Differential Response of the Cynomolgus Macaque Gut Microbiota to Shigella Infection

Abstract

Little is known about the role of gut microbiota in response to live oral vaccines against enteric pathogens. We examined the effect of immunization with an oral live-attenuated Shigella dysenteriae 1 vaccine and challenge with wild-type S. dysenteriae 1 on the fecal microbiota of cynomolgus macaques using 16 S rRNA analysis of fecal samples. Multi-dimensional cluster analysis identified different bacterial community types within macaques from geographically distinct locations. The fecal microbiota of Mauritian macaques, observed to be genetically distinct, harbored a high-diversity community and responded differently to Shigella immunization, as well as challenge compared to the microbiota in non-Mauritian macaques. While both macaque populations exhibited anti-Shigella antibody responses, clinical shigellosis was observed only among non-Mauritian macaques. These studies highlight the importance of further investigation into the possible protective role of the microbiota against enteric pathogens and consideration of host genetic backgrounds in conducting vaccine studies.

Microbial Translocation and Inflammation Occur in Hyperacute Immunodeficiency Virus Infection and Compromise Host Control of Virus Replication

“…Although Ruminococcus , Oscillospira , and Lactobacillus are known constituents of cynomolgus macaque flora[14], Cloacibacterium and Limnohabitans are not often observed in vertebrates. However, Cloacibacterium has been observed in the gastrointestinal tract of patients with adenomas[15], and Limnohabitans has been observed in patients with cellulitis[16] .…”

Homeostatic Immunity and the Microbiota

“…Recent studies have suggested that the gut microbiota could influence vaccine efficacy in human and non-human primates (Valdez et al, 2014). For instance, a study using Cynomolgus macaques supports the idea that a stable and more diverse gut microbiota correlates with a better response to vaccination and subsequent immunity (Seekatz et al, 2013). This finding is consistent with another study involving a small human cohort, in which the majority of individuals that responded to vaccination had greater community richness and diversity amongst their gut microbiota (Eloe-Fadrosh et al, 2013).…”

Influence of the microbiota on vaccine effectiveness

“…In a related study by the same group, Macaques of different geographic origins (with distinct genetic makeup and a different MHC allele repertoire) were immunized with two live attenuated Shigella disenteriae (S. dysenteriae) vaccine candidates [84]. Protection was evaluated by response to subsequent challenge with wild type S. dysenteriae.…”