Human Microbiomes: Disease, Health, and Wound Healing

Altered Microbiome

The human microbiome consists of different microbial communities inhabiting the skin, gastrointestinal tract, and respiratory and other organ systems. The genetic diversity of the human microbiome is so immense that 90% of the cells in the human body are not human cells,¹ and non-human genetic material represents more than 98% of the total human genomic blueprint.² Most of these "other" microbes are commensals or symbiont bacteria, fungi, and phages that usually live in relative harmony within their human host. They even contribute metabolic pathways that we have not had to evolve that influence metabolism and drug interactions.² Through its involvement in immunity, inflammation, and metabolism, the human microbiome also plays an important role in the pathogenesis of specific diseases. For example, microbial imbalances or maladaptations, known as dysbiosis, of both the skin and gut microbiome can lead to the pathogenesis and progression of diabetes.³

Gut microbiome

The gut microbiome contributes almost 2kg of a person’s body weight.⁴ Links have been found between the microbiome of the gastrointestinal tract and autoimmune, metabolic, and atopic diseases, including metabolic syndrome and diabetes.^4,5 The linkage between the gut microbiome and disease is more than an altered environment and resources due to the disease state. Commensal flora, the organisms typically seen in the gut microbiota in those with diabetes, differs from those without diabetes,⁶ and it displays a distinctive inflammatory profile.⁷ The interaction between human cells, bacteria, fungi, and phages influences the microbiome's effect on human health and disease. Bacteriophages, viruses that infect bacteria, have been studied in the oral cavity and have been found to encode several virulence factors that influence the threshold between commensal organisms and pathogens that cause infection.⁸ The gut microbiome can also positively influence tissue repair, regeneration, and resilience to infection.⁹

Skin microbiome

Every square centimeter of human skin contains approximately one billion bacteria.¹⁰ Common commensal organisms include Corynebacteria, Propionibacteria, Staphylococci, and the fungus Malassezia.⁵ The communities that inhabit the skin microbiome vary based on location, with areas like the axilla, foot, or posterior auricular crease having unique genus and phylum level classifications of their communities.² They also vary based on genetics and environmental variables, with differences between urban and rural populations, age, and gender.¹¹ Commensal microbes on the skin maintain the epithelial barrier function, activate the immune system, and are a part of the first line of defense against pathogenic invasion.^3,5 Similar to findings with the gut microbiota, the skin microbiota in patients with diabetes differ from those without diabetes, which may contribute to the impaired wound healing of diabetic ulcers.³ Dysbiosis in the diabetic population’s skin microbiome may be partly due to alterations in the innate immune response,³ including the increased adherence of microbes and increased virulence.¹²

Wound microbiome

The wound microbiome is a dynamic environment that changes during healing. Like the skin microbiome, wound microbiomes vary based on wound etiology, comorbidities, location, and treatment. New genomic sequencing technologies and a broader taxonomic library have made wound genomic sequencing an opportunity outside of research and available in wound centers. Since culturing has existed, scientists can visualize more bacteria in terms of numbers and more diverse types of bacteria under a microscope than what they could culture on plates.² A genomic sampling of wounds provides more comprehensive taxonomic profiles of the biome compared with a wound culture.¹³ Limitations existed with this sampling technique in terms of assessing for infectious pathogens. Genomic wound analysis revealed a more comprehensive picture of microbial load within the wound but did not discriminate between what organisms were contributing to infection. With technological and research improvements, we are continuing to understand not only what microbes are within the wound but also what virulence and antibiotic resistance genes they contain.

Outside of their role in infection, the interaction between human cells, pathogens, and commensals of the microbiome also has impacted wound healing. High levels of oxidative stress, which occurs in many chronic wounds, decrease the diversity of wound microbiota and promote the formation and maturation of biofilm.¹⁴ These organisms not only react to an inflammatory environment but also participate in the inflammatory response.⁵ When skin is injured, microbiota that was previously commensally living on the epidermis is moved to the exposed dermis, where they have been found to trigger neutrophil activation and initiate early wound repair response.¹⁵ Recent research has studied the microbiome of the diabetic foot as a method of predicting healing, with marked differences in wounds that do not progress to closure compared with wounds that heal.¹⁴ Destabilizing cutaneous microbiota in nonhealing wounds through methods like debridement and non-contact, low-frequency ultrasound can transition wounds to a healing trajectory. Though current antimicrobial practices in wound healing focus on eliminating harmful bacteria, the future practice of precision medicine may entail sampling wounds and selectively adding or eliminating microbes to facilitate healing.

Conclusion

References

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