Abstract
The effects of co-colonization with Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (Bb12) on 3-dose vaccination with attenuated HRV and challenge with virulent human rotavirus (VirHRV) were assessed in 4 groups of gnotobiotic (Gn) pigs: Pro+Vac (probiotic-colonized/vaccinated), Vac (vaccinated), Pro (probiotic-colonized, non-vaccinated) and Control (non-colonized, non-vaccinated). Subsets of pigs were euthanized pre- [post-challenge day (PCD) 0] and post (PCD7)-VirHRV challenge to assess diarrhea, fecal HRV shedding and dendritic cell/innate immune responses. Post-challenge, Pro+Vac and Vac groups were completely protected from diarrhea; protection rates against HRV shedding were 100% and 83%, respectively. Diarrhea and HRV shedding were reduced in Pro compared to Control pigs following VirHRV challenge. Diarrhea scores and virus shedding were significantly higher in Controls, compared to all other groups, coincident with significantly higher serum interferon-alpha levels post-challenge. LGG+Bb12 colonization ±vaccine promoted immunomaturation as reflected by increased frequencies of CD4, SWC3a, CD11R1, MHCII expressing mononuclear cells (MNCs) and conventional dendritic cells in intestinal tissues and blood post-challenge. Colonization decreased frequencies of toll-like receptors (TLR) 2 and TLR4 expressing MNCs from vaccinated pigs (Pro+Vac) pre-challenge and increased frequencies of TLR3 expressing MNCs from Pro pigs post-challenge, suggesting that probiotics likely exert anti-inflammatory (TLR2 and 4 down-regulation) and antiviral (TLR3 up-regulation by HRV dsRNA) actions via TLR signaling. Probiotic colonization alone (Pro) increased frequencies of intestinal and systemic apoptotic MNCs pre-challenge, thereby regulating immune hyperreactivity and tolerance. However, these frequencies were decreased in intestinal and systemic tissues post-challenge, moderating HRV-induced apoptosis. Additionally, post-challenge, Pro+Vac and Pro groups had significantly decreased MNC proliferation, suggesting that probiotics control excessive lymphoproliferative reactions upon VirHRV challenge. We conclude that in the neonatal Gn pig disease model, selected probiotics contribute to immunomaturation, regulate immune homeostasis and modulate vaccine and virulent HRV effects, thereby moderating HRV diarrhea.
Highlights
The human gastrointestinal tract, inhabited by over 1,000 species of microorganisms, has a very high level of metabolic and immune activities [1] and sustains the balance between immunity and tolerance
In this study we evaluated the impact of co-colonization by Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (Bb12), two commensals selected because they are dominant in breast-fed infants, on human rotavirus (HRV) diarrhea, development of innate immune responses and vaccine efficacy using a neonatal Gn pig model of HRV vaccination and infection
(at PID0), total fecal bacteria shedding was similar between both colonized groups (Pro+Vac and Probiotic colonization alone (Pro)) but postvaccination, at PID2 it was lower and after PID8: from 6.581E+05 CFU/ml (at PID8) it was significantly lower in the Pro group
Summary
The human gastrointestinal tract, inhabited by over 1,000 species of microorganisms, has a very high level of metabolic and immune activities [1] and sustains the balance between immunity and tolerance. Butler et al using Gn pigs further demonstrated stimulatory effects of commensal microflora on differentiation of naive B cells into plasma cells and/or expression of costimulatory molecules (for T and B cells) by antigen presenting cells [9] They showed that the commensal microflora stimulates antibody production to non-bacterial T cell dependent and independent antigens and plays a major role in the overall development of the systemic and mucosal immune systems of the neonate [9]. Another study demonstrated that conventional bacteria and E. coli but not L. fermentum increased overall enterocyte turnover through stimulating apoptosis and cell proliferation [13] These findings using Gn animals support the hypothesis that postnatal bacterial colonization patterns have a profound and multifaceted effect on development of the neonatal immune system
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
