Exogenous antibiotic resistance gene contributes to intestinal inflammation by modulating the gut microbiome and inflammatory cytokine responses in mouse

Abstract

Dysregulation of the gut microbiota by environmental factors is associated with a variety of autoimmune and immune-mediated diseases. In addition, naturally-occurring extracellular antibiotic resistance genes (eARGs) might directly enter the gut via the food chain. However, following gut microbiota exposure to eARGs, the ecological processes shaping the microbiota community assembly, as well as the interplay between the microbiota composition, metabolic function, and the immune responses, are not well understood. Increasing focus on the One Health approach has led to an urgent need to investigate the direct health damage caused by eARGs. Herein, we reveal the significant influence of eARGs on microbiota communities, strongly driven by stochastic processes. How eARGs-stimulate variations in the composition and metabolomic function of the gut microbiota led to cytokine responses in mice of different age and sex were investigated. The results revealed that cytokines were significantly associated with immunomodulatory microbes, metabolites, and ARGs biomarkers. Cytokine production was associated with specific metabolic pathways (arachidonic acid and tryptophan metabolic pathways), as confirmed by ex vivo cytokine responses and recovery experiments in vivo . Furthermore, the gut microbial profile could be applied to accurately predict the degree of intestinal inflammation ascribed to the eARGs (area under the curve = 0.9616). The present study provided a comprehensive understanding of the influence of an eARGs on immune responses and intestinal barrier damage, shedding light on the interplay between eARGs, microbial, metabolites, and the gut antibiotic resistome in modulating the human immune system.

Anthocyanins from purple corn affect gut microbiota and metabolome in IBD patients under Infliximab infusion: the SiCURA pilot study

“…Oppositely other evidence, in line with our results, found a positive correlation between Alistipes and arachidonic acid [43]. However, the same study focused on extracellular antibiotic resistance genes, defined…”

Uterine Tissue Metabonomics Combined with 16S rRNA Gene Sequencing To Analyze the Changes of Gut Microbiota in Mice with Endometritis and the Intervention Effect of Tau Interferon

“…Metabolic stress leads to inflammation, and inflammation itself will destroy the metabolic balance of the body. Therefore, metabolic disorder and inflammatory reaction may form a vicious circle ( 32 ). Therefore, these results indicated that IFN-τ participated in these metabolic pathways to interfere with the inflammatory response.…”

Effects of antibiotic resistance genes on health risks of rivers in habitat of wild animals under human disturbance – based on analysis of antibiotic resistance genes and virulence factors in microbes of river sediments

“…For the ARGs in rivers could enter the body by drinking water (Zhang, Qin, et al, 2021), it is indicated that the ARGs in the rivers with nature reserves of wild animals could be moved to wild animals by drinking. The gut microbiota plays a vital role in the health of wild animals by providing essential nutritional services and protection against the invasion of intestinal pathogens (Fackelmann et al, 2021), and regulating multiple aspects of microbial metabolite pools that could affect the gut barrier and the polarization of immune cells (Tan et al, 2023). Many studies have shown that ARGs can be transferred into the gut microbiota (Khan et al, 2020;Lamberte & van Schaik, 2022;Rolain, 2013), if the ARGs entry into the gut will have a significant impact on the gut microbiota, which may lead to various diseases and represent unknown risks to wild animals (Zhu et al, 2021).…”