Researchers from Universidad de Concepción-Chile have found that probiotics such as Limosilactobacillus Fermentum (UCO-979C) and Lacticaseibacillus Rhamnosus (UCO-25A) can not only prevent COVID-19 severity but can also be protective versus SARS-CoV-2 infections.
The study findings were published in the peer reviewed journal: Biology.
https://www.mdpi.com/2079-7737/12/3/384#B21-biology-12-00384
Dysbiosis
Changes in the diversity of the native GI microbiome, or dysbiosis, has been noted in patients with acute COVID-19 infection.35 , 47 , 48 Oral cavity and fecal studies have found less butyric acid-producing bacteria and more lipopolysaccharide-producing bacteria in patients with COVID-19 infection.35 , 36
After acute COVID-19 infection, patients have been found to deplete commensal anti-inflammatory gut bacteria, such as Faecalibacterium prausnitzii, Eubacterium rectale, and bifidobacteria, which remained low in fecal microbiota samples collected up to 30 days after diagnosis suggesting a long-term role in causing dysbiosis.
This reduction in gut commensal bacteria correlated with increased concentration of inflammatory markers (inflammatory cytokines, C reactive protein [CRP], lactate dehydrogenase, aspartate aminotransferase [AST], and gamma-glutamyl transferase).37
This is also supported by another study in which fecal microbiota samples of COVID-19 patients were followed postdischarge at 2 weeks and at 6 months; at 6 months, patients with COVID-19 infection continued to have decreased microbiome diversity and higher levels of CRP, correlated with an increased proinflammatory state with dysbiosis.38
The pathophysiological mechanism by which SARS-CoV-2 initiates dysbiosis is largely unknown. It is postulated that downregulation of ACE2 disrupts gut immunity and promotes inflammation, increasing the propensity for invasion by opportunistic gut bacteria and downstream cytokine storms.49 , 50
It is evident that further robust studies are needed to establish the molecular mechanisms of long COVID syndrome.
Gastrointestinal and hepatobiliary manifestations of long COVID syndrome
Abdominal Pain, Nausea and Vomiting, Diarrhea, Constipation
GI sequelae of acute COVID-19 infection include symptoms of abdominal pain (pooled prevalence 2.7%), nausea and vomiting (pooled prevalence 4.6%–10.3%), and diarrhea (pooled prevalence 7.4%–13.2%).51, 52, 53 The respective pooled frequencies of abdominal pain, nausea and vomiting, and diarrhea occurring in long COVID syndrome are 7% (95%CI: 0.03–0.11), and 5% (95%CI: 0.03–0.10).54 In a case-control study of 46,857 outpatients diagnosed with COVID-19 matched 1:1 with patients without COVID-19, patients with COVID-19 infection were 1.3 times more likely to experience abdominal pain or nausea and vomiting at 31 to 60 days after initial outpatient encounter.55 Most initial abdominal pain, nausea, vomiting, and diarrhea symptoms resolve by 3 to 6 months, at rates of 90.5% and 89.4%, respectively.56 More limited data exist regarding constipation as a GI manifestation of long COVID syndrome. Constipation has been shown to be a long COVID GI manifestation after acute COVID-19 infection; in a study of 147 patients without preexisting GI manifestations 6.8% developed new onset of constipation at a median follow-up of 106 days (IQR 78–141).57
Dyspepsia, Postinfectious Irritable Bowel Syndrome
Long COVID disorders of the gut–brain axis or functional GI disorders (FGID), including irritable bowel syndrome (IBS) and dyspepsia, are now being acknowledged.58 The development of FGID after episodes of viral gastroenteritis has been previously supported.59 Longer lasting symptoms of FGID are shown to occur after episodes of GI inflammation and dysbiosis, both of which occur after COVID-19 infection.49 , 59 , 60
Furthermore, mood disturbances are strongly and bidirectionally linked to FGID such as IBS,61 , 62 and patients commonly meet diagnostic criteria for depression, anxiety, and posttraumatic stress disorder after COVID-19 infection.63 Limited studies have examined the frequency of postinfectious IBS or dyspepsia; a meta-analysis reported 17% (95% CI, 0.06–0.37) for postinfectious IBS and 20% (95% CI 0.06–0.50) for dyspepsia.54
Postinfectious IBS, postinfectious functional dyspepsia, or both, were found at rates of 5.3%, 2.1%, and 1.8%, respectively, at 6 months in a case-control study of 280 patients.64 It is hypothesized that more patients will subsequently develop long COVID FGIDs based on the characteristic biological nature of COVID-19 infection that causes intestinal inflammation and dysbiosis in conjunction with environmental and psychological stressors.65
reference link :https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9940919/
Taking into consideration the ineffectiveness of anti-COVID-19 drugs and differences in the doses as well as the effectiveness of the vaccines, resulting from the advent of new variants, new therapeutic alternatives have been sought.
One of these proposed therapeutic alternatives is the administration of probiotics [4]; even more specifically, immunobiotics. Immunobiotics are probiotic strains capable of beneficially regulating the mucosal immune system [5].
Considering the fact that the intestinal microbiota may beneficially modulate intestinal immunity, as well as pulmonary immunity by means of the intestine–lung axis [6], there emerges the possibility of taking advantage of the immunomodulating properties of immunobiotic bacteria.
Immunobiotic bacteria, when colonizing the gastrointestinal tract of an individual, could induce a beneficial effect on the immune system of a host at both the gastrointestinal and respiratory systems. This result is due to the fact that the local immunological regulation by the specific microbiota of the gut has a long-range immunological impact that reaches the lung [7]. T
herefore, probiotics may provide a wide scope of benefits to consumers, including the prevention and treatment of infections of the upper respiratory tract [8].
Discussion
After gathering the precedents and information on SARS-CoV-2-caused infection, as well as the research performed at our Laboratory of Bacterial Pathogenicity at the University of Concepcion on the immunomodulating L. fermentum UCO-979C and L. rhamnosus UCO-25A strains, we can say that both strains may have a potential use against SARS-CoV-2 infection.
This statement is based on the evaluation of the effects and symptomatology of SARS-CoV-2-caused infection and the probiotic as well as immunomodulating characteristics of both strains. The deregulation of several cytokines during the course of SARS-CoV-2 infection triggers a “cytokine storm”, causing a deregulation of different components of the immune system, generating lung hyperinflammation, which may lead to the death of a patient.
Immunomodulating probiotic strains could have an effect on this deregulation through the intestine–lung axis, regulating the different cytokines and other components of the immune system, as stated in Section 3.8., possibly leading to the mitigation of lung hyperinflammation.
Moreover, SARS-CoV-2 virus infection can also cause gastrointestinal symptoms in nearly 10% of infected patients. These cases suffer intestinal dysbiosis, which is accompanied by the deregulation of cytokines and other components of the immune system. Confronting the symptomatology of intestinal SARS-CoV-2 infection, immunoregulatory probiotic strains could drive dysbiosis to a condition of eubiosis, reducing the gastrointestinal symptoms and regulating the proinflammatory as well as anti-inflammatory factors of the gastrointestinal immune system, as indicated in Section 3.8.
The bioinformatics analysis of L. fermentum UCO-979C and L. rhamnosus UCO-25A strains has allowed us, firstly, to observe the potentiality of both strains to be used as a possible complementary treatment against COVID-19. In addition to the immunomodulating effects already analyzed in this review, secondary metabolites have become highly relevant in the search for possible treatments against COVID-19 [89].
In this context, a bioinformatics search for genes associated with the regulation of the immune response and the inflammatory response was carried out. Several genes related to the synthesis and metabolism of butyrate, one of the short-chain fatty acids that have demonstrated several benefits in terms of the regulation of inflammation and immunomodulation [100], were found in L. fermentum UCO-979C.
In addition, genes related to the synthesis of secondary bile acids, which participate in the regulation of the immune and inflammatory responses [124], were also found in L. fermentum UCO-979C. On the other hand, L. rhamnosus UCO-25A may have genes that participate in the synthesis of butyrate and genes related to the synthesis and transport of other types of short-chain fatty acids besides butyrate [127].
In the first approach, no genes related to the synthesis of secondary bile salts were observed in L. rhamnosus UCO-25A, but genes related to the transport of these metabolites were found. Thus, an effect of this probiotic by means of this pathway cannot be ruled out yet.
Finally, as previously mentioned, bacteriocins have shown a positive effect on the reduction in SARS-CoV-2 infection, as is the case of plantaricin [77].
The in silico analysis demonstrated the presence of genes related to bacteriocins in both strains. Lincocin M18, a stimulator of the cytokine’s response in the lungs [122], was detected in L. fermentum UCO-979C. This same type of analysis detected an unidentified type of bacteriocin in L. rhamnosus UCO-25A. Since previous studies of our laboratory have demonstrated the presence of a bacteriocin of the acidocin type in this strain, both results may be correlated.
This analysis provides a good approach to the metabolites of the L. fermentum UCO-979C and L. rhamnosus UCO-25A strains, which could have an effect on infection by SARS-CoV-2, allowing us to better focus future studies to develop an immunobiotic to be used as a complement to treat COVID-19.
