Microbiome: Our opponents or allies in healthcare and medicine

Addressing the presence of unwanted bacteria and fungi following medical procedures has long been a major healthcare concern. Infection applications can range from wounds, to surgical sites to biomedical implants. Current strategies employ strong, broad-spectrum antibiotics as a prophylactic prior to any planned procedure, and aggressive antimicrobial therapies following detection of any unwanted organism. For decades, the only strategy for an infected implant showing presence of a bacterial biofilm was removal of the implant.^1–4 However, recent knowledge and growth in the field of microbiome and mycobiome detecting the presence of organisms even in “uninfected” implants⁵ and normal tissue⁶ demonstrate that new strategies can be employed which don't necessarily need to eradicate all bacteria and fungi, but could be geared toward restoring homeostasis in the organism.^7,8 This Special Issue broadly addresses new knowledge in microbiome-related research, particularly in regards to medicine and healthcare. We hope it can serve as a state-of-the-art review of recent advances, suitable for experts in the field, as well as a primer for the novice to understand what areas are involved and gain a rapid understanding of how these different topics have come together.

The microbiome is described as the ecological community of commensal, symbiotic and pathogenic microorganisms (microbiota), or the collective genome of such organisms. The term first appeared in a PubMed cited article in 1956 but was used to describe microbial communities in non-medical applications.⁹ Over the next several decades, the microbiome field grew steadily with an exponential explosion beginning around 2000 due, in part, to advancement of high-throughput computational and genomic techniques (Figure 1, “microbiome”). Knowledge of the microbiome in medicine, particularly in regards to gut flora has also been extensively investigated, and underwent a similar exponential growth, starting around 2009 (Figure 1, “microbiome AND medicine”). Understanding how manipulation of microbiome for healthcare broadly, such as in the treatment of wound management (Figure 1, “microbiome AND healthcare”) as well as more specifically, such as in the treatment of implant infection (Figure 1, “microbiome AND implant”) are fields that are in their infancy, with only a handful of citations each.

Figure 1.

Histogram of Pubmed articles on “microbiome”. While “microbiome” (diamonds) has shown as steady gain since it first appeared in a PubMed cited article in 1956, the field began to see an exponential rise in 2000. Concatenation with other terms such as “medicine” (squares), “healthcare” (triangles) and “implant” (X's) show much later appearances.

In the case of implant infection, certain of certain organisms (e.g. Staphylococcus aureus, Staphylococcus epidermidis) have long been known to generate sufficient cytotoxic and inflammatory signals, ultimately leading to implant failure. These organisms have been consistently identified due to the high prevalence cultured out of infected implants. While single organisms are often pointed to as the culprits, infections are typically presumed to not be monoclonal. Indeed, other organisms, such as Propionibacterium acnes, have often been identified with implant infections, but their role as co-infectant (e.g. arriving either before S. aureus or after) has not been made clear.¹⁰ In other cases, chronic “low grade” infections have been observed, in which microbial organisms are present but inflammatory processes have not been activated sufficient to result in implant failure.¹¹

While the capacity to culture and grow bacteria has existed for over 100 years, until recently, only a sampling of the species present in an implant infection have been able to be identified. This is likely due to slow or difficult culture conditions needed (including anaerobic bacteria), as well as organisms present in such low copy number that only high-resolution PCR and computational techniques were capable of identifying them.⁵

In this Special Issue on Microbiome in Healthcare and Medicine, we investigate multiple aspects of the study of microbiomes ranging from the development of standardized protocols for studying microbiome in animal models, by Rodriquez-Palacios et al.,¹² to aspects in either treating the organism directly,¹³ or indirectly by treating the consequences, such as inflammation by von Recum et al.¹⁴

We started off with a pair of broad review topics, the first on understanding the role of microbiome in diet and health by McDonald et al.,¹⁵ and the second on new strategies to engineer microbiome and understanding its impact on health by Son et al.¹⁶ Then a group of reviews examines our understanding of microbiome and disease as Jacobs et al. show how gut microbiome plays a role in fatty liver disease, a condition not traditionally thought of as infectious in origin.¹⁷ In Skondra et al., we learn how microbiome could play a role in a broad range of ophthalmic disease,¹⁸ while in Yacoub et al., we learn about how the microbiome plays a role in the development of cardiovascular disease during chronic kidney disease.¹⁹ On the computational side, Shen et al. review recent progress on elucidating the complex interactome between various microbial players to better understand the microbiome network.²⁰ Oliveira et al. combine computation and detective work to identify and track microbiota in healthcare environments.²¹ We are rounded out by a pair of original research articles: Parker et al. study the microbiota in mole-rats to understand the roles they play in diet and evolution,²² while Yacoub et al. analyze fecal microbiota in patients with polycystic kidney disease.²³

Wherever biomedical research takes us, it is clear that the “reset” button provided by antibiotics will not be the only tool in our arsenal to treat healthcare associated infections. Future research will lead to better understanding of the microbiome and how to restore homeostasis of the biological community, followed by targeted approaches to biofilm eradication and/or the treatment of inflammation as the consequence of infection.

DECLARATION OF CONFLICTING INTERESTS

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

FUNDING

The author(s) received no financial support for the research, authorship, and/or publication of this article.