Microbiome‐skin‐brain axis: A novel paradigm for cutaneous wounds

Abstract

Chronic wounds cause a significant burden on society financially, medically, and psychologically. Unfortunately, patients with nonhealing wounds often suffer from comorbidities that further compound their disability. Given the high rate of depressive symptoms experienced by patients with chronic wounds, further studies are needed to investigate the potentially linked pathophysiological changes in wounds and depression in order to improve patient care. The English literature on wound healing, inflammatory and microbial changes in chronic wounds and depression, and antiinflammatory and probiotic therapy was reviewed on PubMed. Chronic wound conditions and depression were demonstrated to share common pathologic features of dysregulated inflammation and altered microbiome, indicating a possible relationship. Furthermore, alternative treatment strategies such as immune-targeted and probiotic therapy showed promising potential by addressing both pathophysiological pathways. However, many existing studies are limited to a small study population, a cross-sectional design that does not establish temporality, or a wide range of confounding variables in the context of a highly complex and multifactorial disease process. Therefore, additional preclinical studies in suitable wound models, as well as larger clinical cohort studies and trials are necessary to elucidate the relationship between wound microbiome, healing, and depression, and ultimately guide the most effective therapeutic and management plan for chronic wound patients.

The Cutaneous Physiological Redox: Essential to Maintain but Difficult to Define

“…However, with the advancement of interdisciplinary research approaches, the importance of the human microbiome in the cross-talk between remote tissues as well as its influence on various organ systems have been emphasized. First, the phrase “gut–brain axis” was coined, followed by advanced derivatives such as the above mentioned “gut–brain–skin axis” and “microbiome–skin–brain axis” [ 64 , 65 , 66 ]. The gut–brain axis refers to a link between mental conditions (i.e., depression, anxiety, etc.)…”

“…The term was later coined and discussed further [ 67 , 71 ], while the molecular basis for this interesting relationship may most likely be attributed to stress-related neurotransmitters [ 72 ]. Most recently, Hadian et al [ 65 ] referred to the microbiome–skin–brain axis in the context of bacterial involvement in wound healing and it is psychological and mental effects. Clearly, the skin and its associated microbiome is highly involved in many systemic physiological and pathologic processes and its importance in overall health and disease becomes apparent, similarly to that of the gut microbiome.…”

Skin-brain axis signaling mediates behavioral changes after skin wounding

“…( Johnson et al., 2020 ), ( Bosurgi et al., 2017 ; Braune et al., 2017 ), ( Wood et al., 2011 ) Given our findings that serum IL6 was increased at 6 days post-wounding, this would suggest it is involved in regulating wound resolution. There is also extensive documentation of strong correlation of elevated IL6 serum levels in patients with major depressive disorder ( Hadian et al., 2020 ; Roohi et al., 2021 ). While the exact underpinnings of this association are not completely understood, one documented action of IL6 is the control of the level of the serotonin transporter, and subsequently serotonin uptake ( Kong et al., 2015 ).…”

“…Monoamines, especially dopamine, are essential for memory formation ( Wise, 2004 ) and altered CNS dopamine signaling has been associated with cognitive dysfunction in a number of diseases ( Calabresi et al., 2006 ; Braver and Cohen, 1999 ; Pan et al., 2019 ). Additionally, systemic levels of inflammatory cytokines have also been associated with cognitive deficits in patients with post-traumatic stress disorder, and major depressive disease ( Hadian et al., 2020 ; Imai et al., 2018 ; Roohi et al., 2021 ). We hypothesized that the affective and cognitive symptoms in subjects with chronic skin wounds associate with alterations in CNS monamines, or with systemic elevation of inflammatory cytokines, and sought to determine the signaling pathways between peripheral wounds and the central nervous system.…”

Self-Reported Impaired Wound Healing in Young Adults and Their Susceptibility to Experiencing Immune-Related Complaints

“…Chronic wounds are prevalent and constitute an underestimated public health problem [1,2]. In the United States, approximately 8.2 million adults are diagnosed with chronic wounds with or without infection, and the financial cost for chronic wound treatments have been estimated to range from $28 to $31 billion [3].…”