Rotavirus infection induces glycan availability to promote ileum-specific changes in the microbiome aiding rotavirus virulence

Abstract

Multiple studies have identified changes within the gut microbiome in response to diarrheal-inducing bacterial pathogens. However, examination of the microbiome in response to viral pathogens remains understudied. Compounding this, many studies use fecal samples to assess microbiome composition; which may not accurately mirror changes within the small intestine, the primary site for most enteric virus infections. As a result, the functional significance of small intestinal microbiome shifts during infection is not well defined. To address these gaps, rotavirus-infected neonatal mice were examined for changes in bacterial community dynamics, host gene expression, and tissue recovery during infection. Profiling bacterial communities using 16S rRNA sequencing suggested significant and distinct changes in ileal communities in response to rotavirus infection, with no significant changes for other gastrointestinal (GI) compartments. At 1-d post-infection, we observed a loss in Lactobacillus species from the ileum, but an increase in Bacteroides and Akkermansia, both of which exhibit mucin-digesting capabilities. Concomitant with the bacterial community shifts, we observed a loss of mucin-filled goblet cells in the small intestine at d 1, with recovery occurring by d 3. Rotavirus infection of mucin-producing cell lines and human intestinal enteroids (HIEs) stimulated release of stored mucin granules, similar to in vivo findings. In vitro, incubation of mucins with Bacteroides or Akkermansia members resulted in significant glycan degradation, which altered the binding capacity of rotavirus in silico and in vitro. Taken together, these data suggest that the response to and recovery from rotavirus-diarrhea is unique between subcompartments of the GI tract and may be influenced by mucin-degrading microbes.

Microbiome profiling of rotavirus infected children suffering from acute gastroenteritis

“…An increase in alpha diversity relative to healthy controls was observed in the RV infected children. This observation contradicts previous studies, which recorded a decrease [ 14 , 15 , 18 ] or no effect on alpha diversity [ 19 ]. However, the increase in alpha diversity in the infected population could be due to the non-convergence of the family Enterobacteriaceae , which accounted for about 16 % and could not be further resolved at the level of genus/species.…”

“…The authors observed an increase in the abundance of Proteobacteria in RV infected children compared to the controls. More recently, Engevik et al [ 15 ] showed that RV infectivity and virulence are dependent on microbiome changes, particularly by elevated Proteobacteria and a decrease in abundance of Firmicutes. Gram-negative bacteria, especially Proteobacteria and Fusobacteria, can interfere with specific innate immune responses and cause severe gastritis expressing flagella or toxigenic lipopolysaccharides (LPS) [ 16 ].…”

The Complex Interactions Between Rotavirus and the Gut Microbiota

“…MRV infection causes significant changes to the composition of the ileal microbiota by inducing mucin secretion from goblet cells ( Engevik et al., 2020 ). This compositional shift favors mucin-degrading bacteria Bacteroides and Akkermansia , which in turn could also promote mRV infection in vitro .…”

Interaction of intestinal bacteria with human rotavirus during infection in children

“…Infection by RV produces a shift in nutrient availability in the gut and induces goblet cells to release mucin, which promotes growth of mucin-degraders Bacteroides and Akkermansia members in mice ileum. Consumption of mucin by these bacteria may, in turn, decrease the protection exerted by mucin against RV infection [37]. It is not known at this stage whether high Ruminococcus levels would represent a protective factor against RV infection in children and, in fact, samples where Ruminococcus were detected derived from children suffering diarrhea.…”