Prophylaxis of acute respiratory infections via improving the immune system in late preterm newborns with E. coli strain Nissle 1917: a controlled pilot trial

Abstract

BackgroundAcute respiratory infections (ARIs), caused by the high level of immaturity of the immune system, are a major cause of morbidity in preterm newborns. The probiotic Escherichia coli strain Nissle 1917 (EcN) is well known for its immuno-modulatory properties and may therefore enhance the immune competence. Thus, EcN administration may provide a promising possibility to decrease the risk of ARIs in this vulnerable group of children. However, clinical data supporting or refuting this hypothesis are, to our knowledge, not available. Therefore, the aim of the presented pilot trial was to collect first data on the efficacy and safety of EcN treatment to prevent ARIs in late preterm newborns.MethodsRight after birth, 62 late preterm newborns were included into an open-labeled, controlled 4-week trial with two parallel groups and a follow-up phase until the age of 1 year. All children of the treatment group received an EcN suspension orally for 3 weeks, whereas the control group was only observed. Primary efficacy variable was the number of participants with at least one ARI during the first 28 days of life. Secondary efficacy variables were the number of ARIs and the number and duration of hospitalizations caused by ARIs during the first year of life.ResultsThe number of participants with at least one ARI during the first 28 days of life was significantly lower in the group treated with EcN compared to that in the control group. Although only of exploratory nature, analyses of secondary efficacy variables suggest that EcN treatment may also reduce the average number of ARIs, the average number of hospitalizations caused by ARIs, and the mean duration of such hospitalizations. There is also some evidence that early EcN treatment may have long-term benefits on newborns’ health status.ConclusionThe present pilot trial provides first evidence that EcN is able to reduce the incidence of ARIs in the neonatal period of late preterm newborns. Additionally, EcN is characterized by an excellent individual biocompatibility in the absence of adverse drug reactions. Limitations of the current trial are discussed and recommendations for future confirmatory studies are made.Trial registrationClinicalTrials.gov identifier: NCT01540162; retrospectively registered on 16 February 2012

Potential Benefit of Probiotic E. Coli Nissle in Term Neonates

“…This was no longer observed at six or twelve months. There was a trend for fewer acute respiratory infections, of hospitalisations and shorter duration of these during the newborn period of up to 28 days, suggesting a more sustained beneficial effect of treatment [6]. E. coli Nissle 1917 may be effective against uropathogens [7] and antibiotic induced, rotavirus-associated gastroenteritis [8].…”

Oral Immunization with Escherichia coli Nissle 1917 Expressing SARS-CoV-2 Spike Protein Induces Mucosal and Systemic Antibody Responses in Mice

“…It has been demonstrated that EcN could trigger the production of anti-inflammatory mediators, such as IL-10, and suppress the immune response of lymphocyte T, macrophages, and other immunocompetent cells of both specific and nonspecific immunity, even at the systemic site [ 42 , 43 , 44 ]. In addition, EcN stimulated the systemic production of antibodies of B lymphocytes associated with the mucous membranes and induced the systemic production of antibodies (IgM, IgA) in adults [ 45 ]. The intestinal microenvironment and the engineered probiotic could, therefore, create a highly efficient and immunological-regulated antibody response on site [ 46 ].…”

Probiotics, Their Extracellular Vesicles and Infectious Diseases

“…As regards gastrointestinal diseases, probiotics were effective in reducing frequency and duration of diarrhea ( Francavilla et al, 2012 ; Park et al, 2017 ; Sharifi-Rad et al, 2020 ), reducing symptoms of gastroenteritis and H. pylori gastritis ( Shafaghi et al, 2016 ; Shin et al, 2020 ), and preventing necrotizing enterocolitis ( Chang et al, 2017 ). In respect of respiratory diseases, the benefit of probiotics has been mostly associated with prevention of infections, especially in the upper respiratory tract ( Aryayev et al, 2018 ; Anaya-Loyola et al, 2019 ; Lazou Ahrén et al, 2021 ). Finally, certain probiotics were successful in reducing symptoms and frequency of recurrent vulvovaginal candidiasis, bacterial vaginosis and urinary tract infections ( Laue et al, 2018 ; Russo et al, 2019 ; Sgibnev and Kremleva, 2020 ), possibly mainly by restoring the normal vaginal microbiota.…”