Abstract

BackgroundHuman rotavirus (HRV) is a major cause of viral gastroenteritis in infants; particularly in developing countries where malnutrition is prevalent. Malnutrition perturbs the infant gut microbiota leading to sub-optimal functioning of the immune system and further predisposing infants to enteric infections. Therefore, we hypothesized that malnutrition exacerbates rotavirus disease severity in infants.MethodsIn the present study, we used a neonatal germ free (GF) piglets transplanted with a two-month-old human infant’s fecal microbiota (HIFM) on protein deficient and sufficient diets. We report the effects of malnourishment on the HRV infection and the HIFM pig microbiota in feces, intestinal and systemic tissues, using MiSeq 16S gene sequencing (V4-V5 region).ResultsMicrobiota analysis indicated that the HIFM transplantation resulted in a microbial composition in pigs similar to that of the original infant feces. This model was then used to understand the interconnections between microbiota diversity, diet, and HRV infection. Post HRV infection, HIFM pigs on the deficient diet had lower body weights, developed more severe diarrhea and increased virus shedding compared to HIFM pigs on sufficient diet. However, HRV induced diarrhea and shedding was more pronounced in non-colonized GF pigs compared to HIFM pigs on either sufficient or deficient diet, suggesting that the microbiota alone moderated HRV infection. HRV infected pigs on sufficient diet showed increased microbiota diversity in intestinal tissues; whereas, greater diversity was observed in systemic tissues of HRV infected pigs fed with deficient diet.ConclusionsThese results suggest that proper nourishment improves the microbiota quality in the intestines, alleviates HRV disease and lower probability of systemic translocation of potential opportunistic pathogens/pathobionts. In conclusion, our findings further support the role for microbiota and proper nutrition in limiting enteric diseases.

Highlights

  • Human rotavirus (HRV) is a major cause of viral gastroenteritis in infants; in developing countries where malnutrition is prevalent

  • Though our results clearly demonstrate the interconnections between the diet, microbiota and HRV infection, it should be taken into consideration that only limited number of pigs was used in each treatment group in this study due to the complex nature of experiments with the germ free (GF) animals

  • In the present study, we showed that HRV infected malnourished human infant’s fecal microbiota (HIFM) piglets had perturbed gut microbiota and recapitulated the clinical signs read as seen in malnourished HRV infected infants

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Summary

Introduction

Human rotavirus (HRV) is a major cause of viral gastroenteritis in infants; in developing countries where malnutrition is prevalent. Malnutrition perturbs the infant gut microbiota leading to sub-optimal functioning of the immune system and further predisposing infants to enteric infections. Kumar et al BMC Gastroenterology (2018) 18:93 and enteric diseases form a vicious cycle because enteric diseases are more likely to occur in a malnourished host, and enteric pathogens aggravate malnutrition symptoms. This vicious cycle is difficult to overcome without proper intervention [8, 9]. Malnutrition results in intestinal dysbiosis, sub-optimal immune function, and increased gut permeability leading to a higher probability of translocation of opportunistic pathogenic bacteria or pathobionts and secondary infections [8, 9]. The role of the gut microbiota is increasingly recognized in health and disease

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