Microbiome & Chronic Diseases

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Disease ⇒ Covid-19 {40000510}

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- There is an unusual microbiomes in hospitalized COVID-19 patients.
- There is a strong connection between gut microbes and COVID-19 severity.
- In addition to the lungs and gut, the SARS-CoV-2 virus has been detected in the liver, kidney, heart, and brain.
- Intestinal bacteria appear to influence the production of this important mucus barrier, which could prevent viruses in the gut from reaching other parts of the body.
- Dysbiome can predispose to leaky gut and it is highly likely that viruses get access to organs other than the lungs and the gut through a leaky gut.
- SARS-CoV-2 altered the gut microbiome by the tenth day of infection; with some of the changes persisting after 26 days.
- There is a drop in bacterial species known to make short-chain fatty acids (SCFAs), which are important molecules that can regulate the immune system.
- SCFAs produced by gut microbes in mouse travel via the bloodstream to other areas of the body, including the lungs, and can protect the from respiratory viruses.
- Some bacteria manufacture a bacteriocin, that blocks the entry of viruses.
- Bacteroidetes trigger intestinal immune cells to release interferons. Interferons are key factors that ramp up the body’s response to viruses and help eliminate cells that are infected.

Shared Reference Notes

  • [1.1
    - Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution.
  • [1.2
    - A disrupted gut microbiome (gut dysbiosis) can lead to epithelium breakdown and inflammation, which have been shown to increase levels of angiotensin-converting enzyme 2 (ACE2), the target of SARS-CoV-2. - Increased gut permeability can lead to pro-inflammatory bacterial products to leak out and circulate systemically, triggering inflammatory cascades. - A specific gut microbiota composition may predispose healthy individuals to severe COVID-19 infections; increased levels of pro-inflammatory bacterial species correlated with elevated levels of pro-inflammatory cytokines and increased disease severity. - A disrupted gut microbiome may also contribute to increased pro-inflammatory cytokine production (“cytokine storm”), known to worsen severity of SARS-CoV-2 infection. - Proteomic and metabolomic profiling has shown progression to severe COVID-19 infection can be predicted both in infected patients and in healthy individuals. - Elderly and immunocompromised populations are known to have reduced microbiota diversity. Since many of these vulnerable patients have had worse clinical outcomes for COVID-19, this strengthens the possibility that the gut microbiome is affecting clinical progression. - Reduced gut microbiome diversity may therefore be useful as a predictive biomarker of COVID-19 severity. Mechanisms underpinning gastrointestinal symptoms are thought to involve ACE2 receptors, which are highly expressed on intestinal epithelial cells , in particular the brush border membrane of small intestinal enterocytes. - ACE2 gene expression has been shown to increase with age, potentially accounting for differential susceptibility to more severe disease.
  • [1.3
    - #Bacteroidetes trigger intestinal immune cells to release interferons. Interferons are key factors that ramp up the body’s response to viruses and help eliminate cells that are infected. - #Bacteroidetes have a specific molecule on their cell surface called a #Glycolipid that causes intestinal immune cells to release antiviral interferons.
  • - #Streptomycetes bacteria manufacture a bacteriocin, called duramycin, that blocks the entry of West Nile, dengue, and Ebola viruses into their host cells. Other bacteriocins halt the replication of herpes simplex viruses.
  • [1.4
    - The gut microbiota of moderate and severe Covid-19 patients has: a) lower Firmicutes/Bacteroidetes ratio, b) higher abundance of Proteobacteria; and c) lower abundance of beneficial #Butyrate-producing bacteria such as Roseburia and Lachnospira genera.
  • [1.5
    - Faecal microbiota transplant (FMT) restores a damaged gut microbiome and may impact on immune responses,3 including in the respiratory system (‘gut–lung axis’); such microbiome-immune signalling may result in lung-epithelial resistance to SARS-CoV-2 - Patient 1: an 80-year-old man with multiple comorbidities, including prior CDI, was admitted to hospital with pneumonia/sepsis. Following meropenem treatment, pneumonic features resolved, but CDI relapse occurred. Sequential vancomycin treatment and nasojejunal FMT were administered. On the day of FMT, he developed further fever and C-reactive protein (CRP) increased; repeat microbiology cultures were negative, but SARS-CoV-2 PCR was positive. He commenced on remdesivir and convalescent plasma (CP). Unexpectedly, 2 days after FMT, the fever never recurred and his CRP decreased, without further pneumonia exacerbation. - Patient 2: a 19-year-old man with ulcerative colitis on immunosuppression was admitted to hospital because of a relapse of CDI. Vancomycin therapy was administered, and symptomatic improvement occurred; colonoscopic FMT was administered to prevent further recurrence. Fifteen hours post-FMT, he developed fever up to 39°C, with CRP and interleukin-6 (IL-6) levels increased; SARS-CoV-2 PCR returned positive. Subsequently, other than two isolated episodes of fever, his temperature did not exceed 36.6°C, and CRP and IL-6 normalised.
  • [1.6
  • [1.7
  • [1.8
  • [1.9
  • [#Butyrate
  • [1.11] [#Lactobacillus rhamnosus] [#Probiotic (Bifidobacter and Lactobacilus)
    - #Probiotic > Covid-19 > The proportion who developed symptoms was 26.4% with LGG versus 42.9% with placebo, a significant difference.
  • [1.12
    - Patients with very low #Vitamin D levels (< 30 nmol/L) had the highest risks for SARS-CoV-2 infection and also for severe COVID-19 when infected
  • [1.13] [#Influenza A, #Pneumonia, #Tuberculosis
  • [1.14] [#Leptin
  • [1.15
    - Severe Covid > higher abundance of four microbial species (i.e., #Burkholderia contaminans, #Bacteroides nordii, #Bifidobacterium longum, and #Blautia sp. CAG 257), six microbial pathways (e.g., glycolysis and fermentation), and 10 virulence genes > further associated with host immune response. - The abundance of Bu. contaminans > associated with higher levels of inflammation biomarkers and lower levels of immune cells. - human-origin proteins identified from both blood and fecal samples suggested gut barrier dysfunction in COVID-19 patients. - The circulating levels of #Lipopolysaccharide-binding protein increased in patients with severe illness > associated with circulating inflammation biomarkers and immune cells. - proteins of disease-related bacteria (e.g., B. longum) were detectable in blood samples from patients.
  • [1.16
    - Calcitriol > increasing anti-inflammatory IL-10 production in B cells and reduces T cell activation by B cells and decreasing pro-inflammatory markers such as TNFα, IL-1β, IL-6, and cyclooxygenase-2 (COX-2) > anti-inflammatory effect. - #Vitamin D > induces the expression of antimicrobial peptides such as cathelicidin 1 and defensin β4 in lung epithelia. - The biologically active hydroxyderivatives of #Vitamin D > inhibit the action of the TMPRSS2 (the serine protease found on the host cell that primes the spike protein, which then binds to the angiotensin-converting enzyme 2 (ACE2) receptors).
  • [1.17
    - Bifidobacterium and Clostridium were depleted in those in the ICU. - The most severe COVID-19 patients had reduced Neisseria, Rothia, and Prevotella. - In contrast, Salmonella, Scardovia, Serratia, and Pseudomonadaceae were more abundant in the nasopharynx of ICU patients compared with those with mild or moderate symptoms, - Alloprevotella, Catonella, Lachnoanaerobaculum, Oribacterium, multiple Prevotella, Treponema, and Unclassified Erysipelotrichaceae operational taxonomic units (OTUs) to be more abundant and Unclassified Chloroplast to be less abundant in patients with severe compared with those with mild COVID-19
  • - #Corynebacterium accolens is a common nose inhabitant - #Corynebacterium accolens incidence was significantly decreased in the URT of patients with SARS-CoV-2 compared with uninfected controls. #Corynebacterium accolens can inhibit Streptococcus pneumoniae and Staphylococcus aureus growth, possibly through triolein hydrolysis, which releases #Oleic acid. - In addition to inhibiting bacterial pathogens, #Oleic acid is capable of inhibiting other enveloped viruses, such as herpes and influenza. - Oleoylethanolamide, an #Oleic acid derivative, may inhibit the release of proinflammatory cytokines induced by SARS-CoV-2, potetially reducing the risk of a patient developing a cytokine storm, which is associated with severe disease and high mortality.
  • [1.18] [#Glycans
  • [1.19
  • [1.21
    - SARS-CoV-2-infected participants with #Corynebacterium/#Dolosigranulum-dominant microbiome profiles were less likely to have respiratory symptoms than infected participants with other nasopharyngeal microbiome profiles
  • [1.22
    - Oral Bifidobacterium, Lactobacillus, and Solobacterium, all of which were depleted in patients with severe COVID-19. Nasopharyngeal Paracoccus was depleted while nasopharyngeal Proteus, Cupravidus, and Lactobacillus were increased in patients with severe COVID-19.
  • - the abundance of oral #Bifidobacterium was negatively associated with plasma concentrations of known COVID-19 biomarkers interleukin 17F (IL-17F) and monocyte chemoattractant protein-1 (MCP-1)
  • [1.23
    - Methylcobalamin has a significant affinity to bind to the active site of the nsp12 protein of SARS-CoV-2, Thus, #Vitamin B12 may inhibit the RNA‐dependent RNA polymerase activity of nsp12 responsible for the replication of the viral genome.
  • [1.24
    - The serum #Zonulin levels of COVID-19 patients with the mild clinical course were lower than the healthy control group. Moreover, serum #Zonulin levels were not correlated with ESR, CRP, and other inflammation markers
  • [1.25
    -anti-inflammatory bacteria, including #Bifidobacteria species and #Eubacterium rectale, with lower severity, and pro-inflammatory bacteria such as #Prevotella copri with higher severity.
  • [1.26
    - #Paraprevotella colonization inhibits lethal infection with murine hepatitis virus-2, a mouse coronavirus that is dependent on trypsin and trypsin-like proteases for entry into host cells
  • [1.27
    - Covid-19 > Mortality was associated with increased representation of #Proteobacteria in the fecal microbiota and decreased concentrations of fecal #Secondary bile acids and #Desaminotyrosine (DAT). - A microbiome metabolic profile (MMP) that accounts for fecal #Secondary bile acids and #Desaminotyrosine concentrations was independently associated with progression of respiratory failure leading to mechanical ventilation.
  • [1.28] [#Parkinson’s Disease] [#Alpha-synuclein
    - overexpression of α-synuclein in PD patients may limit SARS-CoV-2 neuroinvasion and degeneration of dopaminergic neurons; however, on the other hand, this virus can speed up the α-synuclein aggregation.

References Notes

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Common References