Authors: Sharon Salt, Future Science Group
A team of researchers have discovered that children with lower diversity of microbial species in their intestines may be more susceptible to severe infection with the Entamoeba histolytica parasite.The findings were recently published in PLOS Pathogens.
E. histolytica is a parasitic amoeba that causes amebic colitis, also known as amebiasis. Infection typically spreads through food, water or contact with contaminated feces with symptoms of the infection ranging from asymptomatic to life-threatening. The factors influencing severity remain unclear; however, previous studies have implicated the importance of the gut microbiome on E. histolytica virulence.
Researchers from the University of Virginia (VA, USA) and colleagues were able to analyze results from both human and animal data.
In the human investigation, they analyzed stool samples from children in an urban slum in Dhaka, Bangladesh. Their results displayed that children who experienced colon inflammation due to E. histolytica infection had a lower diversity of microbes in their stool in comparison with children who presented with asymptomatic infection.
To better understand their findings, the researchers then went on to investigate the effect of disrupting the gut microbiome in murine models by using antibiotics. The mice were then exposed to E. histolytica in order to examine their susceptibility to infection. Their results revealed that mice treated with antibiotics experienced more severe colon inflammation than untreated mice.
Within the study, the researchers stated that: “The most important finding of this study is that gut microbiome dysbiosis increases susceptibility to amebic colitis in humans and in the mouse model, and that one mechanism of this increased susceptibility is downregulated neutrophil recruitment to the gut.”
Gene expression analysis was able to reveal that on the surface of these neutrophils, the mice contained lower amounts of CXCR2 – a protein that plays a role in neutrophil recruitment to fight gut infections. Consequently, this lower CXCR2 expression on neutrophils likely resulted in “a susceptible phenotype to E. histolytica challenge in the antibiotic pre-treated mice.”
Additionally, disruption of the gut microbiome was also found to decrease the production of IL-25 – a protein that aids the function of the mucosal barrier, which is the intestine’s first line of defence against infection.
These findings suggest a molecular mechanism behind the disruption of the gut microbiome, which increases the severity of E. histolytica infection. However, as explained by the researchers: “Future work should assess dynamically the impact of antibiotic use on neutrophil function during amebic infection in a human cohort.”
The research concluded that: “Demonstration that antibiotics can impair neutrophil chemotaxis to a site of infection may be of broader importance than just amebiasis for the insight that it provides into gut microbiome regulation of the immune system.”
Sources: Watanabe K, Gilchrist CA, Uddin MJ et al. Microbiome-mediated neutrophil recruitment via CXCR2 and protection from amebic colitis. PLoS Pathog. 13(8), e1006513 (2017); www.sciencedaily.com/releases/2017/08/170817141819.htm