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Review

Post-COVID Gut Dysbiosis and Its Role in Persistent Skin Disorders: A Gut–Skin Axis Perspective

by
Dorra Guermazi
1,* and
Elias Guermazi
2
1
Department of Dermatology, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA
2
Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA
*
Author to whom correspondence should be addressed.
COVID 2025, 5(4), 48; https://doi.org/10.3390/covid5040048
Submission received: 13 March 2025 / Revised: 25 March 2025 / Accepted: 27 March 2025 / Published: 31 March 2025
(This article belongs to the Section Long COVID and Post-Acute Sequelae)
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Abstract

:
The COVID-19 pandemic has led to persistent complications beyond the respiratory system, with emerging evidence highlighting the role of gut dysbiosis in long COVID. Given the established gut–skin axis, alterations in gut microbiota post-COVID-19 may contribute to persistent dermatologic conditions such as eczema, acne, and rosacea. This review explores the mechanisms by which SARS-CoV-2 disrupts the gut microbiome, leading to systemic inflammation and skin disease. Furthermore, it examines potential interventions, including probiotics, prebiotics, and dietary modifications, as microbiome-targeted therapeutic strategies for post-COVID dermatologic recovery. Understanding this link may open new avenues for treating chronic inflammatory skin conditions in long COVID patients.

1. Introduction

The COVID-19 pandemic has resulted in long-term sequelae beyond acute infection. This phenomenon is often termed “long COVID”, which encompasses persistent symptoms affecting multiple organ systems, including the gastrointestinal (GI) tract and skin [1]. Increasing evidence suggests that SARS-CoV-2 disrupts gut microbiota composition, leading to gut dysbiosis, which is characterized by not only an increase in pathogenic microbes but also a loss of beneficial bacteria [2,3].
The gut–skin axis is a well-established concept in dermatology: it acts as a modulator for understanding the relationship between the gut microbiome and inflammatory skin diseases. Given that COVID-19-induced gut dysbiosis is linked to systemic inflammation, these changes may be associated with persistent—or even worsening—dermatologic conditions such as eczema, acne, and rosacea in long COVID patients.
This review aims to explore the mechanisms by which SARS-CoV-2-induced gut dysbiosis may contribute to persistent skin disorders, examine the clinical implications of the gut–skin axis in long COVID, and evaluate potential microbiome-targeted interventions for managing post-COVID dermatologic conditions.

2. COVID-19 and Gut Dysbiosis

COVID-19 affects the GI tract through multiple mechanisms and leads to significant alterations in gut microbiota composition, a condition known as “gut dysbiosis” (the imbalance in the microbial community). This is not to be confused with the gut microbiome, which refers to the collective genetic material of these microorganisms and plays a crucial role in maintaining gut health. This disruption arises from direct viral invasion, immune activation, and COVID-19-related treatments, all of which contribute to persistent gastrointestinal and systemic inflammation. Emerging evidence suggests that these microbial imbalances may play a key role in the long-term sequelae of COVID-19, including dermatologic manifestations.

2.1. Direct Effects of SARS-CoV-2 on the Gut Microbiome

SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) receptors, which are highly expressed in intestinal epithelial cells [3,4]. This interaction enables the virus to invade the gut lining, causing cell damage, impaired nutrient absorption, and local inflammation [3,4]. Studies have shown that this process alters the gut microbiota by reducing beneficial bacterial species such as Bifidobacterium and Faecalibacterium prausnitzii, which are essential for maintaining immune balance and intestinal barrier integrity [4,5]. Simultaneously, the loss of these protective bacteria allows the overgrowth of pathogenic microbes like Enterococcus faecalis and Escherichia coli, which further contribute to gut inflammation and increased intestinal permeability [4,5].
In addition to bacterial imbalances, SARS-CoV-2 may also impact the gut virome, which is a collection of viruses that naturally live in the intestine. Viral infections can shift the composition of the virome and potentially influence microbial interactions and immune responses. While research on the gut virome in cases of “long COVID” is still emerging, preliminary findings suggest that viral-induced disruptions could contribute to prolonged dysbiosis and immune dysregulation [6,7].

2.2. Immune Activation and Persistent Inflammation

Beyond direct viral invasion, COVID-19 triggers systemic immune dysregulation, which plays a significant role in gut dysfunction. The infection leads to a surge in pro-inflammatory cytokines, particularly interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which disrupt gut homeostasis and contribute to chronic low-grade inflammation [8,9]. The presence of these microbial byproducts in circulation can trigger widespread systemic inflammation, which has been implicated in the exacerbation of inflammatory skin conditions.
Additionally, the gut–lung axis—which is a bidirectional relationship between gut microbiota and respiratory health—may further complicate post-COVIDsymptoms. Evidence from both human and animal studies suggests that gut dysbiosis can worsen pulmonary inflammation and vice versa, creating a cycle of persistent immune activation that prolongs recovery. In humans, long COVID patients with gut dysbiosis show increased systemic inflammation, particularly in the lungs and gastrointestinal tract. Animal studies further support this by demonstrating that gut dysbiosis leads to immune dysregulation, affecting immune cells like Th17 cells and macrophages, which contribute to inflammation in both the gut and lungs. This interplay may explain why many patients who have had long COVID experience both respiratory and GI symptoms, along with dermatologic issues linked to systemic inflammation [3,10].

2.3. The Role of COVID-19 Treatments in Gut Dysbiosis

Moreover, several treatments commonly used for COVID-19 may exacerbate gut microbiome imbalances. For example, broad-spectrum antibiotics are frequently administered to prevent secondary bacterial infections in hospitalized COVID-19 patients and can lead to significant microbial depletion. This is because they reduce bacterial diversity and thus increase one’s susceptibility to opportunistic pathogens [11]. The use of corticosteroids, which help control hyperinflammatory responses in severe COVID-19 cases, has also been associated with alterations in gut microbiota composition, including an increased risk of fungal overgrowth, particularly with Candida species [12].
Additionally, antiviral medications (such as Paxlovid) have been critical in reducing COVID-19 severity, but their impact on the gut microbiome is still under investigation. Some studies suggest that antiviral treatments may alter bacterial metabolism or disrupt microbial diversity, although the long-term consequences of these changes are not yet fully understood [13]. Understanding the role of COVID-19 therapies in shaping the gut microbiome is essential, as interventions aimed at restoring microbial balance may help mitigate some of the persistent symptoms seen in long COVID.

2.4. Clinical Evidence of Gut Dysbiosis in COVID-19 Survivors

Multiple studies have demonstrated that COVID-19 survivors experience persistent alterations in their gut microbiome, even months after recovering from the acute infection [10,14]. Stool analyses have revealed a significant reduction in beneficial bacteria and an increase in markers of intestinal permeability, indicating a compromised gut barrier [10,14]. Many individuals with long COVID report prolonged GI symptoms, such as bloating, diarrhea, constipation, and food sensitivities, which resemble patterns observed in irritable bowel syndrome (IBS) [10,15].
Interestingly, a subset of long COVID patients has also reported worsening skin conditions along with GI symptoms, which reinforces the relevance of the gut–skin axis [1] (more on this in Section 3). This connection suggests that systemic inflammation associated with gut dysbiosis may play a role in dermatologic manifestations such as eczema, acne, and psoriasis. Emerging evidence supports this link, with studies showing that gut dysbiosis in long COVID patients is associated with elevated levels of circulating inflammatory markers, such as IL-6 and TNF-α, which are known to exacerbate skin conditions [8,16]. As research into post-COVID gut health continues, identifying strategies to restore microbial balance is important in managing both GI and skin-related complications in long COVID patients.

3. The Gut–Skin Axis and Post-COVID Dermatologic Manifestations

The gut–skin axis is a well-recognized concept in dermatology, describing the bidirectional communication between the gut microbiome and skin health. This connection is primarily mediated through immune regulation, microbial metabolites, and intestinal permeability. In the context of COVID-19, viral-induced gut dysbiosis may contribute to systemic inflammation and immune dysfunction, exacerbating dermatologic conditions [17]. Many long COVID patients have reported persistent or new-onset skin issues, which may be linked to underlying gut microbial imbalances [18]. This section will explore this topic in more detail.

3.1. Mechanisms Linking Gut Dysbiosis to Skin Inflammation

The gut microbiome plays a crucial role in regulating systemic immune responses, and disruptions in microbial balance have been linked to chronic inflammation that may affect various organs, including the skin. One of the primary mechanisms driving this connection is the production of inflammatory cytokines in response to gut dysbiosis. When beneficial bacteria such as Bifidobacterium and Faecalibacterium prausnitzii are depleted, the gut environment shifts toward a more pro-inflammatory state [19]. This imbalance leads to increased levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and other cytokines that promote skin inflammation and worsen conditions such as eczema, acne, and psoriasis.
In addition to cytokine production, the disruption of the intestinal barrier allows bacterial endotoxins such as lipopolysaccharides (LPS) to enter the bloodstream. LPS activates toll-like receptor 4 (TLR4) on immune cells, including macrophages and dendritic cells, leading to the release of additional pro-inflammatory cytokines such as IL-1β and IL-17 [20]. These cytokines can migrate to the skin, where they promote inflammation by activating keratinocytes and recruiting T cells, particularly Th17 and Th22 cells, which are known to play a role in inflammatory skin diseases like psoriasis and eczema [21]. Animal models have shown that increased intestinal permeability results in elevated levels of circulating LPS, which correlates with exacerbated skin inflammation and impaired epidermal barrier function [22]. In human studies, patients with inflammatory skin conditions such as atopic dermatitis and psoriasis have been found to have higher levels of circulating LPS and Th17-related cytokines, suggesting a direct link between gut dysbiosis and skin inflammation [23].
Another important factor is the role of regulatory T cells (Tregs) in maintaining immune tolerance [24]. In a healthy gut, Tregs help suppress excessive immune responses and maintain barrier integrity. However, in the context of gut dysbiosis, Treg function is impaired, leading to unchecked inflammation. Studies in mice have demonstrated that the depletion of Tregs exacerbates skin inflammation, while the restoration of Treg function can mitigate these effects [25,26]. In humans, reduced Treg activity has been observed in patients with chronic inflammatory skin conditions, further supporting the role of immune dysregulation in the gut–skin axis [17,27].
Additionally, the gut microbiome influences sebum production and hormonal balance, both of which play key roles in acne and other inflammatory skin disorders [28]. Certain gut bacteria regulate androgen metabolism, and an imbalance in these microbes may contribute to increased sebum production and clogged pores, leading to acne flares. Dysbiosis also affects short-chain fatty acid (SCFA) production, particularly butyrate, which has anti-inflammatory properties and supports skin barrier function [29]. A reduction in SCFAs due to microbial imbalances may impair skin health, leading to increased dryness, irritation, and susceptibility to conditions like eczema [29].

3.2. Post-COVID Dermatologic Conditions Associated with Gut Dysbiosis

Many dermatologic conditions have been reported in long COVID patients, with emerging evidence suggesting a strong link to underlying gut dysbiosis [30,31]. One of the most common conditions observed is eczema (also known as atopic dermatitis), which is characterized by a heightened Th2-driven inflammatory response [22]. In post-COVID patients, gut microbial imbalances may promote Th2-skewed immunity which can exacerbate eczema symptoms. Studies have shown that individuals with atopic dermatitis often have lower levels of beneficial gut bacteria and increased intestinal permeability, both of which can be worsened by COVID-19-induced dysbiosis [22].
Acne and rosacea have also been reported in long COVID patients [16,32]. Some evidence suggests that gut dysbiosis may be linked to acne by increasing systemic inflammation and altering hormonal regulation [33]. Changes in gut bacteria may influence insulin sensitivity and androgen levels, leading to increased sebum production and a higher likelihood of acne breakouts. Similarly, rosacea—a chronic inflammatory skin disorder—has been associated with small intestinal bacterial overgrowth (SIBO), a condition linked to gut dysbiosis [33]. Post-COVID disruptions in gut microbiota may predispose individuals to SIBO, potentially worsening rosacea symptoms.
Another dermatologic condition linked to post-COVID gut dysbiosis is psoriasis, which is an autoimmune disorder characterized by the hyperproliferation of skin cells and chronic inflammation [34]. Recent research has highlighted the role of the gut microbiome in modulating immune responses in psoriasis patients [35,36]. Studies have found that individuals with psoriasis often have reduced levels of Akkermansia muciniphila, a beneficial gut bacterium involved in maintaining gut barrier integrity [37]. Post-COVID dysbiosis may further impair gut barrier function, increasing systemic inflammation and triggering psoriasis flares.
Beyond these conditions, some long COVID patients have reported new onset urticaria (hives), alopecia (hair loss), and vitiligo, suggesting broader immune dysregulation influenced by gut health [38]. While more research is needed to establish definitive links, these findings emphasize the potential role of gut dysbiosis in post-COVID dermatologic manifestations.

3.3. Clinical Evidence Supporting the Gut–Skin Axis in Long COVID

Several studies have reinforced the connection between gut dysbiosis and skin disorders in long COVID patients [39,40]. Clinical analyses of COVID-19 survivors have consistently shown altered gut microbiome profiles, with reduced bacterial diversity and increased inflammatory markers [41,42]. Many of these individuals experience prolonged GI symptoms, which often correlate with worsening skin conditions.
One study analyzing stool samples from long COVID patients found significantly lower levels of Bifidobacterium and Lactobacillus species, which are known to play protective roles in both gut and skin health [5]. The same study reported increased gut permeability markers, suggesting a direct link between microbial imbalances and systemic inflammation [5].
Moreover, research on pre-existing gut–skin interactions supports the hypothesis that COVID-19-induced dysbiosis may exacerbate dermatologic conditions. Previous studies have demonstrated that individuals with psoriasis, eczema, and acne tend to have distinct gut microbiome signatures, with reduced beneficial bacterial species and increased inflammatory markers. Given that COVID-19 disrupts similar microbial pathways, it is plausible that post-COVID gut disturbances play a significant role in skin health.
However, not all studies support a strong gut–skin connection in long COVID. Some research has found that while gut dysbiosis is common in long COVID patients, the correlation with skin conditions is less clear. One 2024 study found no significant association between gut microbiome alterations and the severity of skin conditions in long COVID patients, suggesting that other factors, such as direct viral effects or immune dysregulation, may play a more prominent role in dermatologic manifestations [10,43]. Similarly, a meta-analysis concluded that while gut dysbiosis is prevalent in long COVID, its impact on skin health may be overstated, with only weak correlations observed between gut microbiome changes and specific skin conditions like eczema and psoriasis [20,44].
Moreover, it is important to consider alternative explanations for post-COVID skin manifestations beyond gut microbiome changes. Systemic inflammation, driven by the persistent immune activation seen in long COVID, is a key factor that can directly impact skin health. Elevated levels of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-17 have been observed in long COVID patients, and these cytokines are known to exacerbate inflammatory skin conditions like eczema, psoriasis, and acne [8,18]. Endothelial dysfunction may further contribute to these dermatologic manifestations, as SARS-CoV-2 has been shown to directly infect endothelial cells, leading to vascular damage, impaired microcirculation, and increased vascular permeability [45,46]. These effects can manifest in the skin as rashes, chilblains, and livedo reticularis, which have been frequently reported in long COVID patients [47]. Endothelial injury also promotes a pro-thrombotic state, potentially contributing to vasculopathy-related skin conditions such as purpura and necrosis [48].
Additionally, autoimmune dysregulation triggered by SARS-CoV-2 infection may contribute to skin manifestations. For example, molecular mimicry between viral proteins and self-antigens can lead to the production of autoantibodies, which may target skin tissues and result in conditions such as urticaria, vitiligo, or alopecia areata [38]. Furthermore, endothelial dysfunction exacerbates systemic inflammation by increasing the release of pro-inflammatory cytokines and reactive oxygen species, creating a cycle of immune activation that worsens skin conditions [49]. A recent study found that long COVID patients with persistent skin symptoms exhibited elevated markers of endothelial activation, including von Willebrand factor and soluble thrombomodulin, highlighting the potential role of vascular pathology in post-COVID dermatologic changes [50].
Similarly, direct viral effects on the skin cannot be ruled out. SARS-CoV-2 has been shown to infect endothelial cells and disrupt vascular function, which may contribute to skin manifestations such as rashes, chilblains, and livedo reticularis [39]. These vascular changes, combined with systemic inflammation and immune dysregulation, provide alternative pathways for post-COVID skin conditions that are independent of gut microbiome alterations. These vascular changes, combined with systemic inflammation and immune dysregulation, provide additional mechanisms linking endothelial dysfunction to post-COVID skin conditions.

3.4. Implications for Treatment and Management

The role of the gut–skin axis in long COVID means there is the potential for microbiome-targeted interventions in managing post-COVID dermatologic conditions. Given that gut dysbiosis is a modifiable factor, restoring microbial balance could alleviate both GI and skin symptoms.
Dietary modifications—such as adopting an anti-inflammatory diet rich in fiber, polyphenols, and fermented foods—may support gut microbiome diversity and reduce systemic inflammation [51]. Probiotics, particularly strains from the Lactobacillus and Bifidobacterium genera, have shown promise in improving both gut and skin health. Prebiotics, which serve as nutrients for beneficial bacteria, may further enhance microbiome restoration [52]. Additionally, emerging therapies such as postbiotics (bacterial metabolites) and fecal microbiota transplantation (FMT) are being explored as potential interventions for severe gut dysbiosis [53].
Ultimately, addressing post-COVID gut dysbiosis may offer a novel approach to managing persistent skin conditions in long COVID patients, some of which are outlined in Table 1. Further research is needed to determine optimal treatment strategies, but current findings suggest that interventions targeting the gut microbiome could play a crucial role in dermatologic recovery.

4. Potential Microbiome-Targeted Interventions for Post-COVID Skin Health

Given the emerging evidence linking gut dysbiosis to dermatologic manifestations in long COVID, microbiome-targeted interventions represent a promising avenue for therapeutic development (Table 1 and Table 2). These interventions aim to restore the balance of the gut microbiota and reduce systemic inflammation with the goal of improving skin health. Several approaches, including dietary modifications, probiotics, prebiotics, and emerging therapies like fecal microbiota transplantation (FMT), are being explored as potential treatments for post-COVID skin complications [51,53]. This section delves deeper into the mechanisms, evidence, and potential benefits of these interventions.

4.1. Dietary Modifications and the Role of Anti-Inflammatory Diets

Diet plays a pivotal role in shaping the gut microbiome, and dietary modifications can be an effective strategy for promoting gut health and alleviating dermatologic symptoms in long COVID patients. An anti-inflammatory diet, rich in fiber, polyphenols, and fermented foods, can help restore gut microbiome balance by supporting the growth of beneficial bacteria as well as reducing inflammation [51].
The Mediterranean diet, for example, is known for its anti-inflammatory properties and has been shown to promote microbial diversity in the gut. This diet emphasizes the consumption of fruits, vegetables, whole grains, healthy fats (e.g., olive oil), and lean proteins, all of which provide nutrients that support gut health [60]. The Mediterranean diet is also rich in polyphenols—plant compounds found in foods like berries, nuts, and olive oil—that have antioxidant properties and help reduce systemic inflammation. In a study focusing on the Mediterranean diet’s effects on the gut microbiome, participants exhibited higher levels of beneficial bacteria, including Bifidobacterium and Lactobacillus, which are associated with improved immune function and gut barrier integrity [61].
Additionally, fiber-rich foods such as whole grains, legumes, and vegetables are essential for maintaining gut health. Fiber serves as a prebiotic, providing nourishment for beneficial gut bacteria. The fermentation of fiber by gut microbes produces short-chain fatty acids (SCFAs), particularly butyrate, which have anti-inflammatory properties and help maintain the integrity of the intestinal barrier [62]. Increased SCFA production may also have direct benefits for skin health, as these metabolites help reduce systemic inflammation that could otherwise exacerbate skin conditions such as eczema, acne, and psoriasis [63].
Conversely, it is important to avoid diets high in processed foods, refined sugars, and high-glycemic-index carbohydrates, as these can promote the growth of pathogenic bacteria and increase gut inflammation. Evidence suggests that such diets contribute to microbial imbalances that can worsen both gastrointestinal and dermatologic symptoms [17]. Thus, dietary changes aimed at reducing inflammation and promoting microbial diversity may offer significant benefits for long COVID patients.

4.2. Probiotics and Prebiotics for Restoring Gut Balance

Probiotics and prebiotics are two microbiome-targeted interventions that have shown promise in restoring gut balance and alleviating post-COVID skin conditions. Probiotics are live microorganisms that, when administered in adequate amounts, confer health benefits to the host. Specific strains of probiotics have been shown to modulate immune responses, reduce inflammation, and improve gut barrier function, all of which may help alleviate skin conditions associated with gut dysbiosis [64].
Among the most studied probiotic strains for gut–skin health are Lactobacillus and Bifidobacterium species. Research has demonstrated that these probiotics can help reduce inflammation in individuals with conditions like eczema, acne, and rosacea [64]. For example, a study involving patients with eczema found that supplementation with Lactobacillus rhamnosus GG led to a reduction in skin inflammation and improvement in symptoms [65]. Similarly, Bifidobacterium strains have been shown to promote gut health and reduce systemic inflammation, which could benefit skin conditions driven by immune dysregulation [66].
Prebiotics, on the other hand, are non-digestible food components (often fibers) that selectively stimulate the growth or activity of beneficial gut bacteria. Prebiotics serve as fuel for probiotic bacteria and can promote the growth of protective species that enhance gut health. Common prebiotics include inulin, resistant starch, and fructooligosaccharides (FOS), which have been shown to support the growth of beneficial bacteria such as Bifidobacterium and Lactobacillus. These beneficial bacteria, in turn, help maintain intestinal barrier function and regulate systemic immune responses. In clinical studies, prebiotic supplementation has been shown to improve gut microbiota composition and reduce markers of systemic inflammation, which may have downstream effects on skin health [17,67].
When used together, probiotics and prebiotics can have a synergistic effect, promoting the restoration of a balanced microbiome and reducing the chronic inflammation that often underlies dermatologic conditions in long COVID patients [68]. This combined approach may provide an effective strategy for managing post-COVID skin complications.

4.3. Fecal Microbiota Transplantation (FMT) and Emerging Therapies

Fecal microbiota transplantation (FMT) is an innovative therapy that involves transferring stool from a healthy donor into the gastrointestinal tract of a patient with gut dysbiosis. The goal of FMT is to restore microbial diversity and re-establish a healthy microbiome. While FMT has been primarily used to treat Clostridium difficile infections, there is growing interest in its potential for treating a wide range of diseases, including long COVID and associated dermatologic conditions [69].
Animal models have provided key insights into the mechanisms by which FMT restores gut homeostasis [70,71]. Studies in germ-free mice have shown that FMT can reduce systemic inflammation, improve gut barrier integrity, and modulate immune responses, leading to improved skin health in models of inflammatory skin diseases such as psoriasis and atopic dermatitis [17,72]. Additionally, FMT-treated animals exhibited increased levels of beneficial short-chain fatty acid (SCFA)-producing bacteria, suggesting a potential link between microbiota restoration and reduced skin inflammation [73].
In patients with severe gut dysbiosis, FMT has been shown to restore microbiome balance, increase microbial diversity, and improve gut barrier function [74]. Clinical trials have demonstrated its effectiveness in conditions like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), but data on dermatologic applications remain limited [75]. Small-scale human studies suggest that FMT may reduce systemic inflammation and improve symptoms in conditions such as psoriasis and atopic dermatitis [70].
Despite its potential, FMT has significant limitations. Variability in donor microbiota composition, a lack of standardized treatment protocols, and concerns about long-term safety present challenges for widespread clinical use [76]. Additionally, adverse effects such as transient gastrointestinal discomfort and, in rare cases, serious infections, highlight the need for rigorous screening and regulation [69]. Future research should focus on optimizing donor selection, treatment standardization, and long-term follow-up in clinical trials to determine the feasibility of FMT as a dermatologic therapy for long COVID.
In addition to FMT, emerging pharmacological therapies that target gut inflammation are also being explored as potential treatments for post-COVID skin health. For example, rifaximin—a non-absorbable antibiotic that targets the gut microbiome—has shown promise in treating conditions like irritable bowel syndrome (IBS) and could potentially benefit long COVID patients with GI symptoms [77]. Butyrate supplements, which are used to increase SCFA production and support gut barrier integrity, are also being investigated for their potential to reduce inflammation and improve skin health [62]. Preclinical studies suggest that butyrate supplementation enhances intestinal barrier function and decreases inflammatory cytokine production, but human trials specific to dermatologic conditions in long COVID are still needed.

4.4. The Role of Personalized Microbiome-Based Approaches

One of the key challenges in microbiome-based interventions is the variability in individual responses to treatment. Microbial composition is influenced by numerous factors, including genetics, diet, lifestyle, and pre-existing health conditions, meaning that there is no one-size-fits-all solution [78,79]. As such, personalized microbiome-based approaches offer a more effective means of managing post-COVID skin health.
Precision probiotics tailored to an individual’s specific microbiome profile may optimize the therapeutic effects of probiotics and prebiotics. Advances in microbiome sequencing technologies now allow for the identification of unique microbial signatures, which can inform the selection of targeted probiotics and prebiotics to restore gut balance [80]. In the future, microbiome testing may become a standard part of long COVID treatment protocols, helping to guide personalized interventions for both gut and skin health.
Similarly, dietary interventions could be customized based on an individual’s gut microbiome profile, ensuring that dietary changes are aligned with the specific needs of the patient’s microbiota.
By incorporating personalized nutrition, precision medicine, and microbiome-based therapies, it may be possible to develop highly effective, individualized treatment plans for long COVID patients suffering from dermatologic issues linked to gut dysbiosis (Table 2).
Table 2. Potential microbiome-targeted interventions for skin health.
Table 2. Potential microbiome-targeted interventions for skin health.
InterventionMechanismEvidence for Effectiveness
Probiotics (Lactobacillus, Bifidobacterium)Restores gut balance, reduces inflammation [81]Shown to improve acne, eczema, and rosacea symptoms
Prebiotics (inulin, resistant starch)Promotes beneficial bacterial growth [82]Supports microbiome restoration, reduces systemic inflammation
Fecal microbiota transplantation (FMT)Restores gut microbial diversity [83]Experimental but promising for treating gut dysbiosis and associated conditions
Anti-inflammatory diet (Mediterranean, fiber-rich)Reduces systemic inflammation, supports gut health [84]Shown to promote gut microbial diversity, improve immune function
Butyrate supplementationSupports gut barrier function, reduces gut inflammation [85]Enhances SCFA production, reduces inflammation, supports skin health

5. Discussion

The evidence supporting the link between COVID-19-induced gut dysbiosis and persistent dermatologic conditions in long COVID is compelling (Figure 1), but further exploration is needed [20,43].
The gut–skin axis presents an intriguing target for potential therapies, yet much remains unclear about the precise mechanisms at play. Increased intestinal permeability and the release of pro-inflammatory cytokines highlight the complexity of this relationship, with conditions such as eczema, acne, and psoriasis emerging as potential manifestations of this dysbiosis [8,9,86].
Therapeutically, the promise of microbiome-targeted interventions is evident, with approaches like probiotics, prebiotics, and dietary modifications showing potential for improving both gut and skin health. While dietary changes, such as adopting an anti-inflammatory Mediterranean diet, are beneficial, the role of FMT remains experimental, and its long-term effects are still uncertain. Likewise, while probiotics like Lactobacillus and Bifidobacterium demonstrate benefits, particularly in conditions like eczema and acne, the variability in patient responses underscores the need for personalized approaches [5].
Dermatologists can integrate microbiome-targeted interventions into clinical practice by evaluating patients’ gut health as part of a comprehensive approach to managing dermatologic conditions. This could involve recommending probiotic and prebiotic supplements, dietary adjustments, and, where appropriate, referrals for further microbiome-based therapies like FMT. As the evidence base grows, dermatologists may also incorporate microbiome sequencing to personalize treatments, targeting specific microbial imbalances contributing to skin conditions.
A key challenge is the inherent individual variability in microbiota composition, which complicates the application of one-size-fits-all interventions. Advances in microbiome sequencing will be critical for refining personalized treatment plans, allowing for more effective targeting of gut–skin interactions. For long COVID patients with persistent skin disorders, it may be beneficial to consider gut microbiome testing as part of a diagnostic workup, especially when traditional treatments fail. This could help identify underlying dysbiosis contributing to skin symptoms and guide targeted microbiome-based therapies.
Ultimately, integrating precision medicine into long COVID care will offer the best potential for addressing the complex interplay between the gut and skin, but more research is needed to establish clear guidelines and optimize therapeutic strategies.

Limitations and Future Research Directions

Despite the promising potential of microbiome-targeted therapies, several limitations remain. Much of the research on the gut–skin axis in long COVID is observational, with controlled clinical trials still lacking. Most studies rely on stool samples, but the complex relationship between gut microbiota and dermatologic outcomes is influenced by factors such as genetics, medication use, and pre-existing health conditions. Additionally, the roles of the gut virome and fungal microbiome in post-COVID dysbiosis remain unclear, and while bacterial imbalances have been the primary focus, viral and fungal dysbiosis may also contribute to inflammation and dermatologic symptoms.
A key limitation is the lack of large-scale, longitudinal studies tracking microbiome changes in long COVID, making it difficult to establish causative links to dermatologic outcomes. Furthermore, there are too few clinical trials assessing microbiome-targeted interventions for skin conditions, hindering the development of evidence-based treatment protocols. Long-term studies are essential to evaluate the durability and effectiveness of these interventions in managing long-term dermatologic symptoms in long COVID patients.
Future research should prioritize longitudinal studies to track microbiome changes over time and their relationship to dermatologic outcomes. Clinical trials assessing the efficacy of probiotics, prebiotics, dietary modifications, and FMT in treating both gastrointestinal and dermatologic symptoms are crucial. In particular, randomized controlled trials on probiotic treatments for post-COVID dermatologic conditions are needed to establish standardized therapeutic guidelines. Additionally, studies should explore personalized microbiome-based therapies using advances in metagenomics and metabolomics to tailor interventions. The ultimate goal is to develop integrated, multi-disciplinary treatment approaches that address the interconnected nature of gut, skin, and immune health in long COVID (Figure 1).

6. Conclusions

COVID-19-induced gut dysbiosis has emerged as a key factor in the persistence of gastrointestinal and dermatologic symptoms in long COVID. Disruptions in the gut microbiome have been associated with systemic inflammation, increased intestinal permeability, and immune dysregulation, which may influence skin conditions such as eczema, acne, rosacea, and psoriasis. Addressing these imbalances through microbiome-targeted therapies—such as dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation (FMT)—may offer a more effective, holistic approach to managing post-COVID complications.
Beyond long COVID, understanding the gut–skin axis has significant implications for other chronic diseases linked to gut dysbiosis. Conditions such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), psoriasis, and atopic dermatitis share common pathways of immune dysfunction and microbial imbalance. Research into COVID-19’s impact on the gut may provide valuable insights into these conditions, potentially leading to microbiome-based therapies that can improve both gut and skin health.
Additionally, studying the long-term effects of viral infections on the microbiome could reshape how we approach chronic conditions following illnesses like HIV, hepatitis C, and influenza. Understanding how viruses alter microbial ecosystems and contribute to prolonged inflammation may pave the way for novel therapeutic strategies, including precision probiotics, dietary interventions, and targeted microbiome restoration.
By further exploring the gut–skin axis in long COVID, researchers can develop more personalized and preventative approaches for managing post-viral syndromes and chronic inflammatory conditions, ultimately improving long-term patient outcomes. As it turns out, what happens in the gut does not stay in the gut—so maybe the best skincare routine starts with a spoon, not a serum.

Author Contributions

D.G.: Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Writing—original draft, Writing—review & editing. E.G.: Resources, Validation, Writing—review & editing. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflicts of interest.

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Covid 05 00048 g001
Figure 1. The gut–skin axis in long COVID. COVID-19 can disrupt gut microbiota, leading to gut dysbiosis, which causes increased intestinal permeability and systemic inflammation. This inflammatory response contributes to skin conditions such as eczema, acne, psoriasis, and rosacea, with persistent symptoms in long COVID. Potential interventions, including probiotics, an anti-inflammatory diet, fecal microbiota transplantation (FMT), and SCFA supplementation, may help restore gut balance and reduce skin-related symptoms.
Figure 1. The gut–skin axis in long COVID. COVID-19 can disrupt gut microbiota, leading to gut dysbiosis, which causes increased intestinal permeability and systemic inflammation. This inflammatory response contributes to skin conditions such as eczema, acne, psoriasis, and rosacea, with persistent symptoms in long COVID. Potential interventions, including probiotics, an anti-inflammatory diet, fecal microbiota transplantation (FMT), and SCFA supplementation, may help restore gut balance and reduce skin-related symptoms.
Covid 05 00048 g001
Table 1. Common dermatologic conditions linked to post-COVID gut dysbiosis.
Table 1. Common dermatologic conditions linked to post-COVID gut dysbiosis.
Skin ConditionProposed Mechanism via Gut–Skin AxisPotential Microbiome-Based Intervention
EczemaTh2-driven inflammation worsened by dysbiosis [54]Probiotics (Lactobacillus, Bifidobacterium), prebiotic fiber
AcneIncreased systemic inflammation, hormonal imbalance [55]Low-glycemic diet, gut-healing supplements
PsoriasisIncreased intestinal permeability [56]Anti-inflammatory diet, SCFA supplementation
RosaceaSmall intestinal bacterial overgrowth (SIBO) [57]Probiotics (e.g., Lactobacillus), dietary adjustments (e.g., low FODMAP)
Urticaria (hives)Immune dysregulation due to gut imbalance [58]Antihistamine therapy, probiotics
Alopecia (hair Loss)Immune system dysregulation, inflammation [59]Probiotics, anti-inflammatory diet
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Guermazi, D.; Guermazi, E. Post-COVID Gut Dysbiosis and Its Role in Persistent Skin Disorders: A Gut–Skin Axis Perspective. COVID 2025, 5, 48. https://doi.org/10.3390/covid5040048

AMA Style

Guermazi D, Guermazi E. Post-COVID Gut Dysbiosis and Its Role in Persistent Skin Disorders: A Gut–Skin Axis Perspective. COVID. 2025; 5(4):48. https://doi.org/10.3390/covid5040048

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Guermazi, Dorra, and Elias Guermazi. 2025. "Post-COVID Gut Dysbiosis and Its Role in Persistent Skin Disorders: A Gut–Skin Axis Perspective" COVID 5, no. 4: 48. https://doi.org/10.3390/covid5040048

APA Style

Guermazi, D., & Guermazi, E. (2025). Post-COVID Gut Dysbiosis and Its Role in Persistent Skin Disorders: A Gut–Skin Axis Perspective. COVID, 5(4), 48. https://doi.org/10.3390/covid5040048

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