Gut Microbiota Contributes to Host Defense Against Klebsiella pneumoniae-Induced Liver Abscess

Abstract

Purpose: Klebsiella pneumoniae-induced liver abscess (KLA) is a type of pyogenic liver abscess (PLA), which is a distinct invasive syndrome that has been increasingly reported worldwide over the past two decades. The intestinal microbiota is increasingly recognized as an important modulator that can promote and maintain host immune homeostasis. However, its precise role in liver abscess is unknown. We aimed to investigate the function of the gut microbiota in the host defense against K. pneumoniae infection. Methods: We constructed C57BL/6J mice with KLA and analyzed the diversity and richness of the intestinal microflora by 16S rRNA sequencing. Next, to create a microbiota-depleted (MD) mouse model, we administered multiple broad-spectrum antibiotics and validated the model using 16S rRNA sequencing. At 48 h after K. pneumoniae infection, we assessed the general health condition, liver injury, bacterial loads, and inflammatory factor levels in MD+KLA mice. Additionally, fecal microbiota transplantation (FMT) was conducted in another group of MD+KLA mice prior to K. pneumoniae infection, and we assessed whether the transplantation changed the outcomes. Results: The diversity of the intestinal flora was significantly changed in KLA mice compared to control mice, with a decrease in beneficial bacteria and an increase in harmful bacteria. The MD+KLA mice exhibited impaired antimicrobial capacity, reduced survival, increased inflammation and liver damage at 48 h after K. pneumoniae infection compared to the KLA mice. However, FMT normalized the inflammatory cytokine levels, reduced liver damage, and increased survival. Conclusion:This study identified the gut microbiota as a protective factor against K. pneumoniae infection. The role of FMT in KLA should be investigated in future clinical studies.

Fabrication of levofloxacin-loaded porcine acellular dermal matrix hydrogel and functional assessment in urinary tract infection

“…Previous studies have consistently indicated that the administration of levofloxacin can disturb the equilibrium of the intestinal microbiota, thereby inducing antibiotic-associated inflammation within the gastrointestinal tract [ 55 ]. Moreover, previous research conducted by our team and other scholars has provided evidence that the depletion of the intestinal microbiota resulting from the administration of antimicrobial drugs substantially elevates the likelihood of bacterial infectious diseases [ 53 , 54 , 72 – 74 ]. This correlation is closely linked to the reduction of immunoregulatory metabolites derived from the intestinal microbiota.…”

“…The perturbation of the gut microbiota resulting from the administration of antimicrobial agents is linked to dysregulation of the host immune system, thereby heightening vulnerability to diverse bacterial infections [53,54]. Prior investigations have unequivocally established that the modification of the gut microbiota composition brought about by levofloxacin intensifies the inflammatory reactions of the host [55].…”

Hypervirulent Klebsiella pneumoniae Strains Modulate Human Dendritic Cell Functions and Affect TH1/TH17 Response

“…Hv-Kp usually colonize the gastrointestinal (GI) tract [15], and, under certain circumstances (as for example, antibiotic-induced dysbiosis), they may spread to other organs and apparatus [16,32,33].…”

Gut Microbiota Was Involved in the Process of Liver Injury During Intra-Abdominal Hypertension

“…The relationship between the gut and liver is established by the gut-liver axis through the vascular path of the portal vein system that transfers gutderived metabolites directly to the liver and carries bile and antibody excreted from the liver to the intestine (Albillos et al, 2020). A variety of acute and chronic liver diseases, including pyogenic liver abscess (Zheng et al, 2021), nonalcoholic fatty liver disease (Boursier et al, 2016), alcoholassociated liver disease (Gu et al, 2021), and drug-induced liver injury (Gong et al, 2018(Gong et al, , 2021 are closely linked to disordered gut microbiota. We speculated that the gut flora may be one important switch of the host response to IAHrelated liver injury due to the reason that IAH leads to gut microbiota dysbiosis, which plays a critical role in the polymicrobial sepsis-induced liver injury (Gong et al, 2019).…”