Dynamics of the gut microbiome in subjects challenged with <i>Shigella sonnei</i> 53G in a controlled human infection modelOriginal paper
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease, four years before the first published case study.
Read MoreWhat was studied?
This study tracked how the gut microbiome changed when volunteers were deliberately infected with Shigella in a controlled human infection model. Researchers profiled fecal microbiomes by 16S rRNA sequencing before and during infection, after antibiotics, and after recovery. The design compared people who developed shigellosis, meaning severe symptoms like severe diarrhea, fever, or abdominal pain, against those who did not. The goal was to explain why some exposed people get sick while others stay asymptomatic, and to find microbiome features linked to protection or susceptibility.
Who was studied?
The study followed 45 adults infected with Shigella strain 53G in a controlled challenge trial registered as NCT02816346. Participants ranged across young and middle-aged adults and included both men and women. All were monitored longitudinally through infection, antibiotic treatment, and clinical recovery. This human challenge design let researchers observe the same individuals before and after a known exposure. Participants were classified by whether they progressed to shigellosis or avoided severe symptoms.
What were the most important findings?
Alpha diversity dropped more sharply in individuals who developed shigellosis. Shifts in microbial composition during infection and antibiotic treatment were significantly larger in the shigellosis group than in those without severe disease. People with shigellosis kept persistent microbiome changes after recovery, including taxa associated with gut inflammation. Those without shigellosis returned to a composition resembling their pre-infection state. Participants who avoided shigellosis started with a greater abundance of taxa tied to short-chain fatty acid production. This baseline difference distinguished those who would develop severe disease from those who would not.
What are the greatest implications of this study?
The results suggest the baseline microbiome may shape who develops severe Shigella disease, pointing to short-chain-fatty-acid-producing taxa as potential protective factors. This could inform preventive or microbiome-based strategies against diarrheal illness. Persistent post-recovery changes may help explain chronic sequelae after enteric infection, such as irritable bowel syndrome and altered gut permeability. The cohort was small and studied under controlled conditions, so associations do not prove that these taxa cause protection.