Fusobacterium nucleatum Pyogenic Liver Abscess and the Role of Bacterial Virulence and Gut Microbiota Dysbiosis.

In the United States, pyogenic liver abscesses are often due to monomicrobial infection and are rarely documented to be a consequence of Fusobacterium infection, a common cause of Lemierre's syndrome. Recent advances in gut microbial studies have identified Fusobacterium as a commensal gut flora that becomes pathogenic in the setting of dysbiosis resulting from colorectal diseases, such as diverticulitis. While the bacteria's tropism for the liver remains to be elucidated, the virulence pattern of Fusobacterium and the portal venous drainage system have allowed us to understand the bacterium's propensity for causing right hepatic abscesses. In this case report, we detail an immunocompetent man with a history of sigmoid diverticulitis who developed a right hepatic abscess due to Fusobacterium nucleatum, while delineating a review of the literature on the virulent properties of the bacterium and the impact of gut microbiota dysbiosis in its pathogenicity. A descriptive analysis was also performed to identify the characteristics of patients who are at risk in hopes of further improving the clinical diagnostic schema for this condition.

Neuropathy in COVID-19 associated with dysbiosis-related inflammation.

Although COVID-19 affects mainly lungs with a hyperactive and imbalanced immune response, gastrointestinal and neurological symptoms such as diarrhea and neuropathic pains have been described as well in patients with COVID-19. Studies indicate that gut-lung axis maintains host homeostasis and disease development with the association of immune system, and gut microbiota is involved in the COVID-19 severity in patients with extrapulmonary conditions. Gut microbiota dysbiosis impairs the gut permeability resulting in translocation of gut microbes and their metabolites into the circulatory system and induce systemic inflammation which, in turn, can affect distal organs such as the brain. Moreover, gut microbiota maintains the availability of tryptophan for kynurenine pathway, which is important for both central nervous and gastrointestinal system in regulating inflammation. SARS-CoV-2 infection disturbs the gut microbiota and leads to immune dysfunction with generalized inflammation. It has been known that cytokines and microbial products crossing the blood-brain barrier induce the neuroinflammation, which contributes to the pathophysiology of neurodegenerative diseases including neuropathies. Therefore, we believe that both gut-lung and gut-brain axes are involved in COVID-19 severity and extrapulmonary complications. Furthermore, gut microbial dysbiosis could be the reason of the neurologic complications seen in severe COVID-19 patients with the association of dysbiosis-related neuroinflammation. This review will provide valuable insights into the role of gut microbiota dysbiosis and dysbiosis-related inflammation on the neuropathy in COVID-19 patients and the disease severity.

Pathophysiological mechanisms underlying gastrointestinal symptoms in patients with COVID-19.

Gastrointestinal (GI) symptoms, such as diarrhea, abdominal pain, vomiting, and anorexia, are frequently observed in patients with coronavirus disease 2019 (COVID-19). However, the pathophysiological mechanisms connecting these GI symptoms to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections remain elusive. Previous studies indicate that the entry of SARS-CoV-2 into intestinal cells leads to downregulation of angiotensin converting enzyme 2 (ACE2) receptors resulting in impaired barrier function. While intestinal ACE2 functions as a chaperone for the amino acid transporter B0AT1, the B0AT1/ACE2 complex within the intestinal epithelium acts as a regulator of gut microbiota composition and function. Alternations to the B0AT1/ACE2 complex lead to microbial dysbiosis through increased local and systemic immune responses. Previous studies have also suggested that altered serotonin metabolism may be the underlying cause of GI disorders involving diarrhea. The findings of elevated plasma serotonin levels and high fecal calprotectin in COVID-19 patients with diarrhea indicate that the viral infection evokes a systemic inflammatory response that specifically involves the GI. Interestingly, the elevated proinflammatory cytokines correlate with elevated serotonin and fecal calprotectin levels further supporting the evidence of GI inflammation, a hallmark of functional GI disorders. Moreover, the finding that rectal swabs of COVID-19 patients remain positive for SARS-CoV-2 even after the nasopharynx clears the virus, suggests that viral replication and shedding from the GI tract may be more robust than that of the respiratory tract, further indicating fecal-oral transmission as another important route of viral spread. This review summarized the evidence for pathophysiological mechanisms (impaired barrier function, gut inflammation, altered serotonin metabolism and gut microbiota dysbiosis) underlying the GI symptoms in patients with COVID-19.

Is Gut Microbiota Dysbiosis a Predictor of Increased Susceptibility to Poor Outcome of COVID-19 Patients? An Update.

The scientific knowledge already attained regarding the way severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human cells and the clinical manifestations and consequences for Coronavirus Disease 2019 (COVID-19) patients, especially the most severe cases, brought gut microbiota into the discussion. It has been suggested that intestinal microflora composition plays a role in this disease because of the following: (i) its relevance to an efficient immune system response; (ii) the fact that 5-10% of the patients present gastrointestinal symptoms; and (iii) because it is modulated by intestinal angiotensin-converting enzyme 2 (ACE2) (which is the virus receptor). In addition, it is known that the most severely affected patients (those who stay longer in hospital, who require intensive care, and who eventually die) are older people with pre-existing cardiovascular, metabolic, renal, and pulmonary diseases, the same people in which the prevalence of gut microflora dysbiosis is higher. The COVID-19 patients presenting poor outcomes are also those in which the immune system's hyperresponsiveness and a severe inflammatory condition (collectively referred as "cytokine storm") are particularly evident, and have been associated with impaired microbiota phenotype. In this article, we present the evidence existing thus far that may suggest an association between intestinal microbiota composition and the susceptibility of some patients to progress to severe stages of the disease.

Gut Microbiota Dysbiosis-Immune Hyperresponse-Inflammation Triad in Coronavirus Disease 2019 (COVID-19): Impact of Pharmacological and Nutraceutical Approaches.

Coronavirus Disease 2019 (COVID-19) is a pandemic infection caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients present a complex clinical picture that, in severe cases, evolves to respiratory, hepatic, gastrointestinal, and neurological complications, and eventually death. The underlying pathophysiological mechanisms are complex and multifactorial and have been summarized as a hyperresponse of the immune system that originates an inflammatory/cytokine storm. In elderly patients, particularly in those with pre-existing cardiovascular, metabolic, renal, and pulmonary disorders, the disease is particularly severe, causing prolonged hospitalization at intensive care units (ICU) and an increased mortality rate. Curiously, the same populations have been described as more prone to a gut microbiota (GM) dysbiosis profile. Intestinal microflora plays a major role in many metabolic and immune functions of the host, including to educate and strengthen the immune system to fight infections, namely of viral origin. Notably, recent studies suggest the existence of GM dysbiosis in COVID-19 patients. This review article highlights the interplay between the triad GM dysbiosis-immune hyperresponse-inflammation in the individual resilience/fragility to SARS-CoV-2 infection and presents the putative impact of pharmacological and nutraceutical approaches on the triumvirate, with focus on GM.

ACE2 imbalance as a key player for the poor outcomes in COVID-19 patients with age-related comorbidities - Role of gut microbiota dysbiosis.

Coronavirus disease 19 (COVID-19) is a pandemic condition caused by the new coronavirus SARS-CoV-2. The typical symptoms are fever, cough, shortness of breath, evolving to a clinical picture of pneumonia and, ultimately, death. Nausea and diarrhea are equally frequent, suggesting viral infection or transmission via the gastrointestinal-enteric system. SARS-CoV-2 infects human cells by using angiotensin converting enzyme 2 (ACE2) as a receptor, which is cleaved by transmembrane proteases during host cells infection, thus reducing its activities. ACE2 is a relevant player in the renin-angiotensin system (RAS), counterbalancing the deleterious effects of angiotensin II. Furthermore, intestinal ACE2 functions as a chaperone for the aminoacid transporter B0AT1. It has been suggested that B0AT1/ACE2 complex in the intestinal epithelium regulates gut microbiota (GM) composition and function, with important repercussions on local and systemic immune responses against pathogenic agents, namely virus. Notably, productive infection of SARS-CoV-2 in ACE2+ mature human enterocytes and patients' GM dysbiosis was recently demonstrated. This review outlines the evidence linking abnormal ACE2 functions with the poor outcomes (higher disease severity and mortality rate) in COVID-19 patients with pre-existing age-related comorbidities and addresses a possible role for GM dysbiosis. The article culminates with the therapeutics opportunities based on these pathways.