Exposure to antibiotics affects saponin immersion induced immune stimulation and shift in microbial composition in zebrafish larvae

Abstract

In the last decades, pollution of the environment by large scale use of antibiotics in agriculture and human medicine have led to increased antimicrobial resistance in both the environment and the host animal microbiome. Disturbances in the host microbiome can result in impaired immunity and reduced resilience of aquaculture species. Here, we investigated whether environmentally measured levels of the commonly used antibiotics ciprofloxacin and oxytetracycline influences the host microbiome and susceptibility toward saponin-induced immune stimulation in larval zebrafish. Firstly, neutrophil and macrophage reporter zebrafish larvae were exposed to different concentrations of soy saponin by immersion. A dose-dependent increase in neutrophil presence in the intestinal area was observed together with increased expression of immune genes il1b, tnfa, il22 and mmp9. To investigate the effect of antibiotics, larval zebrafish were immersed in ciprofloxacin or oxytetracycline in the presence or absence of a low dose of saponin. In vivo imaging revealed that antibiotic treatment did not reduce the number of neutrophils that were recruited to the intestinal area upon saponin exposure, although it did tend to lower pro-inflammatory cytokine levels. Microbial sequencing of whole larvae revealed that exposure to a low dose of saponin already shifted the microbial composition. The combination of oxytetracycline and saponin significantly increased αdiversity compared to the controls. In conclusion, the current study provides evidence that the combination of low levels of antibiotics with low levels of anti-nutritional factors (saponin) can induce inflammatory phenotypes and can modify the microbiota, which might lead to altered disease susceptibility.

Antibiotic-induced alterations and repopulation dynamics of yellowtail kingfish microbiota

“…For example, a loss of gut diversity was observed in Atlantic salmon following oxytetracycline treatment [62], in channel catfish (Ictalurus punctatus) following florfenicol treatment [63], in fathead minnow (Pimephales promelas) after triclosan use [64] and in zebrafish following olaquindox treatment [65]. In contrast, in some cases, it has been reported that antibiotic treatment may even increase or cause a shift in species diversity, as shown for Atlantic salmon and zebrafish [12,13], and pacu (Piaractus mesopotamicus) [8] respectively. This is pertinent given that changes in diversity and evenness within the gut has been suggested to influence functional capacity and disease resilience [66].…”

“…Many of the antibiotics used in the aquaculture industry are considered to be broad-spectrum, and may indiscriminately act on both the pathogenic and commensal constituents [11]. Perturbation of the gut microbiota following antibiotic exposure has been reported in various fish species [8,12,13] and may be associated with changes in microbial enzymatic activity, gene expression, and protein and metabolite synthesis [14]. In humans and other animals, antibiotic use may have prolonged effects on the gut bacterial composition, leading to widespread perturbations and the extinction of some species [15].…”

Antibiotic-induced alterations and repopulation dynamics of yellowtail kingfish microbiota

“…For example, a loss of gut diversity was observed in Atlantic salmon following oxytetracycline treatment [62], in channel cat sh (Ictalurus punctatus) following orfenicol treatment [63], in fathead minnow (Pimephales promelas) after triclosan use [64] and in zebra sh following olaquindox treatment [65]. In contrast, in some cases, it has been reported that antibiotic treatment may even increase or cause a shift in species diversity, as shown for Atlantic salmon and zebra sh [12,13], and pacu (Piaractus mesopotamicus) [8] respectively. This is pertinent given that changes in diversity and evenness within the gut has been suggested to in uence functional capacity and disease resilience [66].…”

“…Many of the antibiotics used in the aquaculture industry are considered to be broad-spectrum, and may indiscriminately act on both the pathogenic and commensal constituents [11]. Perturbation of the gut microbiota following antibiotic exposure has been reported in various sh species [8,12,13] and may be associated with changes in microbial enzymatic activity, gene expression, and protein and metabolite synthesis [14]. In humans and other animals, antibiotic use may have prolonged effects on the gut bacterial composition, leading to widespread perturbations and the extinction of some species [15].…”

Antibiotic-induced alterations and repopulation dynamics of yellowtail kingfish microbiota

“…Many of the antibiotics used in the aquaculture industry are considered to be broad-spectrum, and may indiscriminately act on both the pathogenic and commensal constituents. Perturbation (dysbiosis) of the gut microbiota following antibiotic exposure has been reported in various fish species [8,11,12] and may be associated with changes in microbial enzymatic activity, gene expression, and protein and metabolite synthesis [13]. In humans and other animals, antibiotic use may have prolonged effects on the gut bacterial composition, leading to widespread dysbiosis and the extinction of some species [14].…”