Microbiomes, OA, and Diabetic Foot Ulcers

This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson. 

We hear the term “microbiome” with increasing frequency nowadays. Merriam-Webster’s online dictionary defines it as “a community of microorganisms (such as bacteria, fungi, and viruses) that inhabit a particular environment and especially the collection of microorganisms living in or on the human body.” Two recent studies suggest how the microbiome can affect musculoskeletal health.

Incorporating the term “the arthritis of obesity,” Rochester, New York researchers¹ used obese mice with trauma-induced knee osteoarthritis (OA) to provide evidence that there is a “gut-joint connection” in the OA degenerative process. After supplementing the diets of some of the mice with oligofructose (a prebiotic fiber), the authors found reduced systemic inflammation, reduced obesity-associated macrophage migration to the synovium, and suppressed obesity-induced joint-structure changes.

Another recent study investigated the on-body microbiome as it relates to diabetic foot ulcers (DFUs). Despite clinical signs and nonspecific biomarkers of infection, there is no specific and sensitive measure available to monitor or prognosticate the success of foot salvage therapy (FST) in patients with DFUs. These investigators hypothesized that the initial microbiomes of healed versus nonhealed DFUs are distinct and that the changes in the DFU microbiome during FST are prognostic of clinical outcome.²

Twenty-three DFU patients undergoing FST had wound samples collected at 0, 4, and 8 weeks following wound debridement and antibiotic treatment. Eleven ulcers healed and 12 did not. Healed DFUs had a larger abundance Actinomycetales and Staphylococcaceae (p < 0.05), while nonhealed ulcers had a higher abundance of Bacteroidales and Streptococcaceae (p < 0.05).

In the future, assessment of the initial microbiome and monitoring changes in the prevalence of specific microbiome constituents in patients with diabetic foot ulcers may be a clinical tool for predicting treatment response to foot salvage therapy. It’s also conceivable that microbiome analysis could eventually help patients and surgeons decide between FST and amputation.

References

1. Schott EM, Farnsworth CW, Grier A, Lillis JA, Soniwala S, Dadourian GH, Bell RD, Doolittle ML, Villani DA, Awad H, Ketz JP, Kamal F, Ackert-Bicknell C, Ashton JM, Gill SR, Mooney RA, Zuscik MJ. Targeting the gut microbiome to treat the osteoarthritis of obesity. JCI Insight. 2018 Apr 19;3(8). pii: 95997. doi: 10.1172/jci.insight.95997. [Epub ahead of print] PMID: 29669931, PMCID: PMC593113
2. MacDonald A, Brodell JD Jr, Daiss JL, Schwarz EM, Oh I. Evidence of differential microbiomes in healing versus non-healing diabetic foot ulcers prior to and following foot salvage therapy. J Orthop Res. 2019 Mar 25. doi: 10.1002/jor.24279. [Epub ahead of print] PMID: 30908702