Long Covid, the Gut, and Autoimmune Skin Diseases: A Novel Therapeutic Approach

Abstract

The dermatological manifestations of Long Covid (LC) have languished in the shadows of chronic fatigue and brain fog. Yet they are all linked by gut dysbiosis and the cytokine triad of TNF-α, IL-1β, and IL-6. The gut microbiome common not only to LC, psoriasis, AA, and vitiligo but also to neurodegenerative disease has been recently described. This gut microbiome induces an altered tryptophan metabolism linked to autoimmune disease. SARS CoV2, Mycobacteria, and many intestinal parasites protectively upregulate IFN-γ (less Covid in BCG and in subSaharan Africa), triggering the characteristic altered tryptophan metabolism and curtailing synthesis of serotonin and melatonin. Chronic inflammation due to persistent spike protein S exhausts IFN-γ and leads to gut dysbiosis and autoimmune risk. Butyrate immunomodulates IFN-γ and TGF-β, which counterbalance each other (reciprocal relationship). Low IFN-γ (LC) translates to high TGF-β (organ fibrosis). This review suggests that an etiologic prebiotic (d-mannose)/probiotic (lactobacilli, bifidobacteria)/postbiotic (butyrate) approach to autoimmune skin disease that improves intestinal barrier integrity and that suppresses the triad of TNF-α, IL-6, and IL-1β may enhance or even eliminate the traditional immunotherapy of targeted monoclonal antibodies, Janus kinase inhibitors, and steroids. Health benefits of this approach extend well beyond suppression of autoimmune skin disease. Societal benefits include relief to those most affected - women (LC), especially of color (AA, psoriasis, vitiligo).