长链菊粉对抗生素处理后小鼠肠道菌群重建的影响

Effects of long-chain inulin on the reconstruction of gut microbiota in mice after antibiotics treatment

摘要:

[目的] 评价长链菊粉对抗生素致小鼠肠道菌群失调后肠道菌群的恢复情况。[方法] 选择50只健康的10周龄BALB/c小鼠，随机分为2组，其中15只为正常对照组，余下35只饮用水中含4种抗生素连续喂养7 d，诱导小鼠肠道菌群严重失调后，再随机分为长链菊粉恢复组（饮用水中添加5%（W/W）长链菊粉）和自发恢复组（饮用水为无菌水），连续处理21 d。受试小鼠在抗生素治疗后的第7天以及恢复喂养的第7、14和21天，取结肠组织进行切片然后进行HE染色分析，无菌取粪便进行16S rRNA测序分析，观察小鼠肠道组织及菌群恢复情况。[结果] 抗生素处理7 d后，小鼠结肠组织有轻微炎症，但肠道菌群严重失调。组织学分析表明，在补充长链菊粉或自发恢复21 d后，结肠炎症逐渐减轻；但相比于自发恢复，长链菊粉干预延迟了结肠组织的恢复。16S rRNA基因V3-V4区扩增子测序分析显示无论是长链菊粉补充还是自发恢复都无法在属水平上恢复肠道菌群组成。尤其是长链菊粉的补充，反而导致了某些机会致病菌的选择性扩增，并提高了与肠道菌群相关的疾病途径。[结论] 抗生素诱导肠道菌群严重失调后补充长链菊粉会延迟肠道菌群的重建，可能会导致潜在的不良影响。

Abstract:

[Objective] To investigate the effects of long-chain inulin supplementation on the gut microbiota recovery after antibiotics treatment induced dysbiosis. [Methods] Fifty healthy 10-week-old BALB/c mice were randomly divided into 2 groups, 15 mice were used as controls (the Ctrl group), and the remaining 35 mice were provided water containing 4 antibiotics (the ABx group) ad libitum for 7 days. On the 8th day, the antibiotic-induced dysbiosis mice were randomly divided into 2 groups. One group was provided drinking water containing 5% inulin as the inulin recovery group (the Ire group), and the other group received normal drinking water as the spontaneous recovery group (the Sre group). The treatment continued for 21 continuous days. On the 7th day after ABx treatment and on the 7th, 14th and 21th day of the recovery treatment, the colon samples were collected and subjected to histological analysis; the feacal samples were collected and subjected to 16S rRNA V3-V4 region sequencing and analyzed with bioinformatic softwares. [Results] The antibiotics treatment induced slight colonic inflammation but serious gut microbiota dysbiosis. Histological analysis showed that the colonic inflammation gradually decreased after 21 days of either long chain inulin supplementation or spontaneous recovery. However long-chain inulin intervention delayed the recovery of colon tissue compared to spontaneous recovery. Neither inulin supplementation nor spontaneous recovery could restore gut microbiota composition at the genus level. In particular, long-chain inulin supplementation might result in selective expansion of some opportunistic pathogens and elevated the pathways associated with diseases linked to gut microbiota function. [Conclusion] Long-chain inulin supplementation, after antibiotic-induced severe gut microbiota dysbiosis, delayed the reconstruction of the gut microbiota and might led to potential adverse effects.