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Rotavirus (RV) infection is a major cause of acute gastroenteritis in children under 5 years old, resulting in elevated mortality rates in low-income countries. The efficacy of anti-RV vaccines is limited in underdeveloped countries, emphasizing the need for novel strategies to boost immunity and alleviate RV-induced diarrhea. This study explores the effectiveness of interventions involving extracellular vesicles (EVs) from probiotic and commensal E. coli in mitigating diarrhea and enhancing immunity in a preclinical model of RV infection in suckling rats. On days 8 and 16 of life, variables related to humoral and cellular immunity and intestinal function/architecture were assessed. Both interventions enhanced humoral (serum immunoglobulins) and cellular (splenic natural killer (NK), cytotoxic T (Tc) and positive T-cell receptor γδ (TCRγδ) cells) immunity against viral infections and downregulated the intestinal serotonin receptor-3 (HTR3). However, certain effects were strain-specific. EcoR12 EVs activated intestinal CD68 , TLR2 and IL-12 expression, whereas EcN EVs improved intestinal maturation, barrier properties (goblet cell numbers/mucin 2 expression) and absorptive function (villus length). In conclusion, interventions involving probiotic/microbiota EVs may serve as a safe postbiotic strategy to improve clinical symptoms and immune responses during RV infection in the neonatal period. Furthermore, they could be used as adjuvants to enhance the immunogenicity and efficacy of anti-RV vaccines.

Viral infections are described as modifying host gene expression; however, there is limited insight regarding rotavirus (RV) infections. This study aimed to assess the changes in intestinal gene expression after RV infection in a preclinical model, and the effect of 2-fucosyllactose (2'-FL) on this process. From days 2 to 8 of life, rats were supplemented with the dietary oligosaccharide 2'-FL or vehicle. In addition, an RV was inoculated on day 5 to nonsupplemented animals (RV group) and to 2'-FL-fed animals (RV+2'-FL group). Incidence and severity of diarrhea were established. A portion from the middle part of the small intestine was excised for gene expression analysis by microarray kit and qPCR. In nonsupplemented animals, RV-induced diarrhea upregulated host antiviral genes (e.g., Oas1a , Irf7 , Ifi44 , Isg15 ) and downregulated several genes involved in absorptive processes and intestinal maturation (e.g., Onecut2 , and Ccl19 ). The 2'-FL-supplemented and infected animals had less diarrhea; however, their gene expression was affected in a similar way as the control-infected animals, with the exception of some immunity/maturation markers that were differentially expressed (e.g., Ccl12 and Afp ). Overall, assessing the expression of these key genes may be useful in the evaluation of the efficacy of nutritional interventions or treatments for RV infection.

Rotavirus (RV) is the main cause of gastroenteritis in children. Prebiotics and, more recently, postbiotics are used for preventing and treating gastrointestinal infections. The aim of this study was to analyze the effects of a Lactofidus TM , short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharides (lcFOS) mixture, and their combination on RV infection, in a rat model, for early life diarrhea. Fifteen litters of suckling rats were intragastrically administered daily with the vehicle, the prebiotic mixture, the postbiotic or the combination. The RV was inoculated on day 5 and then fecal samples were clinically evaluated daily. Viral shedding, intestinal permeability assay, in vitro blocking assay, immunoglobulin profiles, and anti-RV response were assessed at day 8 and 16 of life. Cecal microbiota composition, intestinal gene expression, and short chain fatty acids (SCFAs) were analyzed at day 16. The incidence and severity of diarrhea were significantly reduced by all the supplementations. Moreover, they showed blocking activity, changes in the immunoglobulin profiles, in gut microbiota, and in the intestinal gene expression. The prebiotic mixture reduced gut permeability and changed the SCFA profile, whereas the postbiotic enhanced the expression of Toll-like receptors (TLRs). The combination preserved most of the individual observed effects, and furthermore, complementary effects, such as an increase in white blood cells and lymphocytes recruitment, as well as upregulation of TLR7 and TLR9 gene expression.

Probiotic supplementation with different lactobacilli and bifidobacterial strains has demonstrated beneficial effects in infectious diarrhea caused by rotavirus (RV) in young children. Preclinical models of RV infection might be a good strategy to screen for the efficacy of new probiotic strains or to test their comparative efficacy. Neonatal Lewis rats were supplemented with Bifidobacterium breve M-16V, Lactobacillus acidophilus NCFM, Lactobacillus helveticus R0052 , or Lactobacillus salivarius PS2 from days 2-14 of life. On day five, animals received RV SA-11 orally. Fecal samples were collected daily, weighed, and scored for the calculation of severity and incidence of diarrhea. In addition, fecal pH and fecal viral shedding were measured. Animals were sacrificed at the end of the study and their blood was obtained for the quantification of RV-specific immunoglobulins. RV infection was induced in ~90% of the animals. All probiotics caused a reduction of several clinical variables of severity and incidence of diarrhea, except L. salivarius PS2. L. acidophilus NCFM, B. breve M-16V, and L. helveticus R0052 seemed to be very effective probiotic strains. In addition, all Lactobacillus strains reduced the viral elimination one day post-inoculation. No differences were detected in the specific anti-RV humoral response. The present study highlights the strain-specific effects of probiotics and identifies promising probiotics for use in ameliorating and preventing RV-induced diarrhea in children, for example by including them in infant formulas.