Progress in understanding the health promoting effect of egg yolk immunoglobulin

As an important immuneoactive component in eggs, yolk immunoglobulin (IgY) shows great competitiveness in research and production due to its good stability, high safety, low cost, easy availability, strong immune activity, and no drug resistance. This article highlights the significant advantages of IgY as a good antibiotic substitute in the prevention and treatment of viral and bacterial diseases. Also, IgY has great potential in the regulation of nutrient metabolism balance, intestinal microflora and immune homeostasis by affecting key rate-limiting enzymes, and relevant receptors and inflammatory factors specifically. Proper diet and targeted delivery of foodborne IgY may be a new perspective on inflammation regulation, disease control, nutritional balance or homeostasis, and oral microencapsulated IgY is expected to be a new approach against increasing public health emergencies (such as COVID-19 pandemic).

Nutrition Strategies Pre-infection, during, and Post-infection with Coronavirus Disease

Coronavirus disease is a serious viral infection that is characterized by severe inflammation and lymphopenia. The virus attacks many organs causing acute respiratory distress and malfunctioning of the organs leading to death. Through strengthening of the innate immune system, a balanced diet plays a critical role in defense against bacterial and viral diseases. A healthy diet before, during and after an infection can lessen the severity of the symptoms and speed up the recovery of damaged cells. Due to the Mediterranean diet's high concentration of bioactive polyphenols, which have antioxidant, anti-inflammatory, and antithrombic properties, numerous studies have suggested that it is a preventative dietary strategy against many diseases including coronavirus disease. Nutrition and herbal plants play a key role to enhance the immunity of people to protect and fight against coronavirus. Diet rich in antioxidants and phytochemicals represents perfect barrier to the virus through elevation of the innate immunity of the body. In addition, gut microbiota including prebiotics, probiotics, and synbiotics were found to enhance immunity to reduce the symptoms of the disease during infection. Protein-rich foods and honey bee products reported significant role during and post-coronavirus infection. This review presents updated information from original pre-clinical and clinical researches, and review articles as well to expose the nutritive strategies including breastfeeding benefits to infants pre-infection, during, and post-infection with coronavirus.Copyright © 2023, Scientific Foundation SPIROSKI. All rights reserved.

Gut Microbiota in Coronavirus Disease 2019

Coronavirus disease 2019 (COVID-19) pandemic has changed the globe ever since its first appearance in December 2019. It is an acute respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and over 540 million people have contracted COVID-19 as of mid-2022. For COVID-19 patients, gastrointestinal symptoms including anorexia and diarrhoea are frequently occurred, implicating the involvement of gut microbiota in the pathogenesis of COVID-19. Indeed, accumulating evidence has reported the association of altered microbiota with SARS-CoV-2 infection, disease severity, and post-acute COVID-19 syndrome. In this chapter, the roles of gut microbiota in COVID-19 as well as its mechanistic interplays with host after SARS-CoV-2 infection are explored. Given its importance to this disease, approaches to restore the altered microbiota may be utilised as potential treatments of COVID-19. Hence, different strategies to modulate the microbiota including dietary intervention, prebiotics, and probiotics against SARS-CoV-2 infection are also discussed. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.

How Toll-like receptors influence Parkinson's disease in the microbiome-gut-brain axis.

Recently, a large number of experimenters have found that the pathogenesis of Parkinson's disease may be related to the gut microbiome and proposed the microbiome-gut-brain axis. Studies have shown that Toll-like receptors, especially Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4), are key mediators of gut homeostasis. In addition to their established role in innate immunity throughout the body, research is increasingly showing that the Toll-like receptor 2 and Toll-like receptor 4 signaling pathways shape the development and function of the gut and enteric nervous system. Notably, Toll-like receptor 2 and Toll-like receptor 4 are dysregulated in Parkinson's disease patients and may therefore be identified as the core of early gut dysfunction in Parkinson's disease. To better understand the contribution of Toll-like receptor 2 and Toll-like receptor 4 dysfunction in the gut to early α-synuclein aggregation, we discussed the structural function of Toll-like receptor 2 and Toll-like receptor 4 and signal transduction of Toll-like receptor 2 and Toll-like receptor 4 in Parkinson's disease by reviewing clinical, animal models, and in vitro studies. We also present a conceptual model of the pathogenesis of Parkinson's disease, in which microbial dysbiosis alters the gut barrier as well as the Toll-like receptor 2 and Toll-like receptor 4 signaling pathways, ultimately leading to a positive feedback loop for chronic gut dysfunction, promoting α-synuclein aggregation in the gut and vagus nerve.

Revitalizing myocarditis treatment through gut microbiota modulation: unveiling a promising therapeutic avenue.

Numerous studies have demonstrated that gut microbiota plays an important role in the development and treatment of different cardiovascular diseases, including hypertension, heart failure, myocardial infarction, arrhythmia, and atherosclerosis. Furthermore, evidence from recent studies has shown that gut microbiota contributes to the development of myocarditis. Myocarditis is an inflammatory disease that often results in myocardial damage. Myocarditis is a common cause of sudden cardiac death in young adults. The incidence of myocarditis and its associated dilated cardiomyopathy has been increasing yearly. Myocarditis has gained significant attention on social media due to its association with both COVID-19 and COVID-19 vaccinations. However, the current therapeutic options for myocarditis are limited. In addition, little is known about the potential therapeutic targets of myocarditis. In this study, we review (1) the evidence on the gut-heart axis, (2) the crosslink between gut microbiota and the immune system, (3) the association between myocarditis and the immune system, (4) the impact of gut microbiota and its metabolites on myocarditis, (5) current strategies for modulating gut microbiota, (6) challenges and future directions for targeted gut microbiota in the treatment of myocarditis. The approach of targeting the gut microbiota in myocarditis is still in its infancy, and this is the study to explore the gut microbiota-immune system-myocarditis axis. Our findings are expected to pave the way for the use of gut microbiota as a potential therapeutic target in the treatment of myocarditis.

Enteric nervous system as a target and source of SARS-CoV-2 and other viral infections.

Coronavirus disease 2019 (COVID-19) has been demonstrated to affect several systems of the human body, including the gastrointestinal and nervous systems. The enteric nervous system (ENS) is a division of the autonomic nervous system that extends throughout the gut, regulates gastrointestinal function, and is therefore involved in most gut dysfunctions, including those resulting from many viral infections. Growing evidence highlights enteric neural cells and microbiota as important players in gut inflammation and dysfunction. Furthermore, the ENS and gastrointestinal immune system work together establishing relevant neuroimmune interactions during both health and disease. In recent years, gut-driven processes have also been implicated as players in systemic inflammation and in the initiation and propagation of several central nervous system pathologies, which seem to be hallmarks of COVID-19. In this review, we aim to describe evidence of the gastrointestinal and ENS infection with a focus on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We discuss here viral-induced mechanisms, neuroplasticity, and neuroinflammation to call attention to the enteric neuroglial network as a nervous system with a sensitive and crucial position to be not only a target of the new coronavirus but also a way in and trigger of COVID-19-related symptoms.

Mild SARS-CoV-2 infection results in long-lasting microbiota instability.

Viruses targeting mammalian cells can indirectly alter the gut microbiota, potentially compounding their phenotypic effects. Multiple studies have observed a disrupted gut microbiota in severe cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that require hospitalization. Yet, despite demographic shifts in disease severity resulting in a large and continuing burden of non-hospitalized infections, we still know very little about the impact of mild SARS-CoV-2 infection on the gut microbiota in the outpatient setting. To address this knowledge gap, we longitudinally sampled 14 SARS-CoV-2-positive subjects who remained outpatient and 4 household controls. SARS-CoV-2 cases exhibited a significantly less stable gut microbiota relative to controls. These results were confirmed and extended in the K18-humanized angiotensin-converting enzyme 2 mouse model, which is susceptible to SARS-CoV-2 infection. All of the tested SARS-CoV-2 variants significantly disrupted the mouse gut microbiota, including USA-WA1/2020 (the original variant detected in the USA), Delta, and Omicron. Surprisingly, despite the fact that the Omicron variant caused the least severe symptoms in mice, it destabilized the gut microbiota and led to a significant depletion in Akkermansia muciniphila. Furthermore, exposure of wild-type C57BL/6J mice to SARS-CoV-2 disrupted the gut microbiota in the absence of severe lung pathology.IMPORTANCETaken together, our results demonstrate that even mild cases of SARS-CoV-2 can disrupt gut microbial ecology. Our findings in non-hospitalized individuals are consistent with studies of hospitalized patients, in that reproducible shifts in gut microbial taxonomic abundance in response to SARS-CoV-2 have been difficult to identify. Instead, we report a long-lasting instability in the gut microbiota. Surprisingly, our mouse experiments revealed an impact of the Omicron variant, despite producing the least severe symptoms in genetically susceptible mice, suggesting that despite the continued evolution of SARS-CoV-2, it has retained its ability to perturb the intestinal mucosa. These results will hopefully renew efforts to study the mechanisms through which Omicron and future SARS-CoV-2 variants alter gastrointestinal physiology, while also considering the potentially broad consequences of SARS-CoV-2-induced microbiota instability for host health and disease.

Probiotics improve symptoms of patients with COVID-19 through gut-lung axis: a systematic review and meta-analysis.

Background: Multi system symptoms such as gastrointestinal tract and respiratory tract exist in coronavirus disease 2019 (COVID-19) patients. There is a lack of reliable evidence to prove that probiotics are effective in improving these symptoms. In this study, we aimed to evaluate the efficacy of probiotics in meta-analysis. Methods: We systematically searched PubMed, Embase, Web of Science, and Cochrane Library up to February 15, 2023. Randomized controlled trials or high quality retrospective studies comparing the efficacy of probiotics as supplementation with non-probiotics in improving symptoms for patients with COVID-19 were included. This meta-analysis assessed endpoints using Review Manager 5.3. Result: Ten citations comprising 1198 patients with COVID-19 were included. The results showed that probiotics could increase the number of people with overall symptom improvement (RR = 1.62, 95% CI [1.10, 2.38], P = 0.01) and shorten the duration (days) of overall symptoms (MD = -1.26, 95% CI [-2.36, -0.16], P = 0.02). For the duration (days) of specific symptoms, probiotics could improve diarrhea (MD = -2.12, 95% CI [-2.41, -1.83], P < 0.00001), cough (MD = -2.21, 95% CI [-4.56, 0.13], P = 0.06) and shortness of breath (MD = -1.37, 95% CI [-2.22, -0.53], P = 0.001). Probiotics had no obvious effect on fever, headache and weakness. For inflammation, probiotics could effectively reduce C-reactive Protein (CRP) serum level (mg/L) (MD = -4.03, 95% CI [-5.12, -2.93], P < 0.00001). Regarding hospital stay (days), probiotics group was shorter than non-probiotics group (MD = -0.98, 95% CI [-1.95, -0.01], P = 0.05). Conclusion: To some extent probiotics could improve the overall symptoms, inflammatory reaction and shorten hospital stay of patients with COVID-19. Probiotics may improve gastrointestinal symptoms (such as improving intestinal flora and reducing the duration of diarrhea) and further improve respiratory symptoms through the gut-lung axis. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=398309, identifier: CRD42023398309.

Deducing the Interplay Between Gut Flora and Respiratory Diseases: A New Therapeutic Strategy?

The gastrointestinal system, also referred to as the gut, is a universe that colonizes trillions of microbes. In addition to its digestive functions, the gut represents a biosystem that determines all the health vectors. It is now recognized as one of the body's defense systems, and good gut health regulates the body's immune responses. Disturbance of this barrier can trigger many diseases, including respiratory tract infections, as there is a close correlation between the gut microbiome and the chances of triggering illness. This review investigates the various factors affecting the gut microbiome, the diseases that can result from the dysregulation of the same, and their molecular mechanisms. The most basic solution to tackle this problem is to maintain the gut microbiome at the desired level. Timely diagnosis and interventions are needed for the proper management of the ensuing conditions. It is important to address the effects of factors on the gut microbiome and thereby regulate this level. The study also found that dysregulation in the system can lead to various diseases such as asthma, COPD, lung cancer following their respective pathways. In short, this paper reinforces the importance of the gut microbiome, the need to maintain its average level, and the need for proper interventions to treat the consequences. The manuscript posit that medications, diet as well and good physiological conditions of the human body can alter the microbiome and can ward off respiratory infections.

Dynamic associations between the respiratory tract and gut antibiotic resistome of patients with COVID-19 and its prediction power for disease severity.

The antibiotic resistome is the collection of all antibiotic resistance genes (ARGs) present in an individual. Whether an individual's susceptibility to infection and the eventual severity of coronavirus disease 2019 (COVID-19) is influenced by their respiratory tract antibiotic resistome is unknown. Additionally, whether a relationship exists between the respiratory tract and gut ARGs composition has not been fully explored. We recruited 66 patients with COVID-19 at three disease stages (admission, progression, and recovery) and conducted a metagenome sequencing analysis of 143 sputum and 97 fecal samples obtained from them. Respiratory tract, gut metagenomes, and peripheral blood mononuclear cell (PBMC) transcriptomes are analyzed to compare the gut and respiratory tract ARGs of intensive care unit (ICU) and non-ICU (nICU) patients and determine relationships between ARGs and immune response. Among the respiratory tract ARGs, we found that Aminoglycoside, Multidrug, and Vancomycin are increased in ICU patients compared with nICU patients. In the gut, we found that Multidrug, Vancomycin, and Fosmidomycin were increased in ICU patients. We discovered that the relative abundances of Multidrug were significantly correlated with clinical indices, and there was a significantly positive correlation between ARGs and microbiota in the respiratory tract and gut. We found that immune-related pathways in PBMC were enhanced, and they were correlated with Multidrug, Vancomycin, and Tetracycline ARGs. Based on the ARG types, we built a respiratory tract-gut ARG combined random-forest classifier to distinguish ICU COVID-19 patients from nICU patients with an AUC of 0.969. Cumulatively, our findings provide some of the first insights into the dynamic alterations of respiratory tract and gut antibiotic resistome in the progression of COVID-19 and disease severity. They also provide a better understanding of how this disease affects different cohorts of patients. As such, these findings should contribute to better diagnosis and treatment scenarios.

BBIBP-CorV Vaccination against the SARS-CoV-2 Virus Affects the Gut Microbiome.

Several observational studies have confirmed that the severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) might substantially affect the gastrointestinal (GI) system by replicating in human small intestine enterocytes. Yet, so far, no study has reported the effects of inactivated SARS-CoV-2 virus vaccines on gut microbiota alterations. In this study, we examined the effects of the BBIBP-CorV vaccine (ChiCTR2000032459, sponsored by the Beijing Institute of Biological Products/Sinopharm), on gut microbiota. Fecal samples were collected from individuals whoreceived two doses of intramuscular injection of BBIBP-CorV and matched unvaccinated controls. DNA extracted from fecal samples was subjected to 16S ribosomal RNA sequencing analysis. The composition and biological functions of the microbiota between vaccinated and unvaccinated individuals were compared. Compared with unvaccinated controls, vaccinated subjects exhibited significantly reduced bacterial diversity, elevated firmicutes/bacteroidetes (F/B) ratios, a tendency towards Faecalibacterium-predominant enterotypes, and altered gut microbial compositions and functional potentials. Specifically, the intestinal microbiota in vaccine recipients was enriched with Faecalibacterium and Mollicutes and with a lower abundance of Prevotella, Enterococcus, Leuconostocaceae, and Weissella. Microbial function prediction by phylogenetic investigation of communities using reconstruction of unobserved states (PICRUSt) analysis further indicated that Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in carbohydrate metabolism and transcription were positively associated with vaccine inoculation, whereas capacities in neurodegenerative diseases, cardiovascular diseases, and cancers were negatively affected by vaccines. Vaccine inoculation was particularly associated with gut microbiota alterations, as was demonstrated by the improved composition and functional capacities of gut microbiota.

Hyaluronan with Different Molecular Weights Can Affect the Gut Microbiota and Pathogenetic Progression of Post-Intensive Care Syndrome Mice in Different Ways.

Post-intensive care syndrome (PICS) poses a serious threat to the health of intensive care unit (ICU) survivors, and effective treatment options are currently lacking. With increasing survival rates of ICU patients worldwide, there is a rising interest in developing methods to alleviate PICS symptoms. This study aimed to explore the potential of using Hyaluronan (HA) with different molecular weights as potential drugs for treating PICS in mice. Cecal ligation and puncture (CLP) were used to establish a PICS mice model, and high molecular weight HA (HMW-HA) or oligo-HA were used as therapeutic agents. Pathological and physiological changes of PICS mice in each group were monitored. 16S rRNA sequencing was performed to dissect gut microbiota discrepancies. The results showed that both molecular weights of HA could increase the survival rate of PICS mice at the experimental endpoint. Specifically, 1600 kDa-HA can alleviate PICS in a short time. In contrast, 3 kDa-HA treatment decreased PICS model survivability in the early stages of the experiment. Further, via 16S rRNA sequence analysis, we observed the changes in the gut microbiota in PICS mice, thereby impairing intestinal structure and increasing inflammation. Additionally, both types of HA can reverse this change. Moreover, compared to 1600 kDa-HA, 3 kDa-HA can significantly elevate the proportion of probiotics and reduce the abundance of pathogenic bacteria (Desulfovibrionaceae and Enterobacteriaceae). In conclusion, HA holds the advantage of being a potential therapeutic drug for PICS, but different molecular weights can lead to varying effects. Moreover, 1600 kDa-HA showed promise as a protective agent in PICS mice, and caution should be taken to its timing when considering using 3 kDa-HA.

Functional Foods: A Promising Strategy for Restoring Gut Microbiota Diversity Impacted by SARS-CoV-2 Variants.

Natural herbs and functional foods contain bioactive molecules capable of augmenting the immune system and mediating anti-viral functions. Functional foods, such as prebiotics, probiotics, and dietary fibers, have been shown to have positive effects on gut microbiota diversity and immune function. The use of functional foods has been linked to enhanced immunity, regeneration, improved cognitive function, maintenance of gut microbiota, and significant improvement in overall health. The gut microbiota plays a critical role in maintaining overall health and immune function, and disruptions to its balance have been linked to various health problems. SARS-CoV-2 infection has been shown to affect gut microbiota diversity, and the emergence of variants poses new challenges to combat the virus. SARS-CoV-2 recognizes and infects human cells through ACE2 receptors prevalent in lung and gut epithelial cells. Humans are prone to SARS-CoV-2 infection because their respiratory and gastrointestinal tracts are rich in microbial diversity and contain high levels of ACE2 and TMPRSS2. This review article explores the potential use of functional foods in mitigating the impact of SARS-CoV-2 variants on gut microbiota diversity, and the potential use of functional foods as a strategy to combat these effects.

Advancements in organs-on-chips technology for viral disease and anti-viral research

Disease models that can accurately recapitulate human pathophysiology during infection and clinical response to antiviral therapeutics are still lacking, which represents a major barrier in drug development. The emergence of human Organs-on-a-Chip that integrated microfluidics with three-dimensional (3D) cell culture, may become the potential solution for this urgent need. Human Organs-on-a-Chip aims to recapitulate human pathophysiology by incorporating tissue-relevant cell types and their microenvironment, such as dynamic fluid flow, mechanical cues, tissue–tissue interfaces, and immune cells to increase the predictive validity of in vitro experimental models. Human Organs-on-a-Chip has a broad range of potential applications in basic biomedical research, preclinical drug development, and personalized medicine. This review focuses on its use in the fields of virology and infectious diseases. We reviewed various types of human Organs-on-a-Chip-based viral infection models and their application in studying viral life cycle, pathogenesis, virus-host interaction, and drug responses to virus- and host-targeted therapies. We conclude by proposing challenges and future research avenues for leveraging this promising technology to prepare for future pandemics.

Increase in gut permeability and oxidized ldl is associated with post-acute sequelae of SARS-CoV-2.

Background: Post-acute sequelae of SARS-CoV-2 (PASC) is marked by persistent or newly developing symptoms beyond 4 weeks of infection. Investigating gut integrity, oxidized lipids and inflammatory markers is important for understanding PASC pathogenesis. Methods: A cross-sectional study including COVID+ with PASC, COVID+ without PASC, and COVID-negative (COVID-) participants. We measured plasma markers by enzyme-linked immunosorbent assay to assess intestinal permeability (ZONULIN), microbial translocation (lipopolysaccharide-binding protein or LBP), systemic inflammation (high-sensitivity C-reactive protein or hs-CRP), and oxidized low-density lipoprotein (Ox-LDL). Results: 415 participants were enrolled in this study; 37.83% (n=157) had prior COVID diagnosis and among COVID+, 54% (n=85) had PASC. The median zonulin among COVID- was 3.37 (IQR: 2.13, 4.91) mg/mL, 3.43 (IQR: 1.65, 5.25) mg/mL among COVID+ no PASC, and highest [4.76 (IQR: 3.2, 7.35) mg/mL] among COVID+ PASC+ (p<.0001). The median ox-LDL among COVID- was 47.02 (IQR: 35.52, 62.77) U/L, 57.24 (IQR: 40.7, 75.37) U/L among COVID+ No PASC, and the highest [76.75 (IQR: 59.95, 103.28) U/L] among COVID+ PASC+ (p<.0001). COVID+ PASC+ was positively associated with zonulin (p=0.0002) and ox-LDL (p<.0001), and COVID- was negatively associated with ox-LDL (p=0.01), compared to COVID+ No PASC. Every unit increase in zonulin was associated with 44% higher predicted odds of having PASC [aOR: 1.44 (95%CI: 1.1, 1.9)] and every one-unit increase in ox-LDL was associated with more than four-fold increased odds of having PASC [aOR: 2.44 (95%CI: 1.67, 3.55)]. Conclusions: PASC is associated with increased gut permeability and oxidized lipids. Further studies are needed to clarify whether these relationships are causal which could lead to targeted therapeutics.

Bifidobacterium: a probiotic for the prevention and treatment of depression.

Depression is a common psychological disease, which has become one of the main factors affecting human health. It has a serious impact on individuals, families, and society. With the prevalence of COVID-19, the incidence of depression has further increased worldwide. It has been confirmed that probiotics play a role in preventing and treating depression. Especially, Bifidobacterium is the most widely used probiotic and has positive effects on the treatment of depression. The mechanisms underlying its antidepressant effects might include anti-inflammation and regulation of tryptophan metabolism, 5-hydroxytryptamine synthesis, and the hypothalamus-pituitary-adrenal axis. In this mini-review, the relationship between Bifidobacterium and depression was summarized. It is hoped that Bifidobacterium-related preparations would play a positive role in the prevention and treatment of depression in the future.

Intestinal microbiota, pain, dementia

The review is dedicated the interconnection between neurodegenerative diseases, chronic pain and gut microbiota's structure and function. The gut microbiota's role in gut-brain axis, neuroimmune interaction is considered. The modern data about gut dysbiosis in Alzheimer disease, Parkinson disease, osteoarthrosis, neuropathic pain in COVID infection, muscular-skeletal pain in fibromyalgia, irritable bowel syndrome et cetera are provided. The gut microbiota's modification by means of pre and probiotics in combination with medicines and diet modification can be used for the treatment of chronic pain and dementia.Copyright © T.M. MANEVICH.

Delineating Health and Health System: Mechanistic Insights into Covid 19 Complications

This book discusses the organ-specific systemic manifestations of COVID-19. The initial chapters of the book review the origin and evolution of the coronaviruses, followed by pathogenesis and immune response during COVID-19 infection. The book also provides insight into the role of angiotensin-converting enzyme 2 in the onset of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis. It summarizes the neurological aspects of SARS-CoV2, including transmission pathways, mechanisms of invasion into the nervous system, and mechanisms of neurological disease. It also delineates the association of severe disease with high blood plasma levels of inflammatory cytokines and inflammatory markers in SARS-CoV-2 infection. Lastly, it discusses the perturbation of gut microbiota by SARS-CoV-2 and uncovers the potential risk of virus infection on reproductive health. © The Editor(s) (if applicable) and The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2021.