The Role of the PFNA Operon of Bifidobacteria in the Recognition of Host’s Immune Signals: Prospects for the Use of the FN3 Protein in the Treatment of COVID-19

Abstract

Bifidobacteria are some of the major agents that shaped the immune system of many members of the animal kingdom during their evolution. Over recent years, the question of concrete mechanisms underlying the immunomodulatory properties of bifidobacteria has been addressed in both animal and human studies. A possible candidate for this role has been discovered recently. The PFNA cluster, consisting of five core genes, pkb2, fn3, aaa-atp, duf58, tgm, has been found in all gut-dwelling autochthonous bifidobacterial species of humans. The sensory region of the species-specific serine-threonine protein kinase (PKB2), the transmembrane region of the microbial transglutaminase (TGM), and the type-III fibronectin domain-containing protein (FN3) encoded by the I gene imply that the PFNA cluster might be implicated in the interaction between bacteria and the host immune system. Moreover, the FN3 protein encoded by one of the genes making up the PFNA cluster, contains domains and motifs of cytokine receptors capable of selectively binding TNF-α. The PFNA cluster could play an important role for sensing signals of the immune system. Among the practical implications of this finding is the creation of anti-inflammatory drugs aimed at alleviating cytokine storms, one of the dire consequences resulting from SARS-CoV-2 infection.

Biomarkers and Utility of the Antioxidant Potential of Probiotic Lactobacilli and Bifidobacteria as Representatives of the Human Gut Microbiota

“…The antioxidant properties of probiotics based on lactobacilli and bifidobacteria remain underestimated in this field [212]. For instance, the FN3 protein derived from B. longum GT15 has been shown to selectively bind to tumor necrosis factor alpha (TNF-α) [213,214]. New perspectives emerge for the use of components of lactobacilli and bifidobacteria, rather than using them as live cultures.…”

Common Inflammatory Mechanisms in COVID-19 and Parkinson’s Diseases: The Role of Microbiome, Pharmabiotics and Postbiotics in Their Prevention

“…Analysis of the state of the microbiome is an important biomarker of the state of the immune and nervous system and susceptibility to neurological and infectious diseases as COVID-19. 32,393,394 The intestinal microbiome influences the host organism due to its ability to synthesize various biologically active compounds. The whole system functions as a single network.…”

Alterations of the Composition and Neurometabolic Profile of Human Gut Microbiota in Major Depressive Disorder

“…In agreement with previous reports [ 76 ], an abundance of the genus Bifidobacterium was non-significantly increased in PwD metagenomes. Bifidobacteria are known to exhibit probiotic properties and, recently, it has been proposed as a ‘psychobiotic,’ given its ability to produce neuromodulators and influence gut–brain relationships through interactions with other commensal bacteria [ 77 , 78 , 79 , 80 , 81 ]. The reason for these contradicting results remains unclear and requires further research.…”