BACTERIAL TRANSLOCATION: MICROBIOTA-INTESTINE-LUNG AXIS AND PRO-INFLAMMATORY STATUS IN THE SEVERITY OF COVID-19

Although severe acute respiratory syndrome coronavirus – 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19) pandemic, is primarily associated with a respiratory infection, it has also been linked to multisystem involvement that includes the digestive tract. Gastrointestinal (GI) manifestations are common in patients with COVID-19 due to the high viral load lodged in the small intestine's mucosa. As a result, it causes an increase in the permeability of the intestinal barrier that favours the passage and translocation of bacteria, from the lumen of the intestine, towards the internal environment, with the appearance of sepsis, with evidence that SARS-CoV-2 has been found in faeces. This article highlights epidemiology, clinical symptoms, and mechanisms related to manifestations of disease in the GI tract and its pathogenesis in patients with COVID-19. It highlights bacterial translocation and COVID-19, mechanisms that control bacterial translocation, intestinal infection and feco-oral transmission, defense

The Gut and Blood Microbiome in IgA Nephropathy and Healthy Controls

Background: IgA nephropathy (IgAN) has been associated with gut dysbiosis, intestinal membrane disruption and translocation of bacteria into blood. Our study aimed to understand the association of gut and blood microbiomes in IgAN patients in relation to healthy controls. Methods: We conducted a case control study with 20 progressive IgAN patients matched with 20 healthy controls, analyzing bacterial DNA quantitatively in blood by 16S PCR and qualitatively in blood and stool by 16S metagenomic sequencing. Between group comparisons as well as comparisons between the blood and gut microbiomes were conducted. Results: Higher median 16S bacterial DNA in blood was found in the IgAN group compared to the healthy controls group (7410 vs 6030 16SrDNA copies/uL blood, p = 0.04). Alpha and beta diversity in both blood and stool was largely similar between the IgAN and healthy groups.. Higher proportions of class Coriobacteriia, and species of genera legionella, Enhydrobacter and parabacteroides in blood; and species of genera Bacteroides, Escherichia-Shigella and some Ruminococcus in stool were observed in IgAN patients in comparison with healthy controls. Taxa distribution were markedly different between the blood and stool samples of each subject in both IgAN and healthy groups without any significant correlation between corresponding gut and blood phyla. Conclusions: Important bacterial taxonomic differences quantitatively in blood and qualitatively in both blood and stool samples detected between IgAN and healthy groups warrant further investigation into their roles in the pathogenesis of IgAN. While gut bacterial translocation into blood may be one of the potential sources of the blood microbiome, marked taxonomic differences between gut and blood samples in each subject in both groups confirms that the blood microbiome does not directly reflect the gut microbiome. Further research is needed into other possible sites of origin and internal regulation of the blood microbiome.

727. Outcomes of Antibiotic Use in Ischemic Colitis

Background Ischemic colitis (IC) is caused by inadequate blood flow to the colon. Most cases resolve with conservative management. Isolated right-sided colitis, peritonitis, shock, and vascular risk factors are predictors of severe disease which can be life-threatening and require surgery. Current guidelines recommend antibiotics for moderate/severe disease. This is based on results from animal models and concern for gut translocation of bacteria; there have been no comparative studies in humans. This study aims to evaluate whether there is benefit to antibiotic use in non-severe IC. Methods This is a single-center retrospective cohort study of adult patients hospitalized with IC from 2015-2018. Inclusion in the study required endoscopic, radiologic, operative, or histologic evidence of ischemic colitis. Patients were divided into mild/moderate and severe IC cohorts as per 2014 American College of Gastroenterology Guidelines. Primary outcomes were length of stay (LOS) and any adverse event, which is defined as a composite measure of pre-specified secondary outcomes including mortality, need for surgery, 1-year relapse, and bacteremia. Results Of 191 patients enrolled in the study, 130 had mild/moderate IC and 61 had severe IC. In mild/moderate IC groups there was no significant difference in total adverse events, although use of antibiotics was associated with a significant increase in LOS (Table 1). In the severe IC groups there was no significant difference in any primary outcomes, but mortality was lower at 3 and 6 months among patients who did not receive antibiotics. Table 1 Conclusion Antibiotics did not improve outcomes in mild/moderate IC, suggesting that conservative management may be sufficient in this group. Antibiotic use was associated with increased LOS in mild/moderate IC and with increased mortality in severe IC; it is not clear whether these associations are true antibiotic-mediated adverse effects or whether they simply reflect a tendency to use antibiotics more frequently in patients who are more unstable. Future prospective research is needed to establish clear guidelines for antibiotic indications, agent selection, and optimal treatment duration. Disclosures All Authors: No reported disclosures

ABOUT TRANSLOCATION OF BACTERIA IN PRACTICALLY HEALTHY PEOPLE

At research of blood plasma by scanning electronic microscopy in group of 67 practically healthy inhabitants of Blagoveshchensk in 77.6% of cases asymptomatic bacteremia, i.e. translocation of elementary bodies of L-forms bacteria was found out and only in 22.4% of the citizens it was not visualized. The same changes were also revealed in 2 practically healthy gold miners working in difficult environment. Presumably, the translocation of elementary bodies of bacteria occurs owing to the moderate infringement of microbic landscape of thick intestines and insignificant dysfunction of intestines barriers, and it inherently proves poor health of respondents.

Role of hepatic macrophages in alcoholic liver disease

Alcohol consumption can lead to the increase in gut permeability and cause the translocation of bacteria-derived lipopolysaccharides from the gut to the liver, which subsequently activates immune responses. In this process, macrophages play a critical role and involve in the pathogenesis of alcoholic liver disease (ALD). To define the mechanism underpinning the function of macrophages, it is important to conduct extensive studies to further explicate the phenotypic diversity of macrophages in the context of ALD. In this review, the role of hepatic macrophages in the pathogenesis of ALD is discussed.

Gut microbiota translocation to the pancreatic lymph nodes triggers NOD2 activation and contributes to T1D onset

Type 1 diabetes (T1D) is an autoimmune disease that is triggered by both genetic and environmental factors, resulting in the destruction of pancreatic β cells. The disruption of the intestinal epithelial barrier and consequent escape of microbial products may be one of these environmental triggers. However, the immune receptors that are activated in this context remain elusive. We show here that during streptozotocin (STZ)-induced T1D, the nucleotide-binding oligomerization domain containing 2 (NOD2), but not NOD1, participates in the pathogenesis of the disease by inducing T helper 1 (Th1) and Th17 cells in the pancreatic LNs (PLNs) and pancreas. Additionally, STZ-injected wild-type (WT) diabetic mice displayed an altered gut microbiota compared with vehicle-injected WT mice, together with the translocation of bacteria to the PLNs. Interestingly, WT mice treated with broad-spectrum antibiotics (Abx) were fully protected from STZ-induced T1D, which correlated with the abrogation of bacterial translocation to the PLNs. Notably, when Abx-treated STZ-injected WT mice received the NOD2 ligand muramyl dipeptide, both hyperglycemia and the proinflammatory immune response were restored. Our results demonstrate that the recognition of bacterial products by NOD2 inside the PLNs contributes to T1D development, establishing a new putative target for intervention during the early stages of the disease.