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1.
Food Funct ; 13(5): 2846-2856, 2022 Mar 07.
Article in English | MEDLINE | ID: covidwho-1700242

ABSTRACT

Obesity is a serious global health issue, and the societal interventions during the COVID-19 pandemic may have perturbed energy homeostasis, which affects the condition of obesity. Tea is a traditional beverage in Asia and has been shown to provide many beneficial health effects. Oolong tea is semifermented, with its chemical composition comprising features of green (unfermented) and black (fermented) tea. Although green tea has anti-obesity properties, studies on the anti-obesity ability of oolong tea are still scarce. In this study, we analyzed the chemical composition of oolong tea extract (OTE) and investigated the effects of OTE on high-fat diet-induced obese rats. OTE contained more (-)-epigallocatechin-3-gallate, (-)-epigallocatechin, and (-)-gallocatechin-3-gallate than theaflavins and theasinensins. Rats fed with a high-fat diet (HFD) and treated with 0.5% OTE exhibited significantly reduced body weight and visceral fat weight compared with the HFD-only group. OTE also decreased adipocyte size, lipogenesis-related protein sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN) protein expression and increased thermogenesis-related protein peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and uncoupling protein 1 (UCP1) protein expression in epididymal adipose tissue compared with the HFD group. Moreover, the OTE groups had a significantly higher abundance of Candidatus arthromitus and Hydrogenoanaerobacterium and a lower abundance of Ruminococcus1, Oscillibacter, and Odoribacter compared with the HFD group. All these results show that OTE can alleviate weight gain by regulating lipid metabolism and modulating the distribution of the gut microbiota to decrease lipid accumulation in adipose tissue.


Subject(s)
Anti-Obesity Agents/pharmacology , Plant Extracts/pharmacology , Tea , Adipose Tissue/metabolism , Animals , Anti-Obesity Agents/chemistry , Diet, High-Fat , Disease Models, Animal , Gastrointestinal Microbiome/drug effects , Lipid Metabolism/drug effects , Male , Plant Extracts/chemistry , Rats , Rats, Sprague-Dawley
3.
Front Immunol ; 12: 765528, 2021.
Article in English | MEDLINE | ID: covidwho-1555219

ABSTRACT

Influenza vaccination is an effective public health measure to reduce the risk of influenza illness, particularly when the vaccine is well matched to circulating strains. Notwithstanding, the efficacy of influenza vaccination varies greatly among vaccinees due to largely unknown immunological determinants, thereby dampening population-wide protection. Here, we report that dietary fibre may play a significant role in humoral vaccine responses. We found dietary fibre intake and the abundance of fibre-fermenting intestinal bacteria to be positively correlated with humoral influenza vaccine-specific immune responses in human vaccinees, albeit without reaching statistical significance. Importantly, this correlation was largely driven by first-time vaccinees; prior influenza vaccination negatively correlated with vaccine immunogenicity. In support of these observations, dietary fibre consumption significantly enhanced humoral influenza vaccine responses in mice, where the effect was mechanistically linked to short-chain fatty acids, the bacterial fermentation product of dietary fibre. Overall, these findings may bear significant importance for emerging infectious agents, such as COVID-19, and associated de novo vaccinations.


Subject(s)
Dietary Fiber/pharmacology , Immunity, Humoral/drug effects , Influenza Vaccines/immunology , Influenza, Human/immunology , Adolescent , Adult , Animals , Dietary Fiber/metabolism , Fatty Acids, Volatile/metabolism , Fatty Acids, Volatile/pharmacology , Female , Fermentation , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/immunology , Humans , Immunogenicity, Vaccine , Influenza, Human/microbiology , Influenza, Human/prevention & control , Male , Mice , Middle Aged , Orthomyxoviridae/immunology , Seasons , Vaccination , Young Adult
4.
Food Funct ; 12(22): 11241-11249, 2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1545659

ABSTRACT

The discovery of psychobiotics has improved the therapeutic choices available for clinical mental disorders and shows promise for regulating mental health in people by combining the properties of food and medicine. A Pediococcus acidilactici strain CCFM6432 was previously isolated and its mood-regulating effect was investigated in this study. Viable bacteria were given to chronically stressed mice for five weeks, and then the behavioral, neurobiological, and gut microbial changes were determined. CCFM6432 significantly reduced stress-induced anxiety-like behaviors, mitigated hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, and reversed the abnormal expression of hippocampal phosphorylated CREB and the c-Fos protein. In particular, CCFM6432 improved the gut microbial composition by inhibiting the over-proliferated pathogenic bacteria (e.g., Escherichia-shigella) and promoting beneficial bacteria growth (e.g., Bifidobacterium). Lactic acid, rather than bacteriocin, was further confirmed as the key compound that determined the antimicrobial activity of CCFM6432. Collectively, these results first proved the psychobiotic potential of the Pediococcus acidilactici strain. Ingestion of CCFM6432, or fermented food containing it, may facilitate mental health management in daily life, especially during the COVID-19 pandemic.


Subject(s)
Anxiety/microbiology , Gastrointestinal Microbiome/drug effects , Hypothalamo-Hypophyseal System/drug effects , Lactic Acid/pharmacology , Pediococcus acidilactici , Probiotics/pharmacology , Animals , CREB-Binding Protein/metabolism , Hippocampus/metabolism , Mice , Mice, Inbred C57BL , Proto-Oncogene Proteins c-fos/metabolism
5.
Food Funct ; 12(22): 11241-11249, 2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1493239

ABSTRACT

The discovery of psychobiotics has improved the therapeutic choices available for clinical mental disorders and shows promise for regulating mental health in people by combining the properties of food and medicine. A Pediococcus acidilactici strain CCFM6432 was previously isolated and its mood-regulating effect was investigated in this study. Viable bacteria were given to chronically stressed mice for five weeks, and then the behavioral, neurobiological, and gut microbial changes were determined. CCFM6432 significantly reduced stress-induced anxiety-like behaviors, mitigated hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, and reversed the abnormal expression of hippocampal phosphorylated CREB and the c-Fos protein. In particular, CCFM6432 improved the gut microbial composition by inhibiting the over-proliferated pathogenic bacteria (e.g., Escherichia-shigella) and promoting beneficial bacteria growth (e.g., Bifidobacterium). Lactic acid, rather than bacteriocin, was further confirmed as the key compound that determined the antimicrobial activity of CCFM6432. Collectively, these results first proved the psychobiotic potential of the Pediococcus acidilactici strain. Ingestion of CCFM6432, or fermented food containing it, may facilitate mental health management in daily life, especially during the COVID-19 pandemic.


Subject(s)
Anxiety/microbiology , Gastrointestinal Microbiome/drug effects , Hypothalamo-Hypophyseal System/drug effects , Lactic Acid/pharmacology , Pediococcus acidilactici , Probiotics/pharmacology , Animals , CREB-Binding Protein/metabolism , Hippocampus/metabolism , Mice , Mice, Inbred C57BL , Proto-Oncogene Proteins c-fos/metabolism
6.
Int J Mol Sci ; 22(18)2021 Sep 08.
Article in English | MEDLINE | ID: covidwho-1403613

ABSTRACT

The importance of a healthy microbiome cannot be overemphasized. Disturbances in its composition can lead to a variety of symptoms that can extend to other organs. Likewise, acute or chronic conditions in other organs can affect the composition and physiology of the gut microbiome. Here, we discuss interorgan communication along the gut-lung axis, as well as interactions between lung and coronary heart diseases and between cardiovascular disease and the gut microbiome. This triangle of organs, which also affects the clinical outcome of COVID-19 infections, is connected by means of numerous receptors and effectors, including immune cells and immune-modulating factors such as short chain fatty acids (SCFA) and trimethlamine-N-oxide (TMAO). The gut microbiome plays an important role in each of these, thus affecting the health of the lungs and the heart, and this interplay occurs in both directions. The gut microbiome can be influenced by the oral uptake of probiotics. With an improved understanding of the mechanisms responsible for interorgan communication, we can start to define what requirements an 'ideal' probiotic should have and its role in this triangle.


Subject(s)
COVID-19 , Coronary Disease , Gastrointestinal Microbiome/drug effects , Lung Diseases , Probiotics/administration & dosage , Animals , COVID-19/microbiology , COVID-19/pathology , Coronary Disease/microbiology , Coronary Disease/pathology , Humans , Lung Diseases/microbiology , Lung Diseases/pathology
7.
Int Immunol ; 33(12): 787-790, 2021 11 25.
Article in English | MEDLINE | ID: covidwho-1398105

ABSTRACT

Dysbiosis is alterations in the microbial composition compared with a healthy microbiota and often features a reduction in gut microbial diversity and a change in microbial taxa. Dysbiosis, especially in the gut, has also been proposed to play a crucial role in the pathogenesis of a wide variety of diseases, including inflammatory bowel disease, colorectal cancer, cardiovascular disease, obesity, diabetes and multiple sclerosis. A body of evidence has shown that intestinal polymeric immunoglobulin A (IgA) antibodies are important to regulate the gut microbiota as well as to exclude pathogenic bacteria or viral infection such as influenza and SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) at mucosal sites. Since the 1970s, trials for oral administration of therapeutic IgA or IgG have been performed mainly to treat infectious enteritis caused by pathogenic Escherichia coli or Clostridium difficile. However, few of them have been successfully developed for clinical application up to now. In addition to the protective function against intestinal pathogens, IgA is well known to modulate the gut commensal microbiota leading to symbiosis. Nevertheless, the development of therapeutic IgA drugs to treat dysbiosis is not progressing. In this review, the advantages of therapeutic IgA antibodies and the problems for their development will be discussed.


Subject(s)
Bacteria/drug effects , Gastrointestinal Microbiome/drug effects , Immunoglobulin A/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Intestines/drug effects , Animals , Bacteria/immunology , Dysbiosis , Host-Pathogen Interactions , Humans , Immunoglobulin A/adverse effects , Inflammatory Bowel Diseases/immunology , Inflammatory Bowel Diseases/microbiology , Intestines/immunology , Intestines/microbiology , Species Specificity
8.
Cells ; 10(6)2021 06 17.
Article in English | MEDLINE | ID: covidwho-1369745

ABSTRACT

Hypertension is associated with gut bacterial dysbiosis and gut pathology in animal models and people. Butyrate-producing gut bacteria are decreased in hypertension. RNA-seq analysis of gut colonic organoids prepared from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats was used to test the hypothesis that impaired interactions between the gut microbiome and gut epithelium are involved and that these would be remediated with butyrate supplementation. Gene expressions in immune responses including antigen presentation and antiviral pathways were decreased in the gut epithelium of the SHR in organoids and confirmed in vivo; these deficits were corrected by butyrate supplementation. Deficits in gene expression driving epithelial proliferation and differentiation were also observed in SHR. These findings highlight the importance of aligned interactions of the gut microbiome and gut immune responses to blood pressure homeostasis.


Subject(s)
Colon/microbiology , Dysbiosis , Gastrointestinal Microbiome/physiology , Hypertension/microbiology , Animals , Butyrates/pharmacology , Colon/drug effects , Gastrointestinal Microbiome/drug effects , Male , Organoids , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Transcriptome
9.
Biomed Pharmacother ; 141: 111896, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1300051

ABSTRACT

Influenza in humans is often accompanied by gastroenteritis-like symptoms. GeGen QinLian decoction (GQD), a Chinese herb formula, has been widely used to treat infectious diarrhea for centuries and has the effect of restoring intestinal flora. Studies have also reported that GQD were used to treat patients with influenza. However, whether regulating the intestinal flora is one of the ways GQD treats influenza has not been confirmed. In present research, we conducted a systemic pharmacological study, and the results showed that GQD may acts through multiple targets and pathways. In influenza-infected mice, GQD treatment reduced mortality and lung inflammation. Most importantly, the mortality and lung inflammation were also reduced in influenza-infected mice that have undergone fecal microbiota transplantation (FMT) from GQD (FMT-GQD) treated mice. GQD treatment or FMT-GQD treatment restores the intestinal flora, resulting in an increase in Akkermansia_muciniphila, Desulfovibrio_C21_c20 and Lactobacillus_salivarius, and a decrease in Escherichia_coli. FMT-GQD treatment inhibited the NOD/RIP2/NF-κB signaling pathway in the intestine and affected the expression of downstream related inflammatory cytokines in mesenteric lymph nodes (mLNs) and serum. In addition, FMT-GQD treatment showed systemic protection by restraining the inflammatory differentiation of CD4+ T cells. In conclusion, our study shows that GQD can affect systemic immunity, at least in part, through the intestinal flora, thereby protect the mice against influenza virus infectious pneumonia.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Gastrointestinal Microbiome/drug effects , Orthomyxoviridae , Pneumonia, Viral/drug therapy , Animals , CD4-Positive T-Lymphocytes/drug effects , Cytokines/metabolism , Female , Lymph Nodes/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Inbred NOD , NF-kappa B/drug effects , Pneumonia/etiology , Pneumonia/pathology , Pneumonia/prevention & control , Pneumonia, Viral/mortality , Receptor-Interacting Protein Serine-Threonine Kinase 2/drug effects , Signal Transduction/drug effects
10.
J Nutr Biochem ; 97: 108787, 2021 11.
Article in English | MEDLINE | ID: covidwho-1253236

ABSTRACT

The outbreak of mysterious pneumonia at the end of 2019 is associated with widespread research interest worldwide. The coronavirus disease-19 (COVID-19) targets multiple organs through inflammatory, immune, and redox mechanisms, and no effective drug for its prophylaxis or treatment has been identified until now. The use of dietary bioactive compounds, such as phenolic compounds (PC), has emerged as a putative nutritional or therapeutic adjunct approach for COVID-19. In the present study, scientific data on the mechanisms underlying the bioactivity of PC and their usefulness in COVID-19 mitigation are reviewed. In addition, antioxidant, antiviral, anti-inflammatory, and immunomodulatory effects of dietary PC are studied. Moreover, the implications of digestion on the putative benefits of dietary PC against COVID-19 are presented by addressing the bioavailability and biotransformation of PC by the gut microbiota. Lastly, safety issues and possible drug interactions of PC and their implications in COVID-19 therapeutics are discussed.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antioxidants/therapeutic use , COVID-19/therapy , Dietary Supplements , Gastrointestinal Microbiome , Phenols/therapeutic use , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antioxidants/pharmacokinetics , Antioxidants/pharmacology , Antiviral Agents/pharmacokinetics , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Biological Availability , Curcumin/pharmacokinetics , Curcumin/pharmacology , Curcumin/therapeutic use , Dietary Supplements/analysis , Gastrointestinal Microbiome/drug effects , Humans , Immunologic Factors/pharmacokinetics , Immunologic Factors/pharmacology , Immunologic Factors/therapeutic use , Phenols/pharmacokinetics , Phenols/pharmacology , Quercetin/pharmacokinetics , Quercetin/pharmacology , Quercetin/therapeutic use , Resveratrol/pharmacokinetics , Resveratrol/pharmacology , Resveratrol/therapeutic use , SARS-CoV-2/drug effects
11.
Int J Biol Macromol ; 183: 1753-1773, 2021 Jul 31.
Article in English | MEDLINE | ID: covidwho-1243010

ABSTRACT

The deficiency of chemical-synthesized antiviral drugs when applied in clinical therapy, such as drug resistance, and the lack of effective antiviral drugs to treat some newly emerging virus infections, such as COVID-19, promote the demand of novelty and safety anti-virus drug candidate from natural functional ingredient. Numerous studies have shown that some polysaccharides sourcing from edible and medicinal fungus (EMFs) exert direct or indirect anti-viral capacities. However, the internal connection of fungus type, polysaccharides structural characteristics, action mechanism was still unclear. Herein, our review focus on the two aspects, on the one hand, we discussed the type of anti-viral EMFs and the structural characteristics of polysaccharides to clarify the structure-activity relationship, on the other hand, the directly or indirectly antiviral mechanism of EMFs polysaccharides, including virus function suppression, immune-modulatory activity, anti-inflammatory activity, regulation of population balance of gut microbiota have been concluded to provide a comprehensive theory basis for better clinical utilization of EMFs polysaccharides as anti-viral agents.


Subject(s)
Agaricales/chemistry , Anti-Inflammatory Agents , Antiviral Agents , COVID-19/drug therapy , Fungal Polysaccharides , Immunologic Factors , SARS-CoV-2/immunology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/classification , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/chemistry , Antiviral Agents/classification , Antiviral Agents/therapeutic use , COVID-19/immunology , COVID-19/prevention & control , Fungal Polysaccharides/chemistry , Fungal Polysaccharides/classification , Fungal Polysaccharides/therapeutic use , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/immunology , Humans , Immunologic Factors/chemistry , Immunologic Factors/classification , Immunologic Factors/therapeutic use
12.
Rev Esp Quimioter ; 34(2): 81-92, 2021 Apr.
Article in Spanish | MEDLINE | ID: covidwho-1145772

ABSTRACT

From a microbiological point of view, both empirical and targeted antimicrobial treatment in respiratory infection is based on the sensitivity profile of isolated microorganisms and the possible resistance mechanisms that they may present. The latter may vary in different geographic areas according to prescription profiles and vaccination programs. Beta-lactam antibiotics, fluoroquinolones, and macrolides are the most commonly used antimicrobials during the exacerbations of chronic obstructive pulmonary disease and community-acquired pneumonia. In their prescription, different aspects such as intrinsic activity, bactericidal effect or their ability to prevent the development of resistance must be taken into account. The latter is related to the PK/PD parameters, the mutant prevention concentration and the so-called selection window. More recently, the potential ecological impact has grown in importance, not only on the intestinal microbiota, but also on the respiratory one. Maintaining the state of eubiosis requires the use of antimicrobials with a low profile of action on anaerobic bacteria. With their use, the resilience of the bacterial populations belonging to the microbiota, the state of resistance of colonization and the collateral damage related to the emergence of resistance to the antimicrobials in pathogens causing the infections and in the bacterial populations integrating the microbiota.


Subject(s)
Anti-Bacterial Agents/pharmacology , COVID-19/epidemiology , Drug Resistance, Bacterial , Pulmonary Disease, Chronic Obstructive/drug therapy , Respiratory Tract Infections/drug therapy , Administration, Oral , Anti-Bacterial Agents/administration & dosage , Chlamydophila pneumoniae/drug effects , Community-Acquired Infections/drug therapy , Community-Acquired Infections/microbiology , Disease Progression , Gastrointestinal Microbiome/drug effects , Haemophilus influenzae/drug effects , Humans , Microbial Sensitivity Tests , Moraxella catarrhalis/drug effects , Mycoplasma pneumoniae/drug effects , Pseudomonas aeruginosa/drug effects , Pulmonary Disease, Chronic Obstructive/microbiology , Respiratory Tract Infections/microbiology , Staphylococcus aureus/drug effects , Streptococcus pneumoniae/drug effects
13.
Pharmacol Res ; 167: 105548, 2021 05.
Article in English | MEDLINE | ID: covidwho-1135540

ABSTRACT

Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of agents, including Staphylococcal Enterotoxin B (SEB). Interestingly, a significant proportion of patients with COVID-19, also develop ARDS. In the absence of effective treatments, ARDS results in almost 40% mortality. Previous studies from our laboratory demonstrated that resveratrol (RES), a stilbenoid, with potent anti-inflammatory properties can attenuate SEB-induced ARDS. In the current study, we investigated the role of RES-induced alterations in the gut and lung microbiota in the regulation of ARDS. Our studies revealed that SEB administration induced inflammatory cytokines, ARDS, and 100% mortality in C3H/HeJ mice. Additionally, SEB caused a significant increase in pathogenic Proteobacteria phylum and Propionibacterium acnes species in the lungs. In contrast, RES treatment attenuated SEB-mediated ARDS and mortality in mice, and significantly increased probiotic Actinobacteria phylum, Tenericutes phylum, and Lactobacillus reuteri species in both the colon and lungs. Colonic Microbiota Transplantation (CMT) from SEB-injected mice that were treated with RES as well as the transfer of L. reuteri into recipient mice inhibited the production of SEB-mediated induction of pro-inflammatory cytokines such as IFN-γ and IL-17 but increased that of anti-inflammatory IL-10. Additionally, such CMT and L. reuteri recipient mice exposed to SEB, showed a decrease in lung-infiltrating mononuclear cells, cytotoxic CD8+ T cells, NKT cells, Th1 cells, and Th17 cells, but an increase in the population of regulatory T cells (Tregs) and Th3 cells, and increase in the survival of mice from SEB-mediated ARDS. Together, the current study demonstrates that ARDS induced by SEB triggers dysbiosis in the lungs and gut and that attenuation of ARDS by RES may be mediated, at least in part, by alterations in microbiota in the lungs and the gut, especially through the induction of beneficial bacteria such as L. reuteri.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Colon/drug effects , Enterotoxins , Fecal Microbiota Transplantation , Gastrointestinal Microbiome/drug effects , Lung/drug effects , Respiratory Distress Syndrome/prevention & control , Resveratrol/pharmacology , Superantigens , Animals , Cell Line , Colon/immunology , Colon/metabolism , Colon/microbiology , Cytokines/metabolism , Disease Models, Animal , Dysbiosis , Female , Inflammation Mediators/metabolism , Lactobacillus reuteri/drug effects , Lactobacillus reuteri/growth & development , Lung/immunology , Lung/metabolism , Lung/microbiology , Mice, Inbred C3H , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/microbiology
14.
Int J Mol Sci ; 22(5)2021 Mar 05.
Article in English | MEDLINE | ID: covidwho-1129733

ABSTRACT

While there are various kinds of drugs for type 2 diabetes mellitus at present, in this review article, we focus on metformin which is an insulin sensitizer and is often used as a first-choice drug worldwide. Metformin mainly activates adenosine monophosphate-activated protein kinase (AMPK) in the liver which leads to suppression of fatty acid synthesis and gluconeogenesis. Metformin activates AMPK in skeletal muscle as well, which increases translocation of glucose transporter 4 to the cell membrane and thereby increases glucose uptake. Further, metformin suppresses glucagon signaling in the liver by suppressing adenylate cyclase which leads to suppression of gluconeogenesis. In addition, metformin reduces autophagy failure observed in pancreatic ß-cells under diabetic conditions. Furthermore, it is known that metformin alters the gut microbiome and facilitates the transport of glucose from the circulation into excrement. It is also known that metformin reduces food intake and lowers body weight by increasing circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15). Furthermore, much attention has been drawn to the fact that the frequency of various cancers is lower in subjects taking metformin. Metformin suppresses the mechanistic target of rapamycin (mTOR) by activating AMPK in pre-neoplastic cells, which leads to suppression of cell growth and an increase in apoptosis in pre-neoplastic cells. It has been shown recently that metformin consumption potentially influences the mortality in patients with type 2 diabetes mellitus and coronavirus infectious disease (COVID-19). Taken together, metformin is an old drug, but multifaceted mechanisms of action of metformin have been unraveled one after another in its long history.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Metformin/pharmacology , Autophagy/drug effects , COVID-19/complications , COVID-19/mortality , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/etiology , Diabetes Mellitus, Type 2/mortality , Gastrointestinal Microbiome/drug effects , Humans , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Intracellular Signaling Peptides and Proteins/drug effects , Intracellular Signaling Peptides and Proteins/metabolism
15.
Nutrition ; 85: 111115, 2021 05.
Article in English | MEDLINE | ID: covidwho-1065510

ABSTRACT

Clinical manifestations of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can include gastrointestinal signals and symptoms. Individuals with previous clinical conditions that usually enroll gut dysbiosis have been identified as being at high risk to develop more severe infectious phenotypes. Actually, intestinal dysbiosis has been observed in infected patients and potentially linked to systemic hyperinflammation. These observations suggest that a previous gut dysbiosis may be aggravated by SARS-CoV-2 infection and related to progression of the coronavirus disease 2019 (COVID-19) into more severe stages. While COVID-19's pathophysiology is not fully understood, it seems relevant to consider the interactions of candidate therapeutic drugs with the host, gut microbiota, and SARS-CoV-2. Here we summarize scientific evidence supporting the potential relevance of these interactions and suggest that unfavorable clinical data on hydroxychloroquine administration in COVID-19 may have been influenced by the dose provided and its impact on gut dysbiosis. The proposition is based on preliminary data on gut microbiota composition from individuals with inactive systemic lupus erythematosus under exclusive continuous hydroxychloroquine treatment, displaying a direct correlation between drug doses and markers typically associated with gut dysbiosis.


Subject(s)
COVID-19/drug therapy , Dysbiosis/chemically induced , Gastrointestinal Microbiome/drug effects , Hydroxychloroquine/adverse effects , COVID-19/microbiology , Humans , Hydroxychloroquine/therapeutic use
16.
Diabetes Metab Syndr ; 15(1): 295-301, 2021.
Article in English | MEDLINE | ID: covidwho-1025696

ABSTRACT

BACKGROUND AND AIMS: Probiotics can support the body's systems in fighting viral infections. This review is aimed to focus current knowledge about the use of probiotics as adjuvant therapy for COVID-19 patients. METHODS: We performed an extensive research using the PubMed-LitCovid, Cochrane Library, Embase databases, and conducting manual searches on Google Scholar, Elsevier Connect, Web of Science about this issue. RESULTS: We have found several papers reporting data about the potential role of probiotics as well as contrasting experimental data about it. CONCLUSIONS: Most data show good results demonstrating that probiotics can play a significant role in fighting SARS-CoV-2 infection, also compared with their use in the past for various diseases. They seem effective in lowering inflammatory status, moreover in patients with chronic comorbidities such as cancer and diabetes, improving clinical outcomes.


Subject(s)
COVID-19/diet therapy , COVID-19/epidemiology , Gastrointestinal Microbiome/physiology , Probiotics/administration & dosage , Gastrointestinal Microbiome/drug effects , Humans , Treatment Outcome
17.
Front Cell Infect Microbiol ; 10: 576551, 2020.
Article in English | MEDLINE | ID: covidwho-979016

ABSTRACT

Infection with the SARS-CoV-2 virus causes cardiopulmonary and vascular complications, ranging in severity. Understanding the pathogenic mechanisms of the novel SARS-CoV2 infection and progression can provide potential novel targets for its prevention and/or treatment. Virus microbiota reciprocal interactions have been studied in a variety of viral infections. For example, the integrity of Coronavirus particles can be disrupted by surfactin, a bacterial surface molecule that targets other viruses, including that of influenza A. In this light, intestinal microbiota likely influences COVID-19 virulence, while from its side SARS-CoV-2 may affect the intestinal microbiome promoting dysbiosis and other deleterious consequences. Hence, the microbiota pre-existing health status and its alterations in the course of SARS-CoV-2 infection, are likely to play an important, still underscored role in determining individual susceptibility and resilience to COVID-19. Indeed, the vast majority of COVID-19 worst clinical conditions and fatalities develop in subjects with specific risk factors such as aging and the presence of one or more comorbidities, which are intriguingly characterized also by unhealthy microbiome status. Moreover, these comorbidities require complex pharmacological regimens known as "polypharmacy" that may further affect microbiota integrity and worsen the resilience to viral infections. This complex situation may represent a further and underestimated risk with regard to COVID-19 clinical burden for the elderly and comorbid people. Here, we discuss the possible biological, physiopathological, and clinical implications of gut microbiota in COVID-19 and the strategies to improve/maintain its healthy status as a simple and adjunctive strategy to reduce COVID-19 virulence and socio-sanitary burden.


Subject(s)
COVID-19/microbiology , Gastrointestinal Microbiome/physiology , Gastrointestinal Tract/microbiology , SARS-CoV-2/physiology , Age Factors , COVID-19/drug therapy , COVID-19/physiopathology , COVID-19/virology , Dysbiosis/microbiology , Dysbiosis/virology , Gastrointestinal Microbiome/drug effects , Gastrointestinal Tract/virology , Humans , Microbial Interactions , Risk Factors , Virulence
18.
Biochim Biophys Acta Mol Basis Dis ; 1867(3): 166037, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-966695

ABSTRACT

Hypertension is one of the most prevalent cardiovascular diseases worldwide. However, in the population of resistant hypertension, blood pressure is difficult to control effectively. Moreover, antihypertensive drugs may have adverse effect currently. Hence, new therapeutic targets and treatments are needed to uncovered and exploited to control hypertension and its comorbidities. In the past, classical drug targets, such as the aldosterone receptor, aldosterone synthase, and ACE2/angiotensin 1-7/Mas receptor axis, have been investigated. Recently, vaccines and drugs targeting the gastrointestinal microbiome, which represent drug classes, have also been investigated for the management of blood pressure. In this review, we summarized current knowledge on classical and new drug targets and discussed the potential utility of new drugs in the treatment of hypertension.


Subject(s)
Antihypertensive Agents/pharmacology , Drug Discovery , Hypertension/drug therapy , Molecular Targeted Therapy , Animals , Antihypertensive Agents/therapeutic use , Drug Development , Gastrointestinal Microbiome/drug effects , Humans , Hypertension/metabolism , Hypertension/microbiology , Hypertension/physiopathology , Renin-Angiotensin System/drug effects , Signal Transduction/drug effects
19.
Gastroenterology ; 160(1): 39-46, 2021 01.
Article in English | MEDLINE | ID: covidwho-936157

ABSTRACT

The role of angiotensin converting enzyme 2 has expanded from regulating the renin angiotensin system to regulating intestinal amino acid homeostasis and the gut microbiome. Recently, angiotensin converting enzyme 2 was identified as a primary receptor for severe acute respiratory syndrome coronaviruses 1 and 2 being expressed in multiple tissues including the luminal surface of the gut. In this brief perspective, we examine the role of angiotensin converting enzyme 2 as the receptor for severe acute respiratory syndrome coronavirus 2 and the impact of coronavirus disease 19 infection on the gut microbiome and on the gut epithelium.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/enzymology , Gastroenteritis/enzymology , Gastrointestinal Microbiome , Intestinal Mucosa/enzymology , Receptors, Virus/metabolism , SARS-CoV-2/pathogenicity , Angiotensin-Converting Enzyme 2/therapeutic use , Animals , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/microbiology , COVID-19/virology , Feces/microbiology , Feces/virology , Gastroenteritis/drug therapy , Gastroenteritis/microbiology , Gastroenteritis/virology , Gastrointestinal Microbiome/drug effects , Host-Pathogen Interactions , Humans , Intestinal Mucosa/drug effects , Intestinal Mucosa/microbiology , Intestinal Mucosa/virology , Renin-Angiotensin System , SARS-CoV-2/drug effects , Virus Internalization
20.
Life Sci ; 264: 118450, 2021 Jan 01.
Article in English | MEDLINE | ID: covidwho-885374

ABSTRACT

AIMS: Hydroxychloroquine (HCQ), a widely used antimalarial drug, is proposed to treat coronavirus disease 2019 (COVID-19). However, no report is currently available regarding the direct effects of HCQ on gut microbiota, which is associated with the outcomes of elderly patients with COVID-19. Here, we first investigated the effects of HCQ on intestinal microecology in mice. MAIN METHODS: Fifteen female C57BL/6J mice were randomly divided into two groups: HCQ group (n = 10) and control group (n = 5). Mice in the HCQ group were administered with HCQ at dose of 100 mg/kg by gavage daily for 14 days. The feces of mice were collected before and on the 7th and 14th days after HCQ challenge, and then analyzed by 16S rRNA amplicon sequencing. At the end of the experiment, the hematology, serum biochemistry and cytokines were determined, respectively. The mRNA expression of tight junction proteins in colonic tissues were also studied by RT-PCR. KEY FINDINGS: HCQ challenge had no effects on the counts of white blood cells, the levels of serum cytokines, and the gene expression of tight junction proteins in colon. HCQ also did not increase the content of serum d-lactate in mice. Notably, HCQ significantly decreased the diversity of gut microbiota, increased the relative abundance of phylum Bacteroidetes whereas decreased that of Firmicutes. SIGNIFICANCE: Short-term high dose HCQ challenge changes gut microbiota but not the intestinal integrity and immunological responses in mice. Special attention should be paid to the effects of HCQ on intestinal microecology in future clinical use.


Subject(s)
Colon/drug effects , Colon/immunology , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/immunology , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Administration, Oral , Animals , Colon/metabolism , Cytokines/blood , Cytokines/immunology , Feces/microbiology , Female , Lactic Acid/blood , Mice , RNA, Ribosomal, 16S/genetics , Tight Junction Proteins/biosynthesis
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