Precision Postbiotics and Mental Health: the Management of Post-COVID-19 Complications

Abstract

The health catastrophe originated by COVID-19 pandemic construed profound impact on a global scale. However, a plethora of research studies corroborated convincing evidence conferring severity of infection of SARS-CoV-2 with the aberrant gut microbiome that strongly speculated its importance for development of novel therapeutic modalities. The intense exploration of probiotics has been envisaged to promote the healthy growth of the host, and restore intestinal microecological balance through various metabolic and physiological processes. The demystifying effect of probiotics cannot be defied, but there exists a strong skepticism related to their safety and efficacy. Therefore, molecular signature of probiotics termed as "postbiotics" are of paramount importance and there is continuous surge of utilizing postbiotics for enhancing health benefits, but little is explicit about their antiviral effects. Therefore, it is worth considering their prospective role in post-COVID regime that pave the way for exploring the pastoral vistas of postbiotics. Based on previous research investigations, the present article advocates prospective role of postbiotics in alleviating the health burden of viral infections, especially SARS-CoV-2. The article also posits current challenges and proposes a futuristic model describing the concept of "precision postbiotics" for effective therapeutic and preventive interventions that can be used for management of this deadly disease.

Keywords: Dysbiosis; Gut microbiome; Gut-brain axis; Postbiotics; Probiotics; SARS-CoV-2.

Fig. 1

Conception, timeline development, and applications of postbiotics

Fig. 2

Modulation of intestinal barrier integrity by various postbiotics (schematic illustration depicting the action of various postbiotic molecules affecting intestinal barrier functions) (red arrow representing the upregulation of various signaling pathways by various postbiotic molecules while blue arrow representing the downregulation of signaling pathways). AMPs, antimicrobial peptides; AP-1, activating protein; CSP, capsular polysaccharide; IECs, intestinal epithelial cells; HIF, hypoxia-inducible factor; GPCRs, G-protein-coupled receptors; AhRs, aryl hydrogen receptors; P75 and P40, cell wall–associated hydrolase; EGFR, epidermal growth factor receptor; PI3K, phosphatidylinositol-3-kinase; PXR, pregnane X receptor; APRIL, a proliferation-inducing ligand; Hsp72 and Hsp25, heat shock proteins; ZO-1, zona occludin,1; IPA, indole 3-propionic acid; TEER, transepithelial electrical resistance; TJPs, tight junction proteins; TLR, toll-like receptors

Fig. 3

Modulation of innate and adaptive immunity by various postbiotics (schematic illustration depicting the action of various postbiotic molecules affecting innate and adaptive immunity) (red arrow representing the upregulation of various signaling pathways by various postbiotic molecules while blue arrow representing the downregulation of signaling pathways; green arrow representing the reduction of postbiotic molecules after binding of SARS-CoV-2 with ACE-2 receptor) ACE2, angiotensin-converting enzyme; B₀AT1, amino acid transporter; NOD, nucleotide-binding oligomerization domain2 (NOD-2); IDO, indoleamine 2,3-dioxygenase; NKT, natural killer T; NRP-neuropilin; mTOR, mammalian target of rapamycin; PKA, protein kinase A; HD-5, human defensin-5; GPRs, G-protein receptors; IL, interleukin; IFN, interferon; JAK/STAT, Janus kinase/signal transducers and activators of transcription; MCP-1, monocyte chemoattractant protein,1; G-CSF, granulocyte colony-stimulating factor; IP-10, interferon gamma-induced protein 10; MIP-1A, macrophage inflammatory protein,1; VDR, vitamin D receptor

Fig. 4

Postbiotics in balancing hypothalamic–pituitary–adrenal axis and mental health during post-COVID regime (schematic illustration depicting the action of various postbiotic molecules affecting mental health) (red arrow representing the upregulation of various signaling pathways by various postbiotic molecules while blue arrow representing the downregulation of signaling pathways) BDNF, brain-derived neurotrophic factor; DA, dopamine; 5-HT, 5-hydroxytryptamine or serotonin; BZA, benzoic acids; dgk, diacylglycerol kinase; EPS, exopolysaccharide; GABA, gamma-Aminobutyric acid; GLP-1, glucagon-like peptide,1; Glu, glutamate or glutaminergic; H₂O₂, hydrogen peroxide; HPA, hypothalamic–pituitary–adrenal axis; IECs, intestinal epithelial cells; IDO, indoleamine 2,3-dioxygenase; IL-6, interleukin-6; KYN, kynurenine; NE, norepinephrine; ROS, reactive oxygen species; SCFA, short-chain fatty acid; Tph1, tryptophan hydroxylase 1; TRP, tryptophan

Fig. 5

Proposed model for the development of precision postbiotics to be used in the management of COVID-19 pandemic