ROLE OF GUT MICROBIOME HOMEOSTASIS, INTEGRITY OF THE INTESTINAL EPITHELIAL CELLS, AND THE (ENDOGENOUS) BUTYRATE IN ENDURING A HEALTHY LONG LIFE.

The influence of gut microbiomes on health has been gaining significance lately. More emphasis is their role in neurological illnesses as several of the metabolites and factors produced by the gut affect the brain via the gut-brain axis. Among all the gut microbiome produced metabolites, butyrate has been considered the most significant. Externally supplemented butyrate though has health benefits, when evaluated thoroughly, it is understood that there have been different pathways involved in the production of butyrate by the gut microbiome with the produced butyrate even being detrimental, though majority are beneficial. Importantly maternal butyrate supplementation has resulted in detrimental effects in the offspring. In this background, a black yeast Aureobasidium pullulans produced biological response modifier beta glucans (BRMGs) has shown beneficial outcome (anti-inflammatory: decrease in IL-6, Ferritin, C-reactive protein in COVID-19, D-Dimer; anti-fibrotic in fatty liver disease; improvement of behaviour and sleep with increase in α-synuclein, melatonin in autism) along with its effect on increasing the butyrate producing bacteria in the gut. Since only advantageous outcome has been reported with this BRMG produced butyrate, it is worth being considered as a yardstick for evaluation of exogenously supplemented and endogenous produced butyrate for their differential effects on host and its offspring.

A New Butyrate Releaser Exerts a Protective Action against SARS-CoV-2 Infection in Human Intestine.

Butyrate is a major gut microbiome metabolite that regulates several defense mechanisms against infectious diseases. Alterations in the gut microbiome, leading to reduced butyrate production, have been reported in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A new butyrate releaser, useful for all the known applications of butyrate, presenting physiochemical characteristics suitable for easy oral administration, (N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA), has been recently developed. We investigated the protective action of FBA against SARS-CoV-2 infection in the human small intestine and enterocytes. Relevant aspects of SARS-CoV-2 infection were assessed: infectivity, host functional receptor angiotensin-converting enzyme-2 (ACE2), transmembrane protease serine 2 (TMPRSS2), neuropilin-1 (NRP1), pro-inflammatory cytokines expression, genes involved in the antiviral response and the activation of Nf-kB nuclear factor (erythroid-derived 2-like) 2 (Nfr2) pathways. We found that FBA positively modulates the crucial aspects of the infection in small intestinal biopsies and human enterocytes, reducing the expression of ACE2, TMPRSS2 and NRP1, pro-inflammatory cytokines interleukin (IL)-15, monocyte chemoattractant protein-1 (MCP-1) and TNF-α, and regulating several genes involved in antiviral pathways. FBA was also able to reduce the number of SARS-CoV-2-infected cells, and ACE2, TMPRSS2 and NRP1 expression. Lastly, through the inhibition of Nf-kB and the up-regulation of Nfr2, it was also able to reduce the expression of pro-inflammatory cytokines IL-15, MCP-1 and TNF-α in human enterocytes. The new butyrate releaser, FBA, exerts a preventive action against SARS-CoV-2 infection. It could be considered as an innovative strategy to limit COVID-19.

Analysis of 2D nanomaterial BC3 for COVID-19 biomarker ethyl butyrate sensor.

Ethyl butyrate (EB) was identified in recent research as a prominent biomarker of COVID-19, as concentrations of EB were higher in exhaled breath of COVID-19 patients. Electronic sensitivities of pristine, Al- and Si-doped BC3 nanosheets to the EB molecule were investigated in this study using density functional theory. It is found that the pure BC3 was ineffective in sensing EB due to low adsorption energy and sensitivity. Aluminum- and silicon-doped BC3 nanosheets were effective in forming a strong interaction with EB and were also sensitive. Our calculations show that the band gaps of the Al-doped and Si-doped BC3 sheets were significantly decreased upon EB adsorption, which increased the electrical conductance of the sheets and the sensitivity. However, Si-doped BC3 had a recovery time of almost 22 hours, making it less potent than Al-doped BC3, which had a recovery time of just 7.7 minutes. The shorter recovery time of the Al-doped BC3 sheet is due to its moderate adsorption energy of 25.8 kcal mol-1. These results can help facilitate the development of an EB biosensor for COVID-19 testing and other similar applications.

Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome through Modulation of Microbiome in the Gut-Lung Axis.

Acute respiratory distress syndrome (ARDS) is a serious lung condition characterized by severe hypoxemia leading to limitations of oxygen needed for lung function. In this study, we investigated the effect of anandamide (AEA), an endogenous cannabinoid, on Staphylococcal enterotoxin B (SEB)-mediated ARDS in female mice. Single-cell RNA sequencing data showed that the lung epithelial cells from AEA-treated mice showed increased levels of antimicrobial peptides (AMPs) and tight junction proteins. MiSeq sequencing data on 16S RNA and LEfSe analysis demonstrated that SEB caused significant alterations in the microbiota, with increases in pathogenic bacteria in both the lungs and the gut, while treatment with AEA reversed this effect and induced beneficial bacteria. AEA treatment suppressed inflammation both in the lungs as well as gut-associated mesenteric lymph nodes (MLNs). AEA triggered several bacterial species that produced increased levels of short-chain fatty acids (SCFAs), including butyrate. Furthermore, administration of butyrate alone could attenuate SEB-mediated ARDS. Taken together, our data indicate that AEA treatment attenuates SEB-mediated ARDS by suppressing inflammation and preventing dysbiosis, both in the lungs and the gut, through the induction of AMPs, tight junction proteins, and SCFAs that stabilize the gut-lung microbial axis driving immune homeostasis.