What Happens to Your Resident Gut E. coli when Disease-Causing E. coli Move In?

Aug. 3, 2018

E. coli maybe be associated with disease, but they are also an important component of the healthy human gut microbiome. Scientists used human volunteers to ask: what happens when resident, nonpathogenic E. coli meet pathogenic E.coli? Their results, in a new mSystems report, show a surprising resilience of the resident E. coli.

Although many associate Escherichia coli with disease (especially foodborne disease), most people have resident nonpathogenic E. coli as part of their healthy commensal gut microbiota. What happens to these resident E. coli when a pathogenic strain moves in? How do these resident E. coli recolonize after antibiotic treatment? A new mSystems study investigated these questions using human volunteers, and found a surprising resiliency that may lend insight into human health.

mSystems: Responses of the Human Gut Escherichia coli Population to Pathogen and Antibiotic Disturbances

If resident E. coli don’t cause disease, why should scientists spend time studying them? “I think it’s critical to look at the organisms that may be associated with a disease state as well as the residents,” said senior author Dave Rasko. “Right now, with current methods, many of these isolates are not well distinguished.” Rasko and first author Taylor Richter worked with a scientific team to characterize E. coli isolates using whole-genome sequencing. Their samples came from human volunteers taking part in an enterotoxogenic E. coli ETEC challenge study.

Richter and Rasko worked in collaboration with Wilbur Chen, who recruited the volunteers to participate in a human trial study lead at the Center for Vaccine Development at the University of Maryland. The volunteers drank an ETEC-laced glass of water after fasting (under clinical supervision, of course), and were treated with ciprofloxacin after 4 days or after losing 3 liters of stool, whichever came first. E. coli from volunteer stool was analyzed before and after drinking ETEC-laced water, and after antibiotic treatment with ciprofloxacin. 

2018.8.3 mSystemsSequences from isolates from each subject were compared with 32 previously sequenced E. coli and Shigella genomes and phylogenetic trees show the relatedness of these sequences (A) pre-ETEC ingestion, (B) after ETEC ingestion, and (C) after antibiotic treatment and disease resolution.. Source.

The E. coli isolates from healthy volunteers before ingesting ETEC were specific for each individual. The samples “were related, in that they were a similar phylogenetic clade when compared to other E. coli, but definitely unique,” said Rasko, who emphasized that the sample was unlikely to identify every E. coli isolate in each subject. These resident strains were part of phylogroup B2, which is not closely related to the challenge ETEC strain (see figure A).

After ingesting ETEC, these communities changed. 2 of the volunteers did not have the ETEC become the dominant species during challenge, and their resident E. coli remained phylogenetically distinct. The remaining volunteers became dominated by the ETEC, and their E. coli populations were indistinguishable (see figure B). ETEC takeover in the remaining patients occurred regardless of the severity of disease symptoms in patients; 5 of 6 volunteers who completed the study experienced some sort of diarrheal disease, with 2 mild, 1 moderate, and 2 severe cases.

Importantly, treatment with ciprofloxacin saw the E. coli return to its individual-specificity and most isolates returned to their individual-specific B2 phylogroup pattern (see figure C). Some of these populations returned even though they had been undetectable during the disease portion of the study. “For me, the most important finding was the resiliency of the resident E. coli,” said Rasko. “We are just starting to understand the dynamics of these organisms in association with our bodies. For many years, we’ve focused on the pathogens, but I think with the study of the microbiome and microbial systems, we will come to more fully appreciate the resident organisms that are present.”

Understanding resiliency is important because it may help guide treatment options in the future, said Rasko, who suggested these types of studies may help identify probiotic E. coli strains that are resistant to incoming pathogenic E. coli or could even displace the pathogens. These options will likely take a long time to develop, but this new mSystems study is a good starting point for understanding how resident and pathogenic E. coli interact in the human gut microbiome. 

E. coli SEM photo credit

Want more E. coli information?

Listen to an interview with Dave Rasko to hear more about using DNA sequencing to study enteric bacteria.

 


Author: Julie Wolf

Julie Wolf
Dr. Julie Wolf is in science communications at Indie Bio, and was a former ASM employee. Follow Julie on Twitter for more ASM and microbiology highlights at @JulieMarieWolf.