Phlorizin (PHZ) is one of the main pharmacologically
active ingredients
in Lithocarpus polystachyus. We have previously shown
that PHZ inhibits the replication of bovine viral diarrhea virus (BVDV),
but the exact antiviral mechanism, especially in vivo, is still unknown. Here, we further confirm that PHZ has good protective
effects in BVDV-infected mice. We analyzed BVDV-induced CD3+, CD4+, and CD8+ T cells among peripheral blood
lymphocytes and found that PHZ significantly restored their percentage.
Metagenomic analyses revealed that PHZ markedly improved the richness
and diversity of intestinal microbiota and increased the abundance
of potentially health-related microbes (families Lachnosipiraceae, Ruminococcaceae, and Oscillospiraceae). Specifically, the relative abundance of short chain fatty acid
(SCFA)-producing bacteria, including Lachnospiraceae_UCG-006, unclassified_f_Ruminococcaceae, Oscillibacter, Intestinimonas, Blautia, and Lachnoclostridium increased significantly after PHZ treatment.
Interestingly, BVDV-infected mice that received fecal microbiota from
PHZ-treated mice (PHZ-FMT) had a significantly lower viral load in
the duodenum and jejunum than untreated mice. Pathological lesions
of duodenum and jejunum were also greatly reduced in the PHZ-FMT group,
confirming a significant antiviral effect. These findings show that
gut microbiota play an important role in PHZ’s antiviral activity
and suggest that their targeted intervention might be a promising
endogenous strategy to prevent and control BVDV.