IntroductionA novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in China and affected millions of people around the world with a very high mortality rate (Y.C. Zhu et al., 2020), much more than the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) combined (Mahase, 2020). The disease, with the symptoms of fever and dry cough, caused by the current coronavirus was named as COVID-19 by WHO and declared as pandemic due to the ongoing global health crisis which SARS-CoV-2 led to (World Health Organization, 2020;Zhu et al., 2020). Several coronavirus species have been identified that cause human diseases including SARS-CoV, MERS-CoV, and the current coronavirus, SARS-CoV-2. Human coronaviruses mostly have a long single-stranded RNA with positive polarity (Hilgenfeld and Peiris, 2013). SARS-CoV-2 virions have a double layer lipid envelope structure on the outer surface with various proteins such as spike (S) protein, envelope (E) protein, and membrane (M) protein embedded in (X. Li et al., 2020). Phylogenetic analysis of complete genome sequences of SARS-CoV-2 revealed that the new virus shares 89.1% nucleotide sequence identity with SARS-like coronaviruses detected in bats. SARS-CoV-2 is closely related to SARS-CoV but more distant to MERS (Elfiky, 2020; A. F. Wu et al., 2020). SARS-CoV-2 RNA dependent RNA polymerase, which has been used as target for antiviral inhibitors, shares 90.1% sequence identity to SARS-CoV but 56.7% that of to MERS-CoV (Elfiky, 2020). While MERS-CoV uses dipeptidyl peptidase 4 (DPP4), SARS-CoV and SARS-CoV-2 use the angiotensin-converting enzyme 2 (ACE2) to enter human cells. It has been shown that receptor affinity of SARS-CoV-2 to ACE2 is higher than the strain of SARS-CoV in (Wan et al., 2020. Although the SARS-CoV-2 has spread more quickly compared to SARS-CoV and MERS-CoV due to possible increased globalization, they do not seem very different regarding their course of disease and there are several similarities Abstract: COVID-19, a novel infectious disease, caused by SARS-CoV-2, affected millions of people around the world with a high mortality rate. Although SARS-CoV-2 mainly causes lung infection, gastrointestinal symptoms described in COVID-19 patients and detection of the viral RNA in feces of infected patients drove attentions to a possible fecal-oral transmission route of SARS-CoV-2. However, not only the viral RNA but also the infectious viral particles are required for the viral infection and no proof has been demonstrated the transmission of the infectious virus particles via the fecal-oral route yet. Growing evidence indicates the crosstalk between gut microbiota and lung, that maintains host homeostasis and disease development with the association of immune system. This gut-lung interaction may influence the COVID-19 severity in patients with extrapulmonary conditions. Severity of COVID-19 has mostly associated with old ages and underlying medical conditions...

Glycomacropeptide (GMP) is a 64-amino acid (AA) glycophosphopeptide with application to the nutritional management of phenylketonuria (PKU), obesity, and inflammatory bowel disease (IBD). GMP is a putative prebiotic based on extensive glycosylation with sialic acid, galactose, and galactosamine. Our objective was to determine the prebiotic properties of GMP by characterizing cecal and fecal microbiota populations, short-chain fatty acids (SCFA), and immune responses. Weanling PKU (Pah(enu2)) and wild-type (WT) C57Bl/6 mice were fed isoenergetic AA, GMP, or casein diets for 8 wk. The cecal content and feces were collected for microbial DNA extraction to perform 16S microbiota analysis by Ion Torrent PGM sequencing. SCFA were determined by gas chromatography, plasma cytokines via a Bio-Plex Pro assay, and splenocyte T cell populations by flow cytometry. Changes in cecal and fecal microbiota are primarily diet dependent. The GMP diet resulted in a reduction from 30-35 to 7% in Proteobacteria, genera Desulfovibrio, in both WT and PKU mice with genotype-dependent changes in Bacteroidetes or Firmicutes. Cecal concentrations of the SCFA acetate, propionate, and butyrate were increased with GMP. The percentage of stimulated spleen cells producing interferon-γ (IFN-γ) was significantly reduced in mice fed GMP compared with casein. In summary, plasma concentrations of IFN-γ, TNF-α, IL-1β, and IL-2 were reduced in mice fed GMP. GMP is a prebiotic based on reduction in Desulfovibrio, increased SCFA, and lower indexes of inflammation compared with casein and AA diets in mice. Functional foods made with GMP may be beneficial in the management of PKU, obesity, and IBD.

Colon cancer is one of the most common cancer around the world. Exopolysaccharides (EPSs) produced by lactobacilli as potential prebiotics have been found to have an anti-tumor effect. In this study, lyophilized EPSs of four Lactobacillus spp. for their impact on apoptosis in colon cancer cells (HT-29) was evaluated using flow cytometry. The relationship between capability of a lactobacilli-EPS to induce apoptosis and their monosaccharide composition, molecular weight (MW), and linkage type was investigated by HPLC, SEC, and NMR, respectively. Changes in apoptotic-markers were examined by qPCR and Western Blotting. EPSs were capable of inhibiting proliferation in a time-dependent manner and induced apoptosis via increasing the expression of Bax, Caspase 3 and 9 while decreasing Bcl-2 and Survivin. All EPSs contained mannose, glucose, and N-acetylglucosamine with different relative proportions. Some contained arabinose or fructose. MW ranged from 10 2 –10 4 Da with two or three fractions. EPS of L. delbrueckii ssp. bulgaricus B3 having the highest amount of mannose and the lowest amount of glucose, showed the highest apoptosis induction. In conclusion, lactobacilli-EPSs inhibit cell proliferation in HT-29 via apoptosis. Results suggest that a relationship exists between the ability of EPS to induce apoptosis and its mannose and glucose composition.

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Lactobacilli have been associated with a variety of immunomodulatory effects and some of these effects have been related to changes in gastrointestinal microbiota. However, the relationship between probiotic dose, time since probiotic consumption, changes in the microbiota, and immune system requires further investigation. The objective of this study was to determine if the effect of Lactobacillus casei 32G on the murine gastrointestinal microbiota and immune function are dose and time dependent. Mice were fed L. casei 32G at doses of 106, 107, or 108 CFU/day/mouse for seven days and were sacrificed 0.5h, 3.5h, 12h, or 24h after the last administration. The ileum tissue and the cecal content were collected for immune profiling by qPCR and microbiota analysis, respectively. The time required for L. casei 32G to reach the cecum was monitored by qPCR and the 32G bolus reaches the cecum 3.5h after the last administration. L. casei 32G altered the cecal microbiota with the predominance of Lachnospiraceae IS, and Oscillospira decreasing significantly (p < 0.05) in the mice receiving 108 CFU/mouse 32G relative to the control mice, while a significant (p < 0.05) increase was observed in the prevalence of lactobacilli. The lactobacilli that increased were determined to be a commensal lactobacilli. Interestingly, no significant difference in the overall microbiota composition, regardless of 32G doses, was observed at the 12h time point. A likely explanation for this observation is the level of feed derived-nutrients resulting from the 12h light/dark cycle. 32G results in consistent increases in Clec2h expression and reductions in TLR-2, alpha-defensins, and lysozyme. Changes in expression of these components of the innate immune system are one possible explanation for the observed changes in the cecal microbiota. Additionally, 32G administration was observed to alter the expression of cytokines (IL-10rb and TNF-α) in a manner consistent with an anti-inflammatory response.