Oligosaccharides Modulate Rotavirus-Associated Dysbiosis and TLR Gene Expression in Neonatal Rats.

Ignasi Azagra-Boronat,Karen Knipping,Jan Knol,Belinda Van‘T Land,Margarida Castell,Johan Garssen,Sebastian Tims,Malén Massot-Cladera,Bernd Stahl,Maria J Rodríguez-Lagunas,Àngels Franch,Francisco J Pérez-Cano

doi:10.3390/cells8080876

Abstract

Colonization of the gut in early life can be altered through multiple environmental factors. The present study aimed to investigate the effects of 2’-fucosyllactose (2’-FL), a mixture of short-chain galactooligosaccharides/long-chain fructooligosaccharides (scGOS/lcFOS) 9:1 and their combination (scGOS/lcFOS/2’-FL) on dysbiosis induced during rotavirus (RV) diarrhea in neonatal rats, elucidating crosstalk between bacteria and the immune system. The dietary interventions were administered daily by oral gavage at days 2–8 of life in neonatal Lewis rats. On day 5, RV SA11 was intragastrically delivered to induce infection and diarrhea assessment, microbiota composition, and gene expression of Toll-like receptors (TLRs) in the small intestine were studied. All dietary interventions showed reduction in clinical variables of RV-induced diarrhea. RV infection increased TLR2 expression, whereas 2’-FL boosted TLR5 and TLR7 expressions and scGOS/lcFOS increased that of TLR9. RV-infected rats displayed an intestinal dysbiosis that was effectively prevented by the dietary interventions, and consequently, their microbiota was more similar to microbiota of the noninfected groups. The preventive effect of 2’-FL, scGOS/lcFOS, and their combination on dysbiosis associated to RV diarrhea in rats could be due to changes in the crosstalk between gut microbiota and the innate immune system.

Highlights

Microbial colonization is crucial for early life development of the gut by inducing maturation of the intestinal epithelium and gut-associated immune system [1]
The microbial sensing through pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) or Nod-like receptors (NLRs) is suggested to influence microbial colonization and correct immune development [2,4]
We aimed to investigate the effects of 2’-FL, short-chain galactooligosaccharides (scGOS)/long-chain fructooligosaccharides (lcFOS), and their combination on the dysbiosis caused by RV diarrhea in neonatal rats

Summary

Introduction

Microbial colonization is crucial for early life development of the gut by inducing maturation of the intestinal epithelium and gut-associated immune system [1]. The composition of commensal microorganisms, known as microbiota, is subject to dietary and environmental changes, driving the microbial ecosystem to adapt both qualitatively and quantitatively [2]. There is a balance in the gut microbiota, creating a homeostatic state inside the gastrointestinal tract which allows for a correctly functioning gut and limits overgrowth of potentially pathogenic microorganisms. Cells 2019, 8, 876 metabolic activities [1]. PRRs play an essential role in the innate immune system by recognizing microbe-specific and damage-associated molecules, by triggering host defensive responses, and by providing protection from invading intestinal pathogens.

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