Liechty Zachary, Baldwin Arianna, Isidean Sandra, Suvarnapunya Akamol, Frenck Robert, Porter Chad, Goodson Michael
711th Human Performance Wing, Air Force Research Laboratory, Wright-Patterson Air Force Base, Dayton, Ohio, USA.
Health and Performance Technologies Division, Blue Halo, Inc., Dayton, Ohio, USA.
mSphere. 2025 Apr 29;10(4):e0090624. doi: 10.1128/msphere.00906-24. Epub 2025 Mar 28.
is a significant cause of diarrhea, predominantly affecting children in low- and middle-income countries, as well as international travelers. Not all individuals exposed to or other enteropathogens have symptomatic responses, and investigating the differences between symptomatic and asymptomatic individuals can further our understanding of enteropathogen proliferation and symptomatic responses. Here, we profiled the fecal microbiomes of 45 individuals infected with strain 53G through 16S rRNA sequencing in a controlled human infection model before and during infection, after antibiotic treatment, and after clinical recovery. This model allowed for a detailed exploration of microbiome temporal dynamics during infection, as well as a comparative analysis between those with shigellosis (defined as severe symptoms caused by infection, including severe diarrhea, fever, and/or abdominal pain) and those without shigellosis. Alpha diversity decreased to a greater degree in individuals with shigellosis. Perturbations in microbial composition during infection and antibiotic treatment were significantly larger in individuals diagnosed with shigellosis than in those who were not. Participants with shigellosis had persistent changes to their microbiomes after recovery, while those without shigellosis recovered to a composition resembling their pre-infection microbiomes. These persistent changes included taxa associated with gut inflammation, such as a decrease in and an increase in . Furthermore, the initial microbiomes of participants who did not develop shigellosis had a greater abundance of taxa associated with short-chain fatty acid production than participants who did develop shigellosis, including , , and . These data could help prevent infection or symptoms.IMPORTANCEDiarrheal disease is a major contributor to the global disease burden and can lead to an increased individual risk of chronic sequelae post-infection, such as irritable bowel syndrome, reactive arthritis, and altered gut permeability. Understanding the differential responses of individuals to enteropathogen exposure can elucidate factors that could lead to treatments or preventative measures to reduce the disease burden. Here, we use a controlled human infection model study to directly identify the effects of 53G infection on the microbiome. We identified taxa that were more or less abundant in participants who would develop shigellosis during the study, as well as persistent changes after recovery in the microbiomes of participants who developed severe symptoms. Understanding these changes could elucidate ways to prevent infection or recover altered microbiomes after recovery.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT02816346.
是腹泻的一个重要原因，主要影响低收入和中等收入国家的儿童以及国际旅行者。并非所有接触[病原体名称未给出]或其他肠道病原体的个体都会出现症状反应，研究有症状和无症状个体之间的差异可以加深我们对肠道病原体增殖和症状反应的理解。在这里，我们通过16S rRNA测序，在一个受控的人类感染模型中，对45名感染了53G菌株的个体在感染前、感染期间、抗生素治疗后以及临床康复后的粪便微生物群进行了分析。这个模型允许详细探索感染期间微生物群的时间动态，以及对患有志贺氏菌病（定义为由[病原体名称未给出]感染引起的严重症状，包括严重腹泻、发烧和/或腹痛）的个体和没有志贺氏菌病的个体进行比较分析。患有志贺氏菌病的个体中，α多样性下降的程度更大。在感染和抗生素治疗期间，被诊断患有志贺氏菌病的个体的微生物组成扰动明显大于未患该病的个体。患有志贺氏菌病的参与者在康复后其微生物群有持续变化，而没有志贺氏菌病的参与者则恢复到类似于感染前微生物群的组成。这些持续变化包括与肠道炎症相关的分类群，如[分类群名称未给出]减少和[分类群名称未给出]增加。此外，未患志贺氏菌病的参与者初始微生物群中与短链脂肪酸产生相关的分类群丰度高于患志贺氏菌病的参与者，包括[分类群名称未给出]、[分类群名称未给出]和[分类群名称未给出]。这些数据有助于预防[病原体名称未给出]感染或症状。重要性腹泻病是全球疾病负担的主要贡献者，可导致个体感染后慢性后遗症风险增加，如肠易激综合征、反应性关节炎和肠道通透性改变。了解个体对肠道病原体暴露的不同反应可以阐明可能导致治疗或预防措施以减轻疾病负担的因素。在这里，我们使用一个受控的人类感染模型研究来直接确定53G感染对微生物群的影响。我们确定了在研究期间会患志贺氏菌病的参与者中丰度较高或较低的分类群，以及出现严重症状的参与者康复后微生物群的持续变化。了解这些变化可以阐明预防[病原体名称未给出]感染或康复后恢复改变的微生物群的方法。临床试验本研究已在ClinicalTrials.gov注册，注册号为NCT02816346。
