestinal and Autoimmune Diseases. Pathogens, 14(4), 313. https://doi.org/10.3390/pathogens14040313

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