: A new meta study by researchers from University of Bari "Aldo Moro", Policlinico University Hospital of Bari-Italy, A. Xhuvani University of Elbasan-Albania and Riuniti University Hospital of Foggia-Italy have shown that probiotics play a vital role in the immune system and helps COVID-19 patients to recover faster leading to its possible role as adjuvants in COVID-19 treatment protocols.
The study findings were published in the peer reviewed Journal of Diabetes & Metabolic Syndrome: Clinical Research & Reviews
The meta study showed 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 and in patients with chronic comorbidities such as cancer and diabetes, the usage of probiotics improved clinical outcomes.
The term "microbiota" refers to the specific and unique composition (genera/species) of the microbial population and it differs from one person to another, and influences human health.
Importantly these microbes and the human body are inter-dependently associated. The crosstalk between the host and all the microbiota sites define several axes, such as the gut/lung or gut/brain or gut/skin. Changes in this microbiota are related to various infections and health issues.
Human microbiome must be considered as a “metabolic system” that interacts with the host and performs many necessary functions for human health. Continuous and reciprocal relationships (crosstalk) between the host and all the microbiota sites define several axes, such as the gut/lung or gut/brain or gut/skin. For instance, through the mesenteric lymphatic system, intact bacteria and their metabolites enter the systemic circulation and influence the pulmonary immune response (gut/lung axis). Through this way intestinal metabolites, mainly produced by bacterial fermentation of dietary fiber, such as short-chain fatty acids (SCFAs), significantly influence local gut immunity but also distant organs.
Importantly SCFAs derived from the gut are able to suppress lung inflammation.
The dendritic cells (DCs), the antigen-presenting cells of the mammalian immune system, stimulate T-cells subpopulations in mesenteric lymph nodes and gut lymphatic tissue to produce regulatory cytokines. After airways immune-stimulation, these T-cells move from the gut to the respiratory system, providing protection and stimulating an anti-inflammatory response In fact, gut microbiota rebalancing has been shown to reduce ventilator-associated enteritis and pneumonia.
The direct opposite to the healthy condition of eubiosis is the so called dysbiosis. The altered bacterial balance causes the translocation of cytokines, endotoxins and microbial metabolites in the general circulation to other organs, such as the lung. Conversely, respiratory inflammation (due to many causes, e.g., respiratory viral infections due to SARS-CoV-2), causes local dysbiosis and, in turn, the translocation of microbial metabolites and toxins to other organs, such as the gut. Physiological changes in the human microbiota with age leads to a “physiological dysbiosis”, with less diversification in microbial composition, aggravated in case of comorbidity (hypertension, diabetes, chronic inflammatory bowel diseases, etc.) https://www.frontiersin.org/articles/10.3389/fmicb.2015.01085/full
Therefore, to establish the condition of eubiosis, “good” bacteria are required.
From what is known, it appears that different factors (age, comorbidities, therapeutics, etc.) dysregulate the four communication axes of the gut/lung, gut/brain, and gut/skin and skin/brain microbiota, leading to a microbial imbalance in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients.
In this study led by Dr Luigi Santacroce and Dr Francesco Inchingolo, the study team attempts to address the many factors such as dysbiosis (imbalance in the microbiota) that could influence the SARS-CoV-2 infection course.
In order to investigate any alternative/ supporting therapeutic remedies in the fight against this virus, they analyze the available data on the association between SARS-CoV-2 and human microbiota in this review.
The study team performed extensive research using the PubMed-LitCovid, Cochrane Library, Embase databases and conducted manual searches on Google Scholar, Elsevier Connect, Web of Science about this issue.
Interestingly most of the data showed promising results demonstrating the benefits of probiotics in fighting the SARS-CoV-2 infection, as evident in the case of other diseases.
Dr Santacroce told Thailand Medical News, "In COVID-19 patients, probiotics could help to restore the altered gut microbiota, contributing to a healthy gut-lung axis."
It has been found that the most frequent symptoms of SARS-CoV-2 infection are fever, body aches, nasal congestion, dry cough, and sore throat. However, about 5-10% of patients suffer from gastrointestinal symptoms, such as nausea, vomiting, diarrhea, and abdominal pain.
Also other less frequent symptoms are total or partial loss of the sense of smell/taste, neurological symptoms, cerebrovascular events, neuropsychiatric symptoms and skin manifestations.
From the observed symptoms, one can hypothesize that SARS-CoV-2 interacts with the gut microbiota via the gut/lung axis.
The study team believes it could also be responsible for neuropsychiatric and cutaneous manifestations through the gut/brain and gut/ skin, and skin/brain axes.
As observed with the viral entry into the host cell, leading to lung damage and the subsequent series of reactions that end in an altered expression of antimicrobial peptides on Paneth's intestinal cells ie an alteration that modifies the composition of the intestinal microbiota, it is evident that the virus is influencing the gut/lung crosstalk.
It is also important to consider that antibiotics and antivirals are often given to patients with SARS-Cov-2 infection, which could result in further gut microbiota dysbiosis.
Therefore, dysregulated inflammation and intestinal dysbiosis is caused not only by the infection itself. Indeed, comorbidities or the patient’s age may be the causes that lead to a greater severity of the disease and poor results in therapy.
This may be one of the reasons for the increased severity of COVID-19 due to the direct regulation of crosstalk between the intestine, lung, brain, and skin, which increases immune dysregulation.
Hence all this leads to the translocation of pathogenic organisms through the intestinal mucosa and secondary bacterial infections. Consequently, the increased inflammatory response leads to multi-organ dysfunction with poor clinical outcome.
Indeed, in the SARS-Cov-2 was observed, in several studies, that the intestinal microbiome presented bacterial diversity. It is reported that there is a higher number of opportunistic pathogenic population, such as Actinomyces, Streptococcus, Rothia, Veillonella, Clostridium hathewayi, Actinomyces viscosus, Bacteroides nordii
and reduced Eubacterium ventriosum, Faecalibacterium
. It is also noted that the excessive presence of Coprobacillus
, Clostridium ramosum
and Clostridium hathewayi
related to the severity of the prognosis. Instead, there is an inverse relationship between the excessive presence of Faecalibacterium prausnitzii,
acting as inflammatory activator, and the severity of the infection. https://www.sciencedirect.com/science/article/pii/S0016508520347016
Also in other studies, in the fecal microbiome was found that Lactobacillus, Bifidobacterium
, Streptococcus, Clostridium, Firmicutes, Corynebacterium, Ruthenibacterium
were over represented, and the Lactobacillus, Bifidobacterium, Coprococcus, Parabacteroides, Roseburia, Faecalibacterium
has a potential influence on the intestinal ACE2 expression, and Bacteroides dorei, Bacteroides thetaiotaomicron, Bacteroides massiliensis
and Bacteroides ovatus
, have shown an inverse correlation with the fecal load of SARS-Cov-2 and a protective effect against inflammation. https://europepmc.org/article/pmc/pmc7542326
The study team in this context, report several studies where the intestinal microbiome presented bacterial diversity in SARS-CoV-2 cases, correlating directly or inversely.
This kind of bidirectional link is also observed between the intestinal microbiota and the skin. A SARS-Cov-2 patient manifesting skin symptoms may have alterations of the gut microbiota, that partly justify their presence to the immune process of gut/skin crosstalk.
For while now, it is well established that probiotics strengthen and modulate the immune system, contribute to repopulating the gut with "good" bacteria, hinder pathogen proliferation, and help to establish a condition of eubiosis (microbial balance in the body).
Typically the term probiotics include many species, such as Lactobacillus spp., Bifidobacterium spp, Enterococcus spp, and Saccharomyces spp, Leuconostoc, Pediococcus. The Lactobacillus spp. (L. rhamnosus) and Bifidobacterium spp. (B. lactis HN019) are commonly found in fermented products, such as yogurts and cheeses.
The study team advocates based on this study the usage of probiotics, and their metabolites SCFAs (short-chain fatty acids), to reinforce innate and adaptive immunity in SARS-CoV-2 patients. It can be an adjuvant strategy against complications.
Also the administration of probiotics is observed to increase anti-inflammatory cytokines, decrease pro-inflammatory cytokines, improve antiviral antibody production, and reduce the viral load. Taking probiotics has immensely improved the condition of the clinical patient, too, in many cases. These observations indicate that the probiotics would be useful in reducing SARS-CoV-2 dissemination in the respiratory tract and gut, reinforcing both anti-inflammatory responses and immune defenses.
In summary, this review aims to focus on current knowledge about the use of probiotics as adjuvant therapy for COVID-19 patients. The probiotics seem effective in lowering inflammatory status, moreover in patients with chronic comorbidities such as cancer and diabetes, improving clinical outcomes, the team concludes.
The proven efficacy of probiotics was already demonstrated in the past in various diseases, including the viral ones, specially their anti-inflammatory and immune-stimulatory effects. Immunomodulatory benefits are particularly relevant for people at risk of developing SARS-CoV-2 severe disease. In this case, they exhibit excessive inflammatory responses and complications, especially in case of comorbidities. Moreover, probiotics are available and not expensive, easy to administer orally, without side effects or therapeutic interferences. Hence, they are a potential therapeutic strategy that must considered in supporting moderate and severe cases of SARS-CoV-2. Some authors also recommend their administration in mechanically ventilated patients and in advance for a better prognosis and outcome.
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