Microbiome Profiling of Enterotoxigenic Escherichia Coli (ETEC) Carriers Highlights Signature Differences Between Symptomatic and Asymptomatic Individuals

Abstract

BackgroundEscherichia coli (ETEC) are one of the top causes of diarrhoea in children in low- and middle-income countries (LMICs). However, large-scale pathogen burden studies in children have identified ETEC in the guts of symptomatic patients and controls. The factors that influence this balance between carriage and disease are poorly understood, but it is postulated that the gut microbiome may play a role in either resistance or progression to disease. In this study, we investigated the microbiome profiles, using shotgun DNA sequencing, of children and adults from Bangladesh who were asymptomatically or symptomatically infected with ETEC. ResultsSymptomatic patients had significantly higher numbers of sequenced reads mapping to both E. coli and the two ETEC toxins (LT and ST), suggesting higher bacterial burden. They were also significantly more likely to be co-infected with enteroaggregative E. coli (EAEC) and had higher proportions of other Gammaproteobacteria, including Klebsiella, Salmonella, and Haemophilus. Colonisation with ETEC (symptomatic or asymptomatic) was also associated with increased prevalence of antimicrobial resistance (AMR) genes, most notably those of the b-lactamase class. Taxonomic profiles were distinctly different between all groups in both species richness (alpha diversity) and composition (beta diversity), although the direction of these changes was different in adults and children. As seen in previous studies, children with high E. coli burdens also had higher proportions of Streptococcus spp., while healthy children were more heavily colonised by several Bifidobacterium spp. ConclusionsOur study provides insight into the microbiome changes that occur upon infection with ETEC in an endemic setting, and provides rationale for future studies investigating how the microbiome may protect or predispose individuals to symptomatic infections with gastrointestinal pathogens.

Protective effect of Limosilactobacillus reuteri‐fermented yogurt on mouse intestinal barrier injury induced by enterotoxigenic Escherichia coli

“…2 Among them, acute infectious diarrhea is a common cause of childhood mortality in developing countries, accounting for approximately 20% of all child deaths. 3 Furthermore, ETEC can induce intestinal microbiota disorder and destroy the integrity of the intestinal barrier by colonizing the small intestine and producing enterotoxin. 4 Enterotoxin and adhesion factors are two important virulence factors of ETEC.…”

“…Every year, approximately 400 million diarrhea cases are caused by ETEC infection worldwide 2 . Among them, acute infectious diarrhea is a common cause of childhood mortality in developing countries, accounting for approximately 20% of all child deaths 3 . Furthermore, ETEC can induce intestinal microbiota disorder and destroy the integrity of the intestinal barrier by colonizing the small intestine and producing enterotoxin 4 .…”