Abstract
Antibiotic exposure in early life can lead to a significant change of the gut microbiota and may contribute to later onset of inflammatory bowel disease (IBD). However, the relationship between early-life antibiotic treatment and IBD is ambiguous, according to contradicting results of epidemiologic studies. In the present study, we demonstrated that low-dose penicillin pre-treatment had a unique protective effect against mouse colitis induced by dextran sodium sulfate (DSS). Low-dose penicillin also suppressed the expression of pro-inflammatory cytokine IL-17 in various intestinal tissues, and decreased the amount of Th17 cells in small-intestine lamina propria. Neither metronidazole nor enrofloxacin had a similar effect. We further confirmed that low-dose penicillin could cause specific changes of the gut microbiota, especially the eradication of segmented filamentous bacteria (SFB). Mice without SFB inoculation showed no disparity when treated with penicillin or water. Taken together, the results showed that low-dose penicillin can achieve a highly specific manipulation of sensitive bacteria and interfere with development of intestinal immune system in early life. The study may further indicate the possibility of achieving a favorable immune state among a certain group of patients with IBD, or other autoimmune diseases, by fine-tuning the gut microbiota.
Highlights
Antibiotic exposure in early life can lead to a significant change of the gut microbiota and may contribute to later onset of inflammatory bowel disease (IBD)
We further examined the perturbation of gut microbiota and immune system by penicillin, and demonstrated the protection was dependent on the eradication of segmented filamentous bacteria (SFB) in the intestine
We examined the impact of low-dose antibiotic pre-treatment on intestinal inflammation with a mouse model
Summary
Antibiotic exposure in early life can lead to a significant change of the gut microbiota and may contribute to later onset of inflammatory bowel disease (IBD). We further confirmed that low-dose penicillin could cause specific changes of the gut microbiota, especially the eradication of segmented filamentous bacteria (SFB). The results showed that low-dose penicillin can achieve a highly specific manipulation of sensitive bacteria and interfere with development of intestinal immune system in early life. A meta-analysis including several epidemiological reports from western countries showed a significant association between early-life antibiotic consumption and newly-onset Crohn’s disease, especially among children[3]. A recent study in Asia indicated an inverse association of antibiotic use and development of IBD4 Another survey found antibiotic consumption increased the risk of CD and UC among Caucasians but decreased the risk among Middle Eastern migrants[5]. We further examined the perturbation of gut microbiota and immune system by penicillin, and demonstrated the protection was dependent on the eradication of segmented filamentous bacteria (SFB) in the intestine
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