Abstract
The effects of normal and altered intestinal microbiota on murine retroviral transmission via the gastrointestinal tract (GIT) are diverse. The role of orally administered antibiotic treatment (ABX) on viral transmission, GIT microbial dysbiosis and subsequent pathogenesis of Moloney Murine Leukemia virus-temperature sensitive 1 (ts1) on BALB/c mice were studied. BALB/c mice were divided into four groups: ABXts1-Treatment/Infection;ABX-Treatment/No infection;ts1-No treatment/Infection;Ctrl (control)-No treatment/No infection. ABXts1 and ABX groups showed a significant phylogenetic shift (ANOSIM p-value = 0.001) in alpha and beta diversity comparisons for microbial community composition compared to Ctrl group. Mice in the ABXts1 and ABX groups showed megacolon compared to ts1 and Ctrl groups; ABXts1 and ts1 groups showed hepatosplenomegaly, thymus enlargement, and mesenteric lymphadenopathy compared to ABX and Ctrl groups. Ctrl group had no abnormal manifestations. ABX treatment and ts1 infection uniquely affect microbial community when compared to control: ABXts1 and ABX groups significantly reduce microbiome diversity by over 80% and ts1 group by over 30%. ABXts1 and ts1 groups' viral load and clinical manifestations of infection were comparable; antibiotic treatment did not notably affect ts1 infection. Transmission and pathophysiology of ts1 infection were not significantly altered by the microbial composition of the GI tract, but ts1 viral infection did result in microbial dysbiosis independent of antibiotic treatment.
Highlights
The gastrointestinal tract (GIT) microbiota plays an integral and diverse role in health maintenance including metabolic, trophic and protective functions
We examined the effect of the microbiome on ts1 viral transmission, replication and pathological manifestations using the established ts1 murine model and previously validated oral antibiotic regimen (ABX) that alter murine GIT microbiome [7,8]
Oral antibiotic use has been shown to cause dysbiosis of GI microbiota by promoting disruption of resident bacteria leading to the emergence and expansion of non-resident pathogens with a rapid decrease in taxonomic richness, diversity and evenness of GI microbes [16,17,18,19,20]
Summary
The gastrointestinal tract (GIT) microbiota plays an integral and diverse role in health maintenance including metabolic, trophic and protective functions. The intact gut microbiome has been found to be a necessary component for the establishment of infection for certain retroviruses, such as the mouse mammary tumor virus (MMTV). In this model, antibiotic-treated mice do not transmit virus to their offspring via ingestion of MMTV-laden breast milk, and dysbiosis becomes protective [7]. The ts model was uniquely suited for this study since transmission of this retrovirus occurs post-partum through the GIT from oral ingestion of infected breast milk and results in reproducible clinical symptoms, including splenic neoplasm [9]. Comparisons were made between these groups to examine the effects of antibiotic treatment on ts viral transmission, pathological manifestations and microbiome diversity
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