Antibiotic usage promotes intestinal colonization of antibiotic-resistant bacteria. However, whether resistant bacteria gain dominance in enteric microflora or disseminate to extraintestinal viscera remains unclear. Our aim was to investigate temporal diversity changes in microbiota and transepithelial routes of bacterial translocation after antibiotic-resistant enterobacterial colonization. Mice drinking water with or without antibiotics were intragastrically gavaged with ampicillin-resistant (Amp-r) nonpathogenic Escherichia coli (E. coli) and given normal water afterward. The composition and spatial distribution of intestinal bacteria were evaluated using 16S rDNA sequencing and fluorescence in situ hybridization. Bacterial endocytosis in epithelial cells was examined using gentamicin resistance assay and transmission electromicroscopy. Paracellular permeability was assessed by tight junctional immunostaining and measured by tissue conductance and luminal-to-serosal dextran fluxes. Our results showed that antibiotic treatment enabled intestinal colonization and transient dominance of orally acquired Amp-r E. coli in mice. The colonized Amp-r E. coli peaked on day 3 postinoculation and was competed out after 1 wk, as evidenced by the recovery of commensals, such as Escherichia, Bacteroides, Lachnospiraceae, Clostridium, and Lactobacillus. Mucosal penetration and extraintestinal dissemination of exogenous and endogenous enterobacteria were correlated with abnormal epithelial transcytosis but uncoupled with paracellular tight junctional damage. In conclusion, antibiotic-induced enteric dysbiosis predisposes to exogenous infection and causes systemic dissemination of both antibiotic-resistant and commensal enterobacteria through transcytotic routes across epithelial layers. These results may help explain the susceptibility to sepsis in antibiotic-resistant enteric bacterial infection.
ObjectiveTo explore the relationships between swallowing functional outcomes and nutritional status in patients with head and neck cancer undergoing radiotherapy (RT).MethodsThis longitudinal study included 122 patients. Data were collected at three time points: baseline (T1), the third week of RT (T2) and the completion of RT (T3). The Common Terminology Criteria for Adverse Events was used to assess the symptom of dysphagia and other toxicities; the MD Anderson Dysphagia Inventory (MDADI) was used to assess the patient-perceived swallowing functional outcomes; the nutritional status was evaluated by the weight ratio and the Patient-Generated Subjective Global Assessment (PG-SGA). The generalised estimating equation (GEE) was used to measure the correlation of MDADI with the weight ratio or PG-SGA and also to analyse the influential factors of swallowing functional outcomes.ResultsThe participants’ acute dysphagia rates were 5.7% at T1, 69.7% at T2 and 77.9% at T3. The swallowing functional outcomes worsen over RT (p<0.001) and were associated with weight ratio (β=0.032, p=0.008) and PG-SGA (β=−0.115, p<0.001). GEE models showed that patients with cancer of the pharynx region, advanced stage, chemoradiotherapy and high RT dose perceived worse swallowing functional outcomes. Oral mucositis, pharynx mucositis and salivary gland inflammation were positively correlated with swallowing functional outcomes, and the pharynx mucositis presented the highest absolute value of β.ConclusionThe swallowing functional outcomes were negatively correlated with nutritional status. Healthcare professionals should identify early on the population at higher risk and focus on multiple toxicities, especially the management of pharynx mucositis, to improve nutritional status.
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