Gastrointestinal symptoms and disorders related to COVID-19. Lessons learned from gastroenterologists

COVID-19 is mainly a respiratory illness caused by the SARS-CoV-2 but can also lead to GI symptoms. The primary host receptor which mediates the mechanism as SARS-CoV-2 enters the cell is the ACE2 receptor. Therefore, GI symptoms can be common in COVID-19, and in some cases, they are the first manifestation even before fever and respiratory symptoms. In addition, the liver function tests alteration often is related to a worse prognosis. The exact incidence of GI symptoms is a matter of debate. Moreover, wide variation concerning GI symptoms frequency exists, but the predominant ones seem to be diarrhea, anorexia, nausea, vomiting, and abdominal pain or discomfort.This review summarizes the most relevant findings of COVID-19 on the digestive system, including the liver, biliary tract, pancreas, the most common GI symptoms, and the atypical clinical GI manifestations.Copyright © 2022 Sociedad Medica del Hospital General de Mexico. Published by Permanyer.

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.

A systematic review of gut microbiota profile in COVID-19 patients and among those who have recovered from COVID-19.

OBJECTIVES: Given the scale and persistence of coronavirus disease 2019 (COVID-19), significant attention has been devoted to understanding the relationship between human gut microbiota and COVID-19. In this systematic review we aimed to comprehensively assess the gut microbiota composition in patients infected with COVID-19 and those recovered from COVID-19 in comparison to healthy controls (HCs). METHODS: Peer-reviewed articles and preprints published up to September 1, 2022, were searched in Ovid MEDLINE, Ovid EMBASE, and SCOPUS. Observational studies reporting the gut microbiota profile in adult (≥18 years) COVID-19 patients or those recovered from COVID-19 compared to HCs were eligible for inclusion in this systematic review. The quality assessment of studies was performed using the Newcastle-Ottawa scale. RESULTS: We identified 27 studies comprising 18 studies that compared COVID-19 patients and six that compared recovered COVID-19 patients to HCs, while the other three studies compared both COVID-19 and recovered COVID-19 patients to HCs. Compared to HCs, decreased gut microbial diversity and richness and a distinctive microbial composition were reported in COVID-19 patients and recovered COVID-19 patients. In COVID-19 patients, Bacteroidetes were found to be enriched, and Firmicutes depleted. Decreased short-chain fatty acid (SCFA)-producing bacteria, such as Faecalibacterium, Ruminococcus, and Bifidobacterium, among others, were also observed in COVID-19 patients, which were not restored to normal levels in those who recovered. CONCLUSION: Gut dysbiosis was evident in COVID-19, and available data suggested that dysbiosis persisted even in recovered COVID-19 patients, with decreased Firmicutes and SCFA-producing bacteria.

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.

Loss of Bifidobacteria in Lyme Disease: Cause or Effect

Introduction: Lyme disease is a poorly understood condition which starts with a rash but may continue with chronic fatigue and neurological symptoms. Approximately 1 in 5 early Lyme disease patients have GI symptoms, such as nausea, anorexia, abdominal pain, or diarrhea. Lyme disease is thought to be cased by microbes in the spirochetes phylum transmitted by black legged ticks. Lyme-related healthcare costs in America exceed 1.3 billion dollars annually. Bifidobacteria are known for their beneficial probiotic actions within the human gut microbiome. Their numbers are reduced in severe COVID-19, Clostridioides difficile infection and Inflammatory Bowel Disease. To our knowledge Bifidobacteria levels have not been studied in Lyme disease patients. Given the importance of Bifidobacterium abundance in other diseases, we focused on relative abundance of Bifidobacterium in fecal samples of patients with Lyme disease compared to controls. Method(s): Fecal samples were assessed for relative abundance of Bifidobacterium in Healthy Control subjects without Lyme disease (n=20) compared to patients with Lyme disease (n=39). The average symptom duration in patients with Lyme disease was 5 years and none were on antibiotics 2 weeks prior to sample collection (range of symptoms from 1 month to 20 years, all treated initially with antibiotics).Metagenomics Next Generation sequencing was performed on fecal samples, where DNA samples were extracted and normalized for library downstream analysis using Shotgun Methodology. Mann- Whitney Statistical test was used for comparison. This study was IRB approved. Result(s): Relative Abundance of bifidobacteria was significantly decreased (p< 0.0001) in patients with Lyme disease. Median and interquartile range (IQR) were: Control (Median:4.175%;IQR:1.72-10.27%) and Lyme disease (Median:0.0014%;IQR:0.00%-0.96%)(Figure). 30/39 Lyme disease patients (77%) were found to possess < 1% relative abundance of Bifidobacterium in their stool sample. Of interest only 1/39 samples showed presence of Spirochetes in stool samples. Conclusion(s): This is the first study that demonstrates low levels of Bifidobacteria in patients with chronic Lyme disease. These results raise three questions;whether the disease was caused by 1. the original microbe creating loss of Bifidobacterium 2. baseline low Bifidobacteria due likely to either diet or medications or 3. excessive treatment. Given Lyme disease comprises a gut dysbiosis issue, therapies should also aim at restoration of depleted Bifidobacteria. (Figure Presented).

[Intertwined long COVID theories to explain its etiopathogenesis]

This editorial lists the main current theories on long COVID, such as the theory of viral persistence and the one of immunothrombosis associated with deregulation of the immune system;it is discussed as well their interrelation, which finally explains the etiopathogenesis and physiopathology of this new syndrome that afflicts the survivors of COVID-19;it is also discussed the link between viral persistence with the formation of amyloid microthrombi based on the hypothesis that the spike protein causes amyloidogenesis, inducing organic chronic damage that will characterize long COVID. Copyright © 2023 Revista Medica del Instituto Mexicano del Seguro Social.

Gut Microbiome in COVID-19: New Insights

The last discovered organ of the human body is microbiome which is present at different sites in it. Gut microbiome consists of about 1000–1500 bacterial species and as regulated by genetic makeup, lifestyle, and environmental conditions, the gut microbiota of a healthy individual can comprise approximately 160 species of bacteria. Majority of gut microbiome consists of Firmicutes, Actinobacteria, Bacteroidetes, and to a lesser extent Proteobacteria, Euryarchaeota, Fusobacteria, and Verrucomicrobia. The gut-lung axis is involved in the migration of immune cells from gut to respiratory tract through circulation and encourages the host's ability to fight infections. The gut regulates the responses in lungs via host-acquired inflammatory mediators in the circulation. Dendritic cells located in the Peyer's patches of the intestine, macrophages, and Langerhans cells are the major antigen-presenting cells that play a vital role in the modulation and development of innate immune response. Gut microbiota interacts via the regulation and development of adaptive immune response. B and T lymphocytes are the key players of adaptive immunity. CD4 + T cells after activation differentiate into four major kinds of cell classes: (1) regulatory T cells (Treg), (2) Th2, (3) Th1, and (4) Th17 cells. Gut microbial interactions can induce the production of various types of immune cells as demonstrated by various studies. For instance, Clostridia induces the formation of Treg cells. Likewise, Bacteroides fragilis inhabiting the gut can incite the production of Th1 cells and production of T17 cells is stimulated by segmental filamentous bacteria. Gut microbiota also plays a vital role in the physiology and metabolism leading to the synthesis of various immunoregulatory metabolites such as SCFAs, antimicrobial peptides (AMPs), amino acids, and polyamines. SARS-CoV-2 virus entry to the cell is via ACE2 receptor present in respiratory epithelium and gut epithelium. This receptor is highly expressed (100 times more than in the lung) in the epithelial cells of the stomach, duodenum, ileum, and rectum as well as cholangiocytes and hepatocytes. High level of ACE2 receptor expressing in the gastrointestinal epithelial cells along with high-level co-expression of TMPRSS2 (cellular serine peptidase) causes coronavirus to infect gastrointestinal tract along with lungs leading to altered intestinal permeability and enterocyte malabsorption with symptoms of diarrhea in patients of COVID-19. Hence, COVID-19 patients with gastrointestinal symptoms have significantly longer duration of illness and viral clearance time than patients without any gastrointestinal symptoms. Obese patients with gut dysbiosis have decreased population of Bacteroides species. COVID-19 patients with type 2 diabetics have increased population of Fusobacterium, Ruminococcus, and Blautia with decreased population of Bacteroides, Bifidobacterium, Faecalibacterium, Akkermansia, and Roseburia. Diet with low fiber, high fat, and high carbohydrate causes gut dysbiosis. Intake of high-fiber diet consisting of whole grains, vegetables, and fruits induces growth of Bifidobacterium, Bacteroides, and Lactobacilli. Probiotics are nonpathogenic live organisms which are safe to be taken as dietary supplements. The major genera of probiotics are Lactobacillus, Bifidobacterium, and Saccharomyces. These probiotics increase the activity of T cells, NK cell, and polymorphonuclear cells. Prebiotics in the form of maize fiber, inulin, and polydextrose improves digestion and immunity. Hence, healthy gut microbiome with its strong immune intervention may bring recovery in COVID-19 patients. However, so far no published studies have reported that probiotics can be used as an adjunctive therapy in our fight against the SARS-CoV-2 infection. A far-reaching approach should consist of randomized, multicenter, controlled trials to explore the potential benefits of gut microbiome and how changes in dietary habits can be used as an add-on strategy against the COVID-19 pandemic. © The Author(s), under exc us ve licence to Springer Nature Singapore Pte Ltd. 2021.

Gut microbiota profile of COVID-19 patients: Prognosis and risk stratification (MicroCOVID-19 study).

Background: Gut microbiota is intrinsically associated with the immune system and can promote or suppress infectious diseases, especially viral infections. This study aims to characterize and compare the microbiota profile of infected patients with SARS-CoV-2 (milder or severe symptoms), non-infected people, and recovered patients. This is a national, transversal, observational, multicenter, and case-control study that analyzed the microbiota of COVID-19 patients with mild or severe symptoms at home, at the hospital, or in the intensive care unit, patients already recovered, and healthy volunteers cohabiting with COVID-19 patients. DNA was isolated from stool samples and sequenced in a NGS platform. A demographic questionnaire was also applied. Statistical analysis was performed in SPSS. Results: Firmicutes/Bacteroidetes ratios were found to be significantly lower in infected patients (1.61 and 2.57) compared to healthy volunteers (3.23) and recovered patients (3.89). Furthermore, the microbiota composition differed significantly between healthy volunteers, mild and severe COVID-19 patients, and recovered patients. Furthermore, Escherichia coli, Actinomyces naeslundii, and Dorea longicatena were shown to be more frequent in severe cases. The most common COVID-19 symptoms were linked to certain microbiome groups. Conclusion: We can conclude that microbiota composition is significantly affected by SARS-CoV-2 infection and may be used to predict COVID-19 clinical evolution. Therefore, it will be possible to better allocate healthcare resources and better tackle future pandemics.

Can the Therapeutic Spectrum of Probiotics be Extended: Exploring Potential of Gut Microbiome.

Natural therapeutic microorganisms provide a potent alternative healthcare treatment nowadays, with the potential to prevent several human diseases. These health-boosting living organisms, probiotics mostly belong to Gram-positive bacteria such as Lactobacillus, Bifidobacterium, Streptococcus, Saccharomyces, Bacillus and Enterococcus. Initiated almost a century ago, the probiotic application has come a long way. The present review is focused on the potential therapeutic role of probiotics in ameliorating multiple infections, such as upper respiratory tract infections and viral respiratory infections, including Covid-19; liver diseases and hepatic encephalopathy; neurological and psychiatric disorders; autoimmune diseases, particularly rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis. Apart from these, the therapeutic exacerbations of probiotics in urinary tract infections have been extremely promising, and several approaches are reviewed and presented here. We also present upcoming and new thrust areas where probiotic therapeutic interventions are showing promising results, like faecal microbial transplant and vaginal microbial transplant.

What We Know Now About Long Covid Syndromes?

It is now widely accepted that SARS-CoV-2 infection can affect long-term health and quality of life. Long COVID, a type of post-acute sequelae of SARS-CoV-2 infection (PASC) characterized by persistent unexplained symptoms, has a major impact on the health of many COVID-19 survivors. Although many individuals (up to 30%) experience some limited symptoms in the weeks and months following COVID-19, the prevalence of severe disabling Long COVID is less common (perhaps <5%). Long COVID syndromes are variable and include general (e.g., fatigue) and organ-system specific symptoms (e.g., shortness of breath, palpitations, neurocognitive symptoms), as well as symptoms resembling other medically unexplained syndromes (e.g., myalgic encephalomyelitis/chronic fatigue syndrome, dysautonomia, post-exertional malaise). For reasons not yet understood, female sex is a strong predictor of Long COVID, as is the presence of certain comorbidities, particularly obesity. Mechanisms that might plausibly contribute to Long COVID include irreversible tissue damage associated with acute infection, persistence of SARS-CoV-2 antigen or possibly a viral reservoir, residual or ongoing immune activation and inflammation, reactivation of other latent human viruses, microvascular dysregulation and thrombotic events, microbial translocation, dysbiosis, and autoimmune phenomena. These mechanisms may act in isolation or in combination to drive Long COVID syndromes. Notably, many if not all of these pathways have been implicated as possible mechanisms for the excess rate of cardiovascular disease and other comorbidities in people living with HIV. Industry engagement in Long COVID research is growing, and NIH funding for clinical trials is emerging through programs such as the RECOVER Initiative. As a result, we are entering an era of experimental medicine, in which potential interventions will be used as tools to probe the biology of the disease. This presentation will provide an overview of the proposed biological mechanisms contributing to Long COVID, with a focus on the current state of evidence, human and animal models, and the emerging therapeutic agenda.

Pbmc Immunophenotyping and Plasma Inflammatory Profile of Children with Long Covid

Background: Long COVID can be developed by individuals after an infection with SARS-CoV-2 as described by the WHO. Although this condition is more commonly described in adults, it can occur in children and adolescents with a wide range of estimated prevalence of 1-25%. Little is known about the role of the immune system in long COVID. However, one of the main hypotheses about the underlying mechanism in long COVID is that there is an immune and inflammatory dysregulation that persists after the acute infection. The objective of this study is to compare immune cells populations, and inflammatory biomarkers in paediatric populations with and without long COVID. Method(s): We analyzed 55 blood samples from the pediaCOVID cohort (Hospital Germans Trias i Pujol), which includes more than 130 children diagnosed with long COVID and 23 controls. We measured different immune cell populations using spectral cytometry with a panel of 37 cellular markers, and 42 inflammatory markers using Luminex or ELISA. EdgeR was used for statistical analysis of the spectral data;p-values of inflammatory markers were calculated using the likelihood ratio test and they were corrected for multiple comparisons. Result(s): The study cohort had a median age of 14.3 (IQR, 12.5-15.2) and 69.1% female. Patients had at least 3 symptoms associated with long COVID (median [IQR];10 [7-16]). The most common symptom was asthenia/fatigue (98.2%). Compared to the control cohort, children with long COVID had increased numbers of CD4+CD8+ T cells, IgA+CD21+CD27+ memory B cells, and IgA+CD21-CD27- memory B cells, while CD4+ TEMRA cells (CD45RA+, CCR7-), intermediate monocytes (CD14+, CD16+) and classical monocytes (CD14+, CD16-) were decreased (all p< 0.05;q=n.s.). None of the 42 inflammatory biomarkers showed significant differences between children with and without long COVID. Conclusion(s): The results of this study suggest that specific populations of peripheral blood immune cells might be involved in the mechanisms underlying prolonged COVID in children and adolescents. The increase in both IgA+CD21-CD27- and IgA+CD21+CD27+ memory B cells could be associated with the persistence of viral antigen in the gut and/or gut dysbiosis. Moreover, the decrease in CD4+ TEMRA cells could be related to autoantibodies against G-protein coupled receptors (GPCRs), since this cell population can express GPR56, and autoantibodies against GPCRs were previously reported to be elevated in adults with long COVID.

Association of gut microbial dysbiosis with disease severity, response to therapy and disease outcomes in Indian patients with COVID-19.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is associated with systemic hyper-inflammation. An adaptive interaction between gut microbiota and host immune systems is important for intestinal homeostasis and systemic immune regulation. The association of gut microbial composition and functions with COVID-19 disease severity is sparse, especially in India. We analysed faecal microbial diversity and abundances in a cohort of Indian COVID-19 patients to identify key signatures in the gut microbial ecology in patients with severe COVID-19 disease as well as in response to different therapies. The composition of the gut microbiome was characterized using 16Sr RNA gene sequences of genomic DNA extracted from faecal samples of 52 COVID-19 patients. Metabolic pathways across the groups were predicted using PICRUSt2. All statistical analyses were done using Vegan in the R environment. Plasma cytokine abundance at recruitment was measured in a multiplex assay. RESULTS: The gut microbiome composition of mild and severe patients was found to be significantly different. Immunomodulatory commensals, viz. Lachnospiraceae family members and Bifidobacteria producing butyrate and short-chain fatty acids (SCFAs), were under represented in patients with severe COVID-19, with an increased abundance of opportunistic pathogens like Eggerthella. The higher abundance of Lachnoclostridium in severe disease was reduced in response to convalescent plasma therapy. Specific microbial genera showed distinctive trends in enriched metabolic pathways, strong correlations with blood plasma cytokine levels, and associative link to disease outcomes. CONCLUSION: Our study indicates that, along with SARS-CoV-2, a dysbiotic gut microbial community may also play an important role in COVID-19 severity through modulation of host immune responses.

Microbiota shaping and bioburden monitoring of indoor antimicrobial surfaces

Indoor residents are constantly exposed to dynamic microbiota that have significant health effects. In addition to hand hygiene, cleaning, and disinfection, antimicrobial coatings (AMCs) can prevent the spread of infectious diseases in public areas. The sustainable use of antimicrobial-coated products requires an assessment of their pros and cons for human health and the environment. The toxicity and resistance risks of AMCs have been considered, but large-scale genetic studies on the microbial community compositions and resistomes of AMCs are scarce. The use of an AMC can reduce the total number of microbes on a surface but poses the risk of dysbiosis, microbial imbalance, such as the polarized growth of metallophilic, metal- and antimicrobial-resistant, and other survivor bacteria, and the overall reduction of microbial diversity. Loss of diversity may lead to the enrichment of harmful bacteria and an increased risk of communicable or immunological non-communicable inflammatory diseases (NCDs). In public buildings, such as kindergartens and nursing homes for the elderly, the use of AMCs is likely to increase due to epidemics and pandemics in recent years. Therefore, comprehensive metagenomic research is needed to monitor the effects of AMCs on indoor microbial community compositions and functions. Although the determination of good indoor microbiota and homeostasis is difficult, microbial communities that have health-protective or harmful effects can and should be identified using a metagenomic sequencing approach before the large-scale implementation of AMCs.

Advances in molecular diagnostic tests for community-acquired pneumonia

The use of a timely and appropriate antibiotic therapy, which requires early and accurate microorganisms' detection in pneumonia. Currently, the identification of microorganisms in pneumonia is limited by the low sensitivity and long response time of standard culture-based diagnostic tools. For this reason, treatment in pneumonia is empirical. An inadequate empirical treatment is related to poor outcomes in patients with pneumonia. The microbiological diagnosis is key to improve the outcomes in patient with pneumonia. Over the past years there was a significant advance in the molecular diagnosis of infectious diseases including pneumonia. Also the impact of the COVID-19 pandemic has impacted the development and application of these new molecular techniques. This review summarizes the advances in molecular diagnosis of community-acquired pneumonia.Copyright © 2022 EDIZIONI MINERVA MEDICA.

Polycystic Ovary Syndrome and COVID-19.

Polycystic ovary syndrome (PCOS) is generally characterized by hyperandrogenism, obesity, chronic low-grade inflammation, abnormalities in carbohydrate and lipid metabolism, vit. D deficiency and gut microbiota dysbiosis. Each of the aforementioned disturbances might be considered as a risk factor for increased SARS-CoV-2 susceptibility and more severe COVID-19 infection in women with PCOS. Hyperandrogenism is thought to play an essential role for determining the grade of susceptibility as well as the risk of severe COVID-19 infection in PCOS. It could be explained by the expression of a specific cellular co-receptor - transmembrane serine protease-2 (TMPRSS2), the process of androgen-dependent immune modulation and that of the stimulated renin-angiotensin system (RAS). Android obesity, commonly seen in PCOS, represents a condition of chronic low-grade inflammation that leads to the development of immune dysfunction and increased sensitivity to SARS-CoV-2 among the carriers of this syndrome. In addition, vit. D deficiency and gut dysbiosis have been described as other potential pathophysiological factors contributing to an increased risk for severe COVID-19 in women with PCOS.Copyright © 2022 Medical Information Center. All rights reserved.

The Role of Probiotics and Their Metabolites in the Treatment of Depression.

Depression is a common and complex mental and emotional disorder that causes disability, morbidity, and quite often mortality around the world. Depression is closely related to several physical and metabolic conditions causing metabolic depression. Studies have indicated that there is a relationship between the intestinal microbiota and the brain, known as the gut-brain axis. While this microbiota-gut-brain connection is disturbed, dysfunctions of the brain, immune system, endocrine system, and gastrointestinal tract occur. Numerous studies show that intestinal dysbiosis characterized by abnormal microbiota and dysfunction of the microbiota-gut-brain axis could be a direct cause of mental and emotional disorders. Traditional treatment of depression includes psychotherapy and pharmacotherapy, and it mainly targets the brain. However, restoration of the intestinal microbiota and functions of the gut-brain axis via using probiotics, their metabolites, prebiotics, and healthy diet may alleviate depressive symptoms. Administration of probiotics labeled as psychobiotics and their metabolites as metabiotics, especially as an adjuvant to antidepressants, improves mental disorders. It is a new approach to the prevention, management, and treatment of mental and emotional illnesses, particularly major depressive disorder and metabolic depression. For the effectiveness of antidepressant therapy, psychobiotics should be administered at a dose higher than 1 billion CFU/day for at least 8 weeks.

Probiotic therapy, African fermented foods and food-derived bioactive peptides in the management of SARS-CoV-2 cases and other viral infections.

The current paper focuses on the impact of probiotics, African fermented foods and bioactive peptides on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection severity and related viral infections. Using probiotics or bioactive peptides as therapeutic adjuncts appears superior to standard care alone. Probiotics play critical roles in innate and adaptive immune modulation by balancing the gut microbiota to combat viral infections, secondary bacterial infections and microbial dysbiosis. African fermented foods contain abundant potential probiotic microorganisms such as the lactic acid bacteria (LAB), Saccharomyces, and Bacillus. More so, fermented food-derived bioactive peptides play vital roles in preventing cardiovascular diseases, hypertension, lung injury, diabetes, and other COVID-19 comorbidities. Regularly incorporating potential probiotics and bioactive peptides into diets should enable a build-up of the benefits in the body system that may result in a better prognosis, especially in COVID-19 patients with underlying complexities. Despite the reported therapeutic potentials of probiotics and fermented foods, numerous setbacks exist regarding their application in disease management. These shortfalls underscore an evident need for more studies to evaluate the specific potentials of probiotics and traditional fermented foods in ameliorating SARS-CoV-2 and other viral infections.

Dysbiosis of oropharyngeal microbiome and antibiotic resistance in hospitalized COVID-19 patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is ongoing and multiple studies have elucidated its pathogenesis, however, the related- microbiome imbalance caused by SARS-CoV-2 is still not clear. In this study, we have comprehensively compared the microbiome composition and associated function alterations in the oropharyngeal swabs of healthy controls and coronavirus disease 2019 (COVID-19) patients with moderate or severe symptoms by metatranscriptomic sequencing. We did observe a reduced microbiome alpha-diversity but significant enrichment of opportunistic microorganisms in patients with COVID-19 compared with healthy controls, and the microbial homeostasis was rebuilt following the recovery of COVID-19 patients. Correspondingly, less functional genes in multiple biological processes and weakened metabolic pathways such as carbohydrate metabolism, energy metabolism were also observed in COVID-19 patients. We only found higher relative abundance of limited genera such as Lachnoanaerobaculum between severe patients and moderate patients while no worthy-noting microbiome diversity and function alteration were observed. Finally, we noticed that the co-occurrence of antibiotic resistance and virulence was closely related to the microbiome alteration caused by SRAS-CoV-2. Overall, our findings demonstrate that microbial dysbiosis may enhance the pathogenesis of SARS-CoV-2 and the antibiotics treatment should be critically considered.

Effects of Gut Microbiome Modulation on Reducing Adverse Health Outcomes among Elderly and Diabetes Patients during the COVID-19 Pandemic: A Randomised, Double-Blind, Placebo-Controlled Trial (IMPACT Study).

Gut microbiota is believed to be a major determinant of health outcomes. We hypothesised that a novel oral microbiome formula (SIM01) can reduce the risk of adverse health outcomes in at-risk subjects during the coronavirus disease 2019 (COVID-19) pandemic. In this single-centre, double-blind, randomised, placebo-controlled trial, we recruited subjects aged ≥65 years or with type two diabetes mellitus. Eligible subjects were randomised in a 1:1 ratio to receive three months of SIM01 or placebo (vitamin C) within one week of the first COVID-19 vaccine dose. Both the researchers and participants were blinded to the groups allocated. The rate of adverse health outcomes was significantly lower in the SIM01 group than the placebo at one month (6 [2.9%] vs. 25 [12.6], p < 0.001) and three months (0 vs. 5 [3.1%], p = 0.025). At three months, more subjects who received SIM01 than the placebo reported better sleep quality (53 [41.4%] vs. 22 [19.3%], p < 0.001), improved skin condition (18 [14.1%] vs. 8 [7.0%], p = 0.043), and better mood (27 [21.2%] vs. 13 [11.4%], p = 0.043). Subjects who received SIM01 showed a significant increase in beneficial Bifidobacteria and butyrate-producing bacteria in faecal samples and strengthened the microbial ecology network. SIM01 reduced adverse health outcomes and restored gut dysbiosis in elderly and diabetes patients during the COVID-19 pandemic.

Intestinal barrier dysfunction as a key driver of severe COVID-19.

The intestinal lumen harbors a diverse consortium of microorganisms that participate in reciprocal crosstalk with intestinal immune cells and with epithelial and endothelial cells, forming a multi-layered barrier that enables the efficient absorption of nutrients without an excessive influx of pathogens. Despite being a lung-centered disease, severe coronavirus disease 2019 (COVID-19) affects multiple systems, including the gastrointestinal tract and the pertinent gut barrier function. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can inflict either direct cytopathic injury to intestinal epithelial and endothelial cells or indirect immune-mediated damage. Alternatively, SARS-CoV-2 undermines the structural integrity of the barrier by modifying the expression of tight junction proteins. In addition, SARS-CoV-2 induces profound alterations to the intestinal microflora at phylogenetic and metabolomic levels (dysbiosis) that are accompanied by disruption of local immune responses. The ensuing dysregulation of the gut-lung axis impairs the ability of the respiratory immune system to elicit robust and timely responses to restrict viral infection. The intestinal vasculature is vulnerable to SARS-CoV-2-induced endothelial injury, which simultaneously triggers the activation of the innate immune and coagulation systems, a condition referred to as "immunothrombosis" that drives severe thrombotic complications. Finally, increased intestinal permeability allows an aberrant dissemination of bacteria, fungi, and endotoxin into the systemic circulation and contributes, to a certain degree, to the over-exuberant immune responses and hyper-inflammation that dictate the severe form of COVID-19. In this review, we aim to elucidate SARS-CoV-2-mediated effects on gut barrier homeostasis and their implications on the progression of the disease.