Candida Overgrowth

The Hypothesis suggests that an imbalance in the intestinal microbiota, marked by an excessive proliferation of Candida species, can play a critical role in a range of diseases (Wu et al. 2021; Zhang et al. 2022). The mycobiota is only a small subset of the microbiota (Li et al. 2018), which has for long been neglected (Poulain et al. 2009; Enaud et al. 2018; Iyer and Ojcius 2024). But recent research has shed light on its major impact (d'Enfert 2009; d'Enfert et al. 2021).

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Dysbiosis

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A dysbiosis occurs when the ecosystem of bacteria, fungi, and other microorganisms is altered. Research on the microbiota-host relationship highlights its crucial role in maintaining health and how its dysregulation contributes to chronic diseases (Doré et al. 2017). Dysbiosis, characterized by a disrupted microbiota, is often accompanied by increased intestinal permeability, inflammation, and oxidative stress, representing a complex interplay involving intestinal barrier integrity and mucosal immunity (Lozupone et al. 2012; Sokol et al. 2008). Within this framework, fungi such as Candida may contribute to microbial imbalance and inflammatory responses, potentially playing a role in the chronic disease process (Hoarau et al. 2016; Mukherjee et al. 2015). The concept of dysbiosis as a disruption of homeostasis, marked by microbial imbalance and inflammatory responses, supports the idea that microbial diversity and stability are crucial for health. Studies by van de Guchte et al. further elucidate the importance of microbiota composition in influencing host metabolic pathways and the immune system, highlighting how specific microbial species can affect health outcomes (van de Guchte, Blottière, and Doré 2018).

 

Fungal dysbiosis is often characterized by an overgrowth of Candida species (Zhang et al. 2022). Candida albicans can induce inflammatory responses through several pathways. It elevates levels of intestinal permeability by disrupting tight junctions in the epithelial barrier (Moyes et al. 2016). The toxin Candidalysin plays a critical role in this process (Ho et al. 2021). This phenomenon, often described as "leaky gut" (Christovich and Luo 2022), allows endotoxins and other microbial byproducts to enter the bloodstream, contributing to systemic inflammation and immune activation. This translocation leads to a heightened immune response, involving pro-inflammatory cytokines such as IL-17, which can further perpetuate intestinal and systemic inflammation.

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Inflammatory Bowel Diseases

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Candida albicans may play a significant role in the pathogenesis of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Elevated levels of C. albicans have been linked to increased inflammation and disease severity in IBD patients. Studies show that fungal dysbiosis, particularly an overabundance of Candida spp., can exacerbate colitis and alter immune responses, contributing to disease progression (Gerard et al. 2015; Mukherjee et al. 2015; Kreulen et al. 2023). Animal models reveal that C. albicans colonization enhances colonic inflammation, suggesting a vicious cycle of inflammation and fungal overgrowth (Jawhara et al. 2008). Moreover, clinical data indicate that managing fungal populations might be crucial for IBD therapy (Hsia et al. 2023; Jangi et al. 2024).

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Primary sclerosing cholangitis

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Primary sclerosing cholangitis (PSC) is a chronic liver disease with unclear pathogenesis, often linked to inflammatory bowel diseases. PSC patients exhibit significant gut mycobiome alterations, with increased Candida species and other fungi, suggesting a complex interplay between bacterial and fungal dysbiosis in PSC progression (Rühlemann et al. 2020).

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Multiple Sclerosis

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Candida infections may be implicated in the development and severity of multiple sclerosis (MS). Systemic infections by Candida species have been shown to exacerbate experimental autoimmune encephalomyelitis (EAE), a model for MS, by increasing inflammatory responses and disease severity (T. F. C. Fraga-Silva et al. 2015; T. F. de C. Fraga-Silva et al. 2022). Some MS patients also exhibit higher levels of Candida species in the gut and oral cavity, with increased antibody titers against these fungi (Pisa, Alonso, and Carrasco 2011; da Cunha et al. 2020). These findings suggest a potential link between Candida infections and MS progression, warranting further investigation (Saroukolaei et al. 2016; Yadav et al. 2022).

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Celiac Disease

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Research indicates a potential link between Candida albicans and celiac disease (CeD). Candida albicans induces the production of anti-Saccharomyces cerevisiae antibodies (ASCA), markers for CeD and other autoimmune diseases (Sendid et al. 2024). Antibodies targeting Candida albicans' Hwp1 protein, similar to the gluten protein gliadin, are prevalent in CeD patients. This molecular mimicry suggests Candida infections may trigger CeD in genetically predisposed individuals (Corouge et al. 2015).

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Chronic Syndromes

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Candida albicans may play a role in the etiology of unexplained chronic syndromes such as chronic fatigue syndrome (Cater 1995), the irritable bowel syndrome (Santelmann and Howard 2005), and fibromyalgia (Berstad et al. 2020).

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Potential Implications for Treatment

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Addressing fungal dysbiosis may involve both dietary and pharmaceutical approaches. Dietary modifications, including the reduction of sugar and refined carbohydrates, can help limit the substrates available for Candida overgrowth (Otašević et al. 2018). Additionally, antifungal treatments, such as nystatin, could be effective in reducing fungal load in the gut, especially when combined with dietary interventions (Santelmann et al. 2001). Probiotics may also play a role in restoring balance to the gut microbiota, by promoting colonization resistance against fungal pathogens (Ricci et al. 2022).

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