Abstract
Recent studies have demonstrated that antibiotics/or probiotics administration in early life play key roles on modulating intestinal microbiota and the alterations might cause long-lasting consequences both physiologically and immunologically. We investigated the effects of early life ceftriaxone, vancomycin and Bifidobacterium bifidum TMC3115 (TMC3115) treatment on intestinal microbiota and immunity both in neonates and adults even after termination of antibiotics exposure. We found that ceftriaxone and vancomycin, but not TMC3115, significantly altered the intestinal microbiota, serum total IgE level, and the morphology and function of the intestinal epithelium in the neonatal mice. In the adult stages, the diversity and composition of the intestinal microbiota were significantly different in the antibiotic-treated mice, and ceftriaxone-treated mice exhibited significantly higher serum total IgE and OVA-specific IgE levels. TMC3115 significantly mitigated the alteration of intestinal microbiota caused by ceftriaxone not vancomycin. Antibiotics and TMC3115 can differently modulate intestinal microbiota and SCFAs metabolism, affecting the development and function of the immunity and intestinal epithelium to different degrees in neonatal mice. Neonatal ceftriaxone-induced abnormal intestinal microbiota, immunity and epithelium could last to adulthood partly, which might be associated with the enhancement of host susceptibility to IgE-mediated allergies and related immune responses, TMC3115 may protect against the side effects of antibiotic treatment, at least partly.
Highlights
Allergic diseases are becoming a serious global public health problem, especially in industrialized countries, and are sharply increasing, even in developing countries such as China[1,2]
There was no significant difference in the growth rate of mice among groups (Fig. 1b)
The spleen index of mice at postnatal day (PND) 21 was calculated (Fig. 1d), and that of the mice exposed to ceftriaxone and vancomycin was significantly decreased compared with the control (P < 0.001)
Summary
Allergic diseases are becoming a serious global public health problem, especially in industrialized countries, and are sharply increasing, even in developing countries such as China[1,2]. Germ-free and antibiotic-treated mice showed higher serum IgE levels than conventional mice[11,12], and the serum IgE levels started increasing in germ free mice early in life, around 3–4 weeks of age, correlating with the time of weaning[13] These results suggest that the intestinal microbiota built in early life might be significantly involved in the development of allergic disorders[14]. Several studies have indicated that some selective probiotic strains greatly promote the growth of neonatal mice through enhancing the morphological development of IECs and functional differentiation, at least partly[29,30] It remains unclear whether probiotics, especially bifidobacteria, which usually colonize in the intestine of host animals from early life, can alleviate the side effects of antibiotics on the host animal in the neonate and adult stages. We wanted to determine if TMC3115 could protect adult hosts from allergic disorders caused by antibiotic-altered intestinal microbiota and immune function in their early life
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