Intestinal permeability changes with bacterial translocation as key events modulating systemic host immune response to SARS-CoV-2: A working hypothesis

Abstract

The microbiota-gut-liver-lung axis plays a bidirectional role in the pathophysiology of a number of infectious diseases. During the course of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and 2 (SARS-CoV-2) infection, this pathway is unbalanced due to intestinal involvement and systemic inflammatory response. Moreover, there is convincing preliminary evidence linking microbiota-gut-liver axis perturbations, proinflammatory status, and endothelial damage in noncommunicable preventable diseases with coronavirus disease 2019 (Covid-19) severity. Intestinal damage due to SARS-CoV-2 infection, systemic inflammation-induced dysfunction, and IL-6-mediated diffuse vascular damage may increase intestinal permeability and precipitate bacterial translocation. The systemic release of damage- and pathogen-associated molecular patterns (e.g. lipopolysaccharides) and consequent immune-activation may in turn auto-fuel vicious cycles of systemic inflammation and tissue damage. Thus, intestinal bacterial translocation may play an additive/synergistic role in the cytokine release syndrome in Covid-19. This review provides evidence on gut-liver axis involvement in Covid-19 as well as insights into the hypothesis that intestinal endotheliitis and permeability changes with bacterial translocation are key pathophysiologic events modulating systemic inflammatory response. Moreover, it presents an overview of readily applicable measures for the modulation of the gut-liver axis and microbiota in clinical practice.

COVID-19 increased the risk of ICU-acquired bloodstream infections: a case–cohort study from the multicentric OUTCOMEREA network

“…First, SARS-CoV-2 may impair antigen presentation or trigger an acquired immunosuppression with concomitant lymphopenia, thus probably leading to an increased susceptibility to superinfection [ 25 , 26 ]. Second, the coagulopathy associated with SARS-CoV-2 may affect the micro- and macrocirculation [ 27 ], thus probably increasing the risk of bacterial translocation (e.g., in gastrointestinal tract) [ 28 ]. Moreover, endothelial dysfunctions of the digestive tract were frequently observed in COVID-19 and were associated with more mesenteric infarctions [ 29 ].…”

Factors associated with risk of COVID-19 contagion for endoscopy healthcare workers: A survey from the Italian society of digestive endoscopy

“…The capacity of the virus to survive in the gastrointestinal (GI) tract, to infect the intestinal epithelium [4 , 5] and its recovery in stools [6] led to the hypothesis that aerosols generated from the GI tract can transmit the infection [7] . In this view, digestive endoscopy examinations have been immediately considered high-risk procedures [8 , 9] due to the large viral loads in respiratory droplets, to aerosols generated by GI tract secretions including bile and stools and to the low physical distance between healthcare workers (HCWs) and patients during these procedures.…”

The Aging Bowel Dysfunction and Elderly Vulnerability towards COVID-19 Infection

“…Comparing Table 1 to Table 2 , one can see the similarity between the GI dysfunctions that are attributed to the aging process and those associated with SARC-Cov-2 infections. Interestingly, in both, digestion, absorption, mucosal barriers and immune dysfunctions, macrobiomic homeostasis, motility and gut permeability, and nutritional health are compromised [ 74 , 75 , 76 , 77 , 78 , 79 , 80 ]. More so, COVID-19–gut–aging relationships are further strengthened by the following observations.…”