Figure 2.

Gut dysbiosis. Antibiotic treatment or other factors can disrupt the commensal microbial community, resulting in diminished resistance to colonization by pathogens and the outgrowth of indigenous pathobionts, such as Clostridium difficile. C. difficile can produce toxins, like TcdA and TcdB, that destroy the epithelial barrier and increase gut permeability. This toxin-mediated epithelial damage can cause systemic circulation of bacteria, which is associated with increasing systemic inflammation. Pathogen-induced gut inflammation confers a growth advantage to the pathogen through the generation of molecules such as inducible nitric oxide synthase (iNOS) by host innate immune cells leading to the release of nitrate (NO₃⁻), which can be used as an electron acceptor by Escherichia coli to generate energy through nitrate respiration. Pathogen infection results in the conversion of pro-IL-1β into the enzymatically active mature form of IL-1β, which promotes neutrophil recruitment and pathogen eradication. Bacterial toxins stimulate the NLRP3 inflammasome, driving the proteolytic activation of caspase-1, which results in the release of mature, biologically active IL-18 and IL-1β. Arrows represent increases (red) and decreases (blue) in bacterial abundances, metabolites and downstream effects observed in the antibiotic treated dysbiotic gut.