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Amebic Infection Severity May Decline as Gut Microbial Diversity Increases

NEW YORK (GenomeWeb) – Researchers from the US, Japan, and Bangladesh have identified gut microbial community shifts in children who are prone to severe cases of amebic dysentery caused by Entamoeba histolytica infections.

The investigators used 16S ribosomal RNA sequencing on stool samples from dozens of children from birth cohorts in Dhaka, Bangladesh to tally up and compare gut microbial diversity in children without E. histolytica infections, with asymptomatic E. histolytica infections, and in those with serious complications such as amebic colitis.

Their results, published online today in PLOS Pathogens, pointed to declining microbial diversity as an E. histolytica infection bellwether, while the presence of more diverse microbes in the gut appeared to protect against amebic colitis. Following a series of follow-up studies in mice, they suggested that this effect may be due to gut microbe influence on immune cell recruitment to infection sites.

"In children who developed symptomatic colitis by E. histolytica, the gut microbiota had lower diversity than those in children who showed colonization," senior author William Petri, an infectious diseases and international health researcher at the University of Virginia, and his colleagues wrote. "Moreover, we found that children developing amebic colitis had lower microbiome diversity in the month preceding amebic colitis than those without E. histolytica infection, although these data came from [two] different cohort studies at the same location."

The researchers began by looking at the microbial diversity in stool samples from 20 children with amebic colitis who were enrolled through the "Performance of Rotavirus and Polio Vaccines in Developing Countries," or PROVIDE birth cohort in Dhaka, and 47 children from a National Institutes of Health birth cohort in the same city.

Based on their 16S rRNA sequence data, the investigators saw signs of declining microbial diversity in children with symptomatic E. histolytica infections relative to children who were colonized by the bug but did not have obvious symptoms. The team also noted that children who developed amebic colitis had lower gut microbial diversity at baseline in pre-infection stool samples compared with children who remained uninfected or who had asymptomatic infections.  

To explore these findings in more detail, the researchers turned to mouse models of amebic colitis, where they found further support for the role of the gut microbe in amebic dysentery infection severity. In mice that downed multiple antibiotics before exposure to E. histolytica, for example, microbial diversity declined and symptoms of the amebic infections became more severe.

With a series of imaging, histopathology, expression, and other experiments in antibiotic-treated or -untreated mice, the team came up with a model suggesting E. histolytica infections may become more severe as gut microbiome dysbiosis upends expression of a neutrophil chemoattractant cytokine that would normally attract immune cells to infection sites in the gut.

The authors noted that such findings may have implications for locales affected by amebic infections, since "[a]ntibiotic use is pervasive in children in low- and middle-income countries and a likely cause of dysbiosis."