Microbiome Transplants for Skin, Lung, and Metabolic Diseases

By Dr. Chinta SidharthanReviewed by Benedette Cuffari, M.Sc.

Introduction
The skin microbiome as a therapeutic target
Targeting lung disease through microbiome modulation
Gut microbiome interventions for metabolic disease
Safety and regulatory challenges
Future directions for microbiome therapeutics
References
Further reading

From skin inflammation and chronic lung disease to obesity and diabetes, researchers are uncovering how targeted microbiome interventions could reshape disease treatment by harnessing the therapeutic power of the body's microbial ecosystems.

Image Credit: Kateryna Kon / Shutterstock.com

Introduction

The human body harbors trillions of microorganisms across its surfaces and cavities that support immune function, metabolism, and protection against pathogens. Dysbiosis in these microbiomes is associated with, and in some contexts contributes to,^1,2 inflammatory, metabolic, and infectious diseases, which has led to growing interest in microbiome-based therapies (MBTs) as strategies to restore microbial balance and improve health outcomes. Microbiome transplantation is best established for recurrent Clostridioides difficile infection, while applications in skin, lung, and metabolic disease remain more experimental and disease-specific.²

The skin microbiome as a therapeutic target

Human skin can be further divided into moist, dry, and sebaceous sites, each of which is characterized by a distinct microbial profile. Whereas sebaceous skin is dominated by cutibacteria and staphylococci, moist sites are rich in Corynebacterium and Staphylococcus species. Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes are among the dominant bacterial phyla on human skin, while fungal communities are often dominated by Malassezia.⁵

Regardless of the type or location, the skin microbiome composition typically remains stable over time; however, strain-level differences have been observed in several dermatological conditions. In atopic dermatitis, strong correlations between flares and increased S. aureus abundance have been reported, and these alterations are corrected with biologics such as dupilumab that target excessive immune responses. Microbiome alterations have also been described in psoriasis, acne, hidradenitis suppurativa, diabetic foot ulcers, and some skin cancers, although causal roles vary by condition.⁵

Moreover, the presence of specific fungi, such as Malassezia furfur and M. globosa, on the scalp is characteristic of dandruff, along with an imbalance in Cutibacterium and Staphylococcus species⁴.

Collectively, these observations suggest that manipulating the skin microbiome could represent a viable therapeutic strategy for several dermatological disorders.

For example, a skin microbiome transplant involves transferring the skin microbiome of a healthy individual to the washed and/or disinfected skin area of another individual. Prior to transplantation, culturing healthy skin microorganisms is essential to ensure sufficient bacteria are applied. However, complete donor-community transplantation is still less clinically developed than targeted application of selected commensal strains.^4,5

Skin bacteriotherapy has also been investigated using probiotics, postbiotics, purified bacterial enzymes, or fermentation products. Compared with skin microbiome transplantation, skin bacteriotherapy is considered more scalable, as a single highly concentrated culture can be applied, potentially achieving greater efficacy than a more diverse, diluted donor sample⁴.  

Early clinical studies have begun to evaluate the therapeutic potential of these approaches in patients with various inflammatory skin disorders. Topical commensal approaches, including antimicrobial Staphylococcus hominis strains in atopic dermatitis and selected Cutibacterium acnes strain mixtures in acne-prone skin, have shown early safety and microbiome-modulating signals, but larger controlled trials are needed before routine clinical use.^4,5

Targeting lung disease through microbiome modulation

The lungs have historically been considered sterile organs; however, culture-independent sequencing has established that the lower respiratory tract harbors a distinct microbial community, dominated under non-diseased conditions by Streptococcus, Prevotella, and Veillonella.^3,6 In chronic respiratory disease and lung transplant recipients, this balance shifts toward pathogenic taxa due to impaired trapping and clearance of particles by the mucous layer, microaspiration of contents from the oropharyngeal tract, or immunosuppression.^3,6,7

Although direct lung microbiome intervention remains largely unexplored, the gut-lung axis provides a biological rationale for targeting pulmonary diseases through intestinal modulation. Specifically, these modulation strategies include dietary fiber supplementation, probiotics, bacteriophage therapy targeting specific pathogens, and antibacterial monoclonal antibodies.^3,7 In lung transplantation, microbiome-targeted interventions remain investigational and have not yet been clearly linked to improved patient-centered outcomes.⁶ Thus, current lung approaches are better described as microbiome modulation rather than true lung microbiome transplantation.^6,7

Short-chain fatty acids (SCFAs) like acetate, propionate, and butyrate are produced by anaerobic gut bacteria through dietary fiber fermentation. SCFAs promote regulatory T-cell differentiation and control innate lymphoid cell activity, with animal studies reporting that SCFAs protect against bacterial pneumonia and allergic airway inflammation.^6,7 Bacteriophage therapies that target multidrug-resistant Pseudomonas aeruginosa have also been used to treat infections in cystic fibrosis and ventilator-associated pneumonia, with promising results advancing into formal clinical trials.⁷

These interventions are associated with numerous limitations, including small sample sizes, cohort heterogeneity in lung transplant research, and unpredictable engraftment rates.^5,6 The lung microbiome is associated with unique challenges due to its low bacterial biomass, with 10³-10⁵ bacteria/gram of tissue as compared to 10¹¹ in the gut. Moreover, the metabolic potential of the lung microbiome remains largely uncharacterized.³ Recent genome-mining work suggests that lung-associated bacteria and fungi encode diverse biosynthetic gene clusters, indicating that the lung microbiome may be a source of specialized metabolites with possible roles in microbial competition, host interaction, and drug discovery.³

Image Credit: VetorMine / Shutterstock.com

Gut microbiome interventions for metabolic disease

Potential therapies for metabolic diseases are also being explored through gut-based approaches, given the central role of the gut microbiome in energy metabolism and immune regulation. Specifically, the gut microbiome regulates metabolic pathways through insulin signaling, bile acid metabolism, and lipogenesis. Microbial metabolites, including SCFAs, amino acids, vitamins, bile acid derivatives, and inflammatory microbial products such as lipopolysaccharide, can influence host immunometabolism.¹

In patients with obesity and type 2 diabetes, beneficial microbial taxa like Akkermansia muciniphila and Faecalibacterium prausnitzii are depleted, while obese individuals often exhibit a low Bacteroidetes/Firmicutes ratio.¹ Translocation of gut microbiota-derived lipopolysaccharide into circulation during dysbiosis initiates low-grade inflammatory endotoxemia, ultimately leading to obesity-related metabolic syndrome. These inflammatory signals can affect tissue-resident macrophages and immune-cell metabolism, including pathways linked to pro-inflammatory M1 and anti-inflammatory M2 macrophage states.¹

Restoring A. muciniphila abundance in the gut in obesity models has been shown to improve metabolic parameters.¹ However, engraftment, which describes the stable establishment of transplanted organisms in the recipient microenvironment, remains a significant challenge, with success rates varying across individuals based on donor-recipient microbiota compatibility and host immune factors.²

Comparatively, gut microbe-derived butyrate promotes insulin sensitivity, whereas propionate acts as a hepatic gluconeogenic factor. In fact, metformin, which is used to treat type 2 diabetes, partly mediates its therapeutic effects through microbiome modulation by promoting butyrate-producing bacteria.¹ For metabolic disease, microbiome therapies are therefore better described as promising adjunctive strategies rather than established replacements for diet, exercise, and pharmacological treatment.^1,2 Dietary fiber, prebiotics, probiotics, synbiotics, and selected small molecules are also being investigated as ways to reshape microbial metabolism without whole-community transplantation.¹

Safety and regulatory challenges

Although the field of microbial transplantation therapy has rapidly advanced, crucial safety concerns persist. In one study involving FMT from a screened donor, two immunocompromised patients developed bacteremia from extended-spectrum beta-lactamase-producing Escherichia coli, prompting mandatory enhanced pathogen testing protocols and significantly reducing the pool of eligible donors.²

In lung microbiome modulation studies, the risk of introducing live microorganisms to immunosuppressed transplant recipients prevents direct microbial introduction into the lower respiratory tract.⁶ Live biotherapeutic products require the same rigorous clinical trial infrastructure as conventional pharmaceuticals, including demonstration of safety, efficacy, and manufacturing reproducibility, which adds regulatory complexity.⁵

Similar concerns about potential co-transfer of pathogenic taxa alongside intended beneficial organisms have been described for skin transplantation therapies.⁵ Additionally, regardless of how the skin microbiome is disinfected before treatment, it remains difficult to ensure that all microbiota present throughout subcutaneous tissues have been eliminated. As a result, new microbiota applied to the skin epidermis directly compete with endogenous microorganisms for nutrients, thereby preventing successful engraftment and limiting the efficacy of available interventions.

Engineered bacterial strains carrying recombinant therapeutic genes face additional requirements regarding genetic stability and ecological containment. Factors such as administration routes, dosing schedules, antibiotic pretreatment protocols, and outcome assessment metrics vary substantially across studies, further limiting cross-trial interpretation.²

Future directions for microbiome therapeutics

Microbial dysbiosis in various tissues throughout the body contributes to disease development due to immune dysregulation, metabolic dysfunction, and pathogen overgrowth. Targeted microbiome interventions can reverse these processes, as demonstrated by high success rates of FMT for the treatment of recurrent Clostridioides difficile infection, with more variable and still-emerging evidence in metabolic syndrome and inflammatory bowel disease.²

Transitioning these strategies from the laboratory into the clinic requires a better understanding of the specific metabolic and immunological functions of these distinct microbiomes, as well as more rigorously designed clinical trials that account for substantial confounding factors. Future approaches are likely to move from whole-community transfer toward defined microbial consortia, engineered commensals, postbiotics, and metabolite-based interventions with clearer mechanisms and safety controls.^2,5

References

1. Belizário, J. E., Faintuch, J., & Garay-Malpartida, M. (2018). Gut Microbiome Dysbiosis and Immunometabolism: New Frontiers for Treatment of Metabolic Diseases. Mediators of Inflammation. DOI: 10.1155/2018/2037838. https://www.hindawi.com/journals/mi/2018/2037838/
2. Junca, H., Pieper, D. H., & Medina, E. (2022). The emerging potential of microbiome transplantation on human health interventions. Computational and Structural Biotechnology Journal 20; 615-627. DOI: 10.1016/j.csbj.2022.01.009. https://spj.science.org/doi/10.1016/j.csbj.2022.01.009
3. Semmler, F., Regis Belisário-Ferrari, M., Kulosa, M., & Kaysser, L. (2024). The Metabolic Potential of the Human Lung Microbiome. Microorganisms 12(7); 1448. DOI: 10.3390/microorganisms12071448. https://www.mdpi.com/2076-2607/12/7/1448.
4. Callewaert, C., Knödlseder, N., Karoglan, A., et al. (2021). Skin microbiome transplantation and manipulation: Current state of the art. Computational and Structural Biotechnology Journal 19; 624-631. DOI: 10.1016/j.csbj.2021.01.001. https://spj.science.org/doi/10.1016/j.csbj.2021.01.001
5. Madaan, T., Doan, K., Hartman, A., et al. (2024). Advances in Microbiome-Based Therapeutics for Dermatological Disorders: Current Insights and Future Directions. Experimental Dermatology 33(12). DOI: 10.1111/exd.70019. https://onlinelibrary.wiley.com/doi/10.1111/exd.70019
6. Combs, M. P. (2026). Microbiota and immune regulation in lung transplantation. Current Transplantation Reports 13, 9. DOI: 10.1007/s40472-026-00502-1. https://link.springer.com/article/10.1007/s40472-026-00502-1.
7. Mindt, B. C., & DiGiandomenico, A. (2022). Microbiome Modulation as a Novel Strategy to Treat and Prevent Respiratory Infections. Antibiotics 11(4), 474. DOI: 10.3390/antibiotics11040474. https://www.mdpi.com/2079-6382/11/4/474.  

Further Reading

• All Microbiome Content
• How Gut Fungi and Archaea Influence Human Health
• The Gut–Brain–Skin Axis: How Diet and Gut Health Influence Mood, Skin, and Aging
• Ovarian Microbiome Overview: Fertility, PCOS, and the Gut–Ovary Axis
• Scalp Microbiome Explained: What’s Living on Your Scalp and Why It Matters

Last Updated: Jun 23, 2026