The gut microbiome is a broad and dynamic ecosystem of microorganisms found in the gastrointestinal tract. It has been increasingly recognized for its role in systemic health and disease.¹ The microbial cells living in and on the human body are estimated to be as numerous as our own cells, highlighting their potential impact on physiological processes.² Next-generation sequencing (NGS) has enhanced our ability to study the human microbiome by identifying previously unculturable microorganisms and providing insights into their potential functions.³ These tests have been widely utilized in oncology, where NGS is employed to identify tumor-specific genetic mutations to provide patients with targeted therapies.^4,5

These successes have researchers now asking whether identifying microbes could also help guide more personalized treatments. Microbiome testing is used to identify dysbiosis linked to inflammatory skin conditions, bowel diseases, metabolic disorders, cardiovascular diseases, and neurodevelopmental conditions.^6,7 Building on these findings, microbiome-targeted interventions like dietary modifications, probiotics, prebiotics, and fecal microbiota transplantation are being explored to correct suspected dysbiosis and improve clinical outcomes.⁷ In parallel, researchers are using microbiome testing to develop nutrition models that provide dietary changes for specific microbiome profiles, with the goal of improving treatment outcomes for a range of conditions.⁸ The microbiome plays a role in skin barrier integrity and immune modulation, making these advancements of particular importance in the field of dermatology.

Despite growing enthusiasm, the clinical utility of microbiome sequencing in everyday practice remains uncertain. While research has demonstrated the microbiome’s broad influence on host traits, metabolism, and immunity, translating these associations into targeted therapies remains complex due to microbial variability, host genetics, and environmental factors.⁹ Another challenge is that microbiome-based interventions may not last, as gut communities often shift quickly and can return to their original state, or an altogether new and different dysbiotic state, after only short-term changes.¹⁰ (See Figure 1)

Figure 1.

Figure 1. The microbiome is complex and may be a moving target. A perturbation (such as antibiotics or an environmental stressor) could cause a dysbiotic state to occur. A resilient system may self-correct, or correction may occur as the result of an intervention. However, the intervention (or simply time with a lack of resilience) may result in a new, stable alternative state that is also dysbiotic. (After: Lange K, Buerger M, Stallmach A, Bruns T. Effects of antibiotics on gut microbiota. Digestive Diseases. 2016;34(3):260-8.)

This review evaluates microbiome testing tools, their clinical applications, emerging therapies, and the barriers that must be overcome to make microbiome-guided care actionable and evidence-based. It also examines host-directed strategies, microbiome-targeted therapies, and their potential role in advancing personalized medicine in fields influenced by the microbiome, like dermatology.

Integrating microbiome testing into clinical care requires a structured evaluation of available tools, their analytical strengths and limitations, and their relevance to patient management. This section outlines key testing modalities and the types of insights each provides. These include methods such as next-generation sequencing, metagenomic analysis, and microbial metabolite profiling, which can characterize microbial communities and infer their functional potential. These tools continue to expand our understanding of the human microbiome and its associations with disease.¹¹

Among the most commonly used microbiome testing methods is 16S rRNA sequencing, which identifies the types of bacteria present in a sample.¹² This technique works by detecting a specific generative marker shared by all bacteria, which allows estimates to be made about which types are present without needing to grow them in the lab.¹² Another commonly used method is shotgun metagenomics, which offers detailed information about microbial genomes present in a sample.¹² Unlike 16S sequencing, shotgun metagenomics randomly sequences all of the DNA in a sample, which can provide a more detailed view of all the microbes, including bacteria, viruses, and fungi.¹²

Metabolomic profiling detects microbial byproducts like short-chain fatty acids, offering functional insight beyond taxonomy.¹³ This profiling measures the small molecules produced during metabolism, helping researchers gain a better understanding of what role the microbiome is playing in inflammation, digestion, and immunity.¹³ Metatranscriptomics measures RNA transcripts to monitor which microbial genes are actively being expressed at a given moment, offering insights into microbial roles and metabolic activities.¹⁴ This method captures a real-time snapshot of what microbial genes are turned on or off, helping researchers gain an understanding of what microbes are actively doing instead of just indicating which ones are present in a sample.¹⁴ Culturomics takes a high-throughput, culture-based approach, systematically applying numerous culture conditions in parallel to grow and identify live microbes, including ones that other sequencing techniques may miss.¹⁵ This technology creates growth conditions that allow live bacteria to be recovered that were originally believed to be unculturable.¹⁵ As a result, culturomics has significantly expanded our understanding of microbial diversity.¹⁵

These methods have advanced the field, but each has distinct strengths and limitations. 16S rRNA sequencing offers a relatively affordable way to study bacterial communities and is useful for genus-level identification, but it struggles to distinguish closely related species and can be influenced by primer bias, the phenomenon where certain microbial species are preferentially amplified over others due to differences in primer binding efficiency.¹⁶ Shotgun metagenomics can identify microbes at the species level and detect rare or novel organisms, but its high cost and reliance on incomplete reference databases remain major limitations.^17,18 Metabolomic profiling sheds light on host-microbe interactions by detecting microbial byproducts, but interpretation is complicated by data complexity and the lack of standardization.¹⁹ Metatranscriptomics connects microbiome composition to function by measuring gene expression, though RNA degradation and host background noise remain significant hurdles.²⁰ Although culturomics have broadened our knowledge of microbial diversity by recovering previously unculturable bacteria, it is a more time-consuming process that is significantly more expensive than other techniques.²¹

Together, these methods have greatly expanded our understanding of the microbiome, but applying that knowledge in everyday clinical practice remains challenging. Ongoing issues with standardization and the absence of clear definitions of what constitutes a healthy microbiome still limit their ability to guide concrete, evidence-based care.^22,23

Gut microbiome testing has become an important tool for understanding how microbial communities influence human health, offering insights into various diseases. It first gained clinical relevance in gastrointestinal diseases, where it was used to assess microbial composition and guide interventions for conditions like Clostridioides difficile infections.²⁴ In such cases, therapeutic options are viable and evidence-based. Clostridioides difficile infections are effectively treated with oral vancomycin or fidaxomicin, both of which have demonstrated efficacy in randomized controlled trials.²⁵

Gut microbiome testing has also been integrated into dermatology, where research has demonstrated its role in conditions such as psoriasis, atopic dermatitis, acne vulgaris, rosacea, alopecia areata, and hidradenitis suppurativa.²⁶ Studies have shown that disruptions along the gut-skin axis can contribute to inflammation and immune dysregulation, influencing the severity and progression of these skin diseases.²⁶ In laboratory settings, microbiome testing is used to explore microbial imbalances that may contribute to disease severity. However, there are currently no validated microbial thresholds or treatment algorithms guiding dermatologic care.²⁶ In other organ systems, proposed thresholds of dysbiosis have generally been derived empirically from population-level comparisons between well-characterized disease cohorts and healthy controls, often within narrowly defined clinical contexts. Even in these settings, such thresholds are indication-specific, platform-dependent, and subject to ongoing revision as analytic methods and reference datasets evolve.

In atopic dermatitis and psoriasis, distinct microbial signatures correlate with disease severity. Similar imbalances have also been noted in acne, rosacea, and seborrheic dermatitis.^27,28 Unlike the well-defined microbial disruptions seen in Clostridioides difficile infections, patterns observed in dermatologic diseases are inconsistent, with no thresholds on what is considered dysbiotic, and few evidence-based treatments are available.

Gut microbiome testing has also been applied across various medical specialties, providing insights into disease mechanisms and helping inform patient management. In oncology, microbiome composition has been linked to responses to immunotherapy and chemotherapy, influencing treatment efficacy and side effect profiles.²⁹ In neurology and psychiatry, alterations in gut microbial diversity have been associated with conditions such as Parkinson’s disease, multiple sclerosis, and depression, supporting the concept of the gut-brain axis in neuroinflammatory and neurodegenerative disorders.³⁰ In metabolic and endocrine diseases, microbiome analysis has been used to study its role in obesity, type 2 diabetes, and metabolic syndrome, where gut bacteria influence insulin resistance and systemic inflammation.³¹ Additionally, in autoimmune and rheumatologic conditions such as rheumatoid arthritis and systemic lupus erythematous, microbiome testing has provided insights into dysbiosis-driven immune modulation.³² These applications underscore the expanding role of microbiome testing in modern medicine, offering valuable insights into disease pathophysiology and informing potential therapeutic strategies across multiple specialties.

Emerging evidence suggests that certain lifestyle factors can influence microbial composition, providing opportunities for targeted, non-pharmacologic interventions. By identifying patterns of dysbiosis, these tests provide personalized recommendations to optimize factors that influence gut microbial composition.

Diet plays a central role in shaping microbiome composition. High-fiber, plant-based diets have been associated with increased microbial diversity and production of short-chain fatty acids, which support gut and immune health.³³ In contrast, diets high in processed foods, artificial sweeteners, and excessive animal fats have been linked to dysbiosis and increased inflammation.³⁴ Dietary interventions targeting the microbiome have also emphasized the role of whole, minimally processed foods in promoting microbial stability and metabolic health. Fermented foods such as yogurt, kimchi, and sauerkraut contain live bacterial cultures that can support beneficial gut bacteria and enhance gut barrier integrity.³⁵ Additionally, polyphenol-rich foods found in berries, green tea, and dark chocolate have been shown to modulate microbial composition by selectively promoting beneficial bacteria while inhibiting opportunistic pathogens.³⁶ Reducing excessive consumption of refined sugars and emulsifiers linked to gut permeability and pro-inflammatory microbial shifts is another key strategy for maintaining microbial balance.³⁷

Beyond diet, other lifestyle factors play a role in shaping the microbiome. Physical activity has been linked to increased microbial diversity, with studies showing elevated levels of butyrate-producing taxa in athletes compared to sedentary individuals.^38,39 Sleep and circadian rhythms also influence gut microbial composition, with poor sleep quality and irregular sleep schedules associated with microbial imbalances.⁴⁰ Additionally, chronic stress has been shown to alter gut microbiota, contributing to systemic inflammation and metabolic changes.⁴¹

Many interventions seek to alter the microbiome to improve health outcomes. Some therapies aim to restore microbial balance by introducing beneficial bacteria, while others attempt to modify the gut environment to favor a healthier microbial composition. Some of these interventions are now marketed with personalized recommendations based on an individual’s microbiome profile.⁴² Although microbiome therapies are gaining popularity, strong clinical evidence to support their effectiveness remains limited.⁴³ As a result, it remains unclear whether personalizing these interventions based on microbiome data leads to meaningful health outcomes.

Probiotics are live microorganisms that can support health by influencing gut microbiota, strengthening the gut barrier, and regulating immune and metabolic functions.⁴⁴ (See Figure 2) These supplements are commonly marketed to improve gut health by restoring microbial balance, especially in cases of dysbiosis. Several studies have shown that probiotics can influence immune responses, enhance gut barrier function, and alter microbiome composition.⁴⁴ Studies have shown that Lactobacillus rhamnosus may reduce pediatric antibiotic-associated diarrhea, while Bifidobacterium infantis has shown benefit in irritable bowel syndrome in some.^45,46 However, the effects of probiotics are highly strain-specific and context-dependent, as different strains within the same species can produce markedly different outcomes.⁴⁴ While there is evidence supporting probiotic use in particular conditions and situations, the benefit of probiotics in broader populations or as a personalized microbiome intervention remains inconsistent.⁴⁷ Another major challenge is that many over-the-counter probiotics lack clinical validation or standardized formulas.⁴⁸

From a clinical perspective, probiotics have demonstrated benefit in select, well-defined settings, most notably in the prevention of antibiotic-associated diarrhea and in certain functional gastrointestinal disorders. Benefits are generally modest and condition-specific, with outcomes depending heavily on strain selection, formulation, dosing, and host factors. Importantly, observed effects cannot be generalized across probiotic products, as different strains may exert distinct or opposing biological effects.

Several challenges limit broader clinical translation of probiotics as therapeutic tools. Commercial formulations vary widely with respect to strain composition, concentration, viability (eg, live versus spore-forming organisms), manufacturing quality, and stability over time. In addition, many products lack rigorous clinical validation, and regulatory oversight remains inconsistent. As a result, while probiotics can offer benefit in specific contexts, predicting individual response or integrating probiotic use into personalized microbiome-guided care remains difficult. A comprehensive review of probiotic efficacy across conditions is beyond the scope of this article.

Figure 2.

Prebiotics are non-digestible food components that selectively stimulate the growth and activity of beneficial gut bacteria.⁴⁹ They serve as a fuel source for commensal microbes, promoting a healthier microbial composition and enhancing the production of short-chain fatty acids, which support gut and immune function.⁵⁰ Clinical studies have shown that prebiotics can increase microbial diversity and improve metabolic and inflammatory markers, though outcomes often vary depending on one’s individual microbiome composition and dietary context.⁵¹ While some trials report improvements in insulin sensitivity, inflammatory cytokines, and gut permeability, others have found limited or no clinical change despite shifts in microbiota.^52,53 These inconsistencies suggest that changes in microbial composition do not always lead to clinically meaningful therapeutic outcomes.⁴⁷ This variability in responsiveness may reflect differences in baseline microbiome composition, host genetics, and environmental exposures, underscoring the need for more personalized approaches.

In contrast to probiotics, which involve administration of live organisms, and prebiotics, which act indirectly by shaping the existing microbial ecosystem, evidence supporting postbiotics (non-viable microbial products or metabolites) remains limited and largely preliminary. Postbiotics have been proposed as a means of leveraging microbial benefits without the challenges of live organism delivery. They are thought to act through immune modulation, barrier support, and host–microbe signaling pathways, with theoretical advantages related to stability and safety. However, clinical evidence remains preliminary, and their therapeutic role has yet to be clearly defined.

Antibiotics can significantly alter the gut microbiome by reducing microbial diversity and shifting community composition.⁵⁴ While often used to treat infection, certain antibiotics have been repurposed to modulate the microbiome in non-infectious conditions.⁵⁵ Rifaximin is a non-absorbable antibiotic used in the management of IBS and hepatic encephalopathy to reduce symptom severity by selectively suppressing overrepresented microbial populations.⁵⁵ Despite studies showing the efficacy of using antibiotics to modulate the microbiome, their use as a microbiome-targeted therapy remains controversial. The use of antibiotics can disrupt microbial homeostasis, promote the overgrowth of opportunistic pathogens, and increase the risk of antibiotic resistance.⁵⁶ Another challenge that antibiotics pose is that their induced changes in the microbiome may be long-lasting, with studies showing that some microbiomes fail to fully recover months after treatment.⁵⁴ While antibiotics may offer some therapeutic benefit in select cases, their use as microbiome-modulating tools is limited by their lack of precision and potential to cause lasting disruption to microbial balance.^54,56

Fecal microbiota transplantation (FMT) involves the transfer of stool from a healthy donor to a recipient into the gastrointestinal tract of a recipient, with the aim of restoring microbial diversity and gut homeostasis.⁵⁷ It has been most successful in treating recurrent Clostridioides difficile infection, with multiple randomized controlled trials reporting cure rates over 85%.⁵⁷ FMT is also being explored as a treatment for other conditions associated with dysbiosis, including ulcerative colitis, IBS, hepatic encephalopathy, and certain inflammatory dermatologic conditions (eg, atopic dermatitis and hidradenitis suppurativa), as well as a small number of exploratory reports in autoimmune skin disease (eg, alopecia areata).^58–60 While early studies have shown some promise, evidence remains limited and inconsistent, and more research is needed before FMT can be considered a reliable therapeutic option in these settings.⁶¹ As research evolves, FMT may play a greater role in targeted microbiome therapy, but current evidence supports only limited applications.

While these therapeutic strategies highlight the promise of microbiome testing, there remain many challenges on the path to clinical adoption. Despite the growing enthusiasm, concerns remain that microbiome testing may be prematurely integrated into clinical care, risking misinterpretation and overinterpretation of findings. These risks arise when correlations are interpreted as causative, leading to inappropriate interventions based on unvalidated assumptions.⁴⁷ In the absence of validated clinical thresholds and regulatory oversight, some microbiome testing platforms communicate results in a way that frames dysbiosis as a diagnosis rather than a descriptive finding, contributing to confusion around its clinical relevance.^12,62

These concerns are further compounded by the variability in methods across different microbiome studies, which limits the reproducibility, reliability, and applicability of findings. Differences in sample collection, sequencing platforms, data preprocessing pipelines, and reference databases can significantly affect microbial community profiles, making it difficult to compare results across studies or translate them into clinical practice.⁶³ Another important confounding factor is variability between hosts. Factors such as diet, geography, and medications can significantly alter the microbiome.⁶⁴ These sources of variation reduce the generalizability of study findings.

The lack of standardized definitions and diagnostic criteria for dysbiosis further complicates the clinical application of microbiome testing. Studies of the human microbiome have revealed that individuals deemed to be “healthy” differ remarkably in the microbes that make up the microbiome.⁶⁵ This high degree of inter-individual variability makes it difficult to determine whether a given microbial pattern is truly abnormal or simply a reflection of natural variation. Without clear reference ranges or functional benchmarks, labeling a microbiome as imbalanced risks overdiagnosis and may lead to misguided interventions.²² As a result, two individuals with vastly different microbiome profiles may both be considered healthy, making it difficult to define what truly counts as dysbiosis in clinical practice.

Microbiome test results are often interpreted without sufficient clinical context, which can lead to misleading conclusions and inappropriate recommendations. Many testing platforms provide simplified interpretations of complex microbial data, suggesting specific dietary changes or supplements based solely on the presence or absence of certain bacteria.⁶⁶ At this time, there remains a lack of randomized controlled trials to support clinical microbiome recommendations, and the field continues to lack robust evidence linking specific microbial patterns to therapeutic outcomes.⁶⁶ This may lead both patients and clinicians to act on correlations rather than causation, potentially delaying or diverting care away from more appropriate evidence-based interventions.

When interpreting microbiome testing, an important consideration often overlooked is how rapidly the gut microbiota can change.⁶⁷ A person’s gut microbiota can shift significantly over short periods, sometimes within hours to days following dietary changes or antibiotic exposure, and over weeks to months in response to illness, stress, or broader lifestyle factors.^54,67 A single microbiome sequencing result may not accurately reflect an individual’s long-term microbial state or disease risk. This variability raises concerns about the reliability of using one-time microbial snapshots to guide clinical decision-making.

The direct-to-consumer (DTC) microbiome testing market has experienced rapid growth, fueled by increasing consumer demand for personalized health insights and a growing awareness of the gut microbiome’s role in overall wellness.⁶⁸ However, there is a risk that the commercial pressures to provide microbiome testing to consumers are outpacing the scientific evidence required to support their clinical validity. Many companies offer interpretations of microbiome test results and personalized dietary or supplement recommendations based on incomplete or unvalidated data.^68,69 Much of current DTC testing lacks standardization, clinical oversight, and reproducibility, which raises important questions about whether these platforms can reliably inform health-related decision-making.⁶⁸ This disconnect between commercial marketing and scientific evidence risks misleading consumers and can undermine trust when it comes to significant advances in microbiome science.

Microbiome testing has the potential to shape medical decision-making by giving us a clearer view of how the host and environment interact. Its applications span a variety of specialties where gut-skin interactions continue to generate clinical interest. In dermatology, this has prompted growing investigation into how microbial imbalance may contribute to inflammatory and autoimmune skin disease.

However, real-world use is limited by major challenges, including high person-to-person variability, methodological and study-design variability, and the lack of clear reference standards. To shift from correlation to true clinical value, the field needs validated biomarkers, long-term studies, and sequencing methods that can be reproduced across different settings and patient groups. Without clear diagnostic cutoffs and validated markers, it will remain difficult to utilize microbiome testing as a tool that can provide actionable guidance for clinical care.

To distinguish dysbiosis from normal variation, meaningful clinical thresholds must be established. Clear thresholds are also needed to separate true dysbiosis that requires action from normal variation between individuals. This work will need to be backed by independent validation, well-designed trials, and regulatory oversight that protects both scientific integrity and patient safety.

Progress in microbiome science depends on building a strong base of evidence and transparency to provide clinical relevance. Strong scientific foundations must be established before commercial expansion, as only then will microbiome testing be ready to serve as a reliable guide in clinical care.