Hidradenitis Suppurativa and 1-Carbon Metabolism: Role of Gut Microbiome, Matrix Metalloproteinases, and Hyperhomocysteinemia

Abstract

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin condition characterized by painful nodules which suppurate and later develop into scar tissues followed by the development of hypodermal tracts. Although the mechanisms behind HS are not fully understood, it is known that dietary factors play important roles in flare frequency and severity. We hypothesize that the high fat diet (HFD) causes dysbiosis, systemic inflammation, and hyperhomocysteinemia (HHcy) in susceptible individuals, which subsequently elevate inflammatory cytokines such as IL-1β, IL-6, IL-17, and tumor necrosis factor alpha (TNF-α). This increase in dysbiosis-led inflammation coupled with a dysregulation of the 1-carbon metabolism results in an increase in matrix metalloproteinases MMP-2, MMP-8, and MMP-9 along with tissue matrix remodeling in the development and maintenance of the lesions and tracts. This manuscript weaves together the potential roles played by the gut microbiome, HHcy, MMPs, and the 1-carbon metabolism toward HS disease causation in susceptible individuals.

Rebuilding Microbiome for Mitigating Traumatic Brain Injury: Importance of Restructuring the Gut-Microbiome-Brain Axis

“…They have shown that 72 h of post-injury was associated with a decrease in Bacteroidales, Fusobacteriales, and Verrucomicrobiales but an increase in Clostridiales and Enterococcus populations [149]. These findings provide the complex relation between and multiple disease outcomes, revealing the notion that bacterial populations indeed influence the post-injury mediated neuro-pathophysiology and functional impairment via dysbiosis-dependent mechanisms [150][151][152][153][154][155][156].…”

“…The eubiotic gut is closely linked with good human health, and an imbalance of the GM either because of HHcy-led dysfunction of the 1-carbon metabolism or any other reason is associated with various system disorders (Figs. 1 and 2 ) [ 150 , 153 – 156 , 192 – 194 ]. Because of the importance of bi-directional relationship between the GM and TBI-associated pathophysiology, management of gut dysbiosis could serve as paradigm for a likely therapeutic target (Figs.…”

“…Many of these deleterious effects could be mitigated by timely probiotics treatment. Abbreviations: TBI [150,[153][154][155][156][192][193][194]. Because of the importance of bidirectional relationship between the GM and TBI-associated pathophysiology, management of gut dysbiosis could serve as paradigm for a likely therapeutic target (Figs.…”

Impact of gut microbiome on skin health: gut-skin axis observed through the lenses of therapeutics and skin diseases

“…Gut microbial dysbiosis can potentially induce HS by influencing skin microbes through mediating systemic inflammatory pathways. 2 , 215 According to an interesting hypothesis, colonic dysbiosis resulting from high-fat diet results in inflammatory cytokine (e.g., TNF-α, IL-1β, and IL-17) elevation, and ultimately in formation of HS lesion by enhancing matrix metalloproteinase levels. 215 Probiotics are considered an effective option in treating HS for restoring a healthy cutaneous microbiome, as they are capable of replenishing the abundance of Cutibacterium spp., Corynebacterium , and Staphylococcus within the communities.…”

The Clinical Relevance of the Microbiome in Hidradenitis Suppurativa: A Systematic Review

“…It has been hypothesised that enteric dysbiosis (potentially caused by a high-fat diet) elevates inflammatory cytokines such as Il-1β, Il-17, and TNF-α. This ultimately leads to an increased level of matrix metalloproteinases and subsequently HS lesion formation in susceptible individuals [105].…”