Dieleman L A, Goerres M S, Arends A, Sprengers D, Torrice C, Hoentjen F, Grenther W B, Sartor R B
Center for Gastrointestinal Biology and Disease and Division of Digestive Diseases, University of North Carolina at Chapel Hill, North Carolina 27599-7038, USA.
Gut. 2003 Mar;52(3):370-6. doi: 10.1136/gut.52.3.370.
Bacteroides vulgatus induces colitis in gnotobiotic HLA-B27 transgenic (TG) rats while broad spectrum antibiotics prevent and treat colitis in specific pathogen free (SPF) TG rats although disease recurs after treatment ends. Lactobacilli treat human pouchitis and experimental colitis. We investigated if Lactobacillus rhamnosus GG (L GG) can prevent colitis in TG rats monoassociated with B vulgatus and if L GG or Lactobacillus plantarum 299v (LP 299v) can treat established colitis in SPF TG rats and prevent recurrent disease after antibiotics were stopped.
Germfree B27 TG rats were monoassociated with B vulgatus for four weeks following two weeks of colonisation with L GG or no bacteria. SPF B27 TG rats received oral vancomycin and imipenem for two weeks, or water alone, followed by four weeks of treatment with oral L GG, LP 299v, or water only. Disease activity was quantified by blinded gross and histological scores, caecal myeloperoxidase (MPO) activity, and levels of interleukin (IL)-1 beta, tumour necrosis factor (TNF), transforming growth factor beta, and IL-10.
L GG did not prevent colitis in B vulgatus co-associated TG rats or treat established disease in SPF rats. However, L GG but not LP 299v prevented colitis relapse in antibiotic treated rats with reduced gross and histological scores, caecal MPO, IL-1 beta, and TNF whereas caecal IL-10 was increased.
L GG does not prevent colitis in gnotobiotic TG rats or treat established disease in SPF rats, but is superior to LP 299v in the prevention of recurrent colitis. These studies suggest that antibiotics and probiotic agents provide synergistic therapeutic effects, perhaps mediated by altered immunomodulation with selective activity of different lactobacillus species.
普通拟杆菌可在无菌的HLA - B27转基因(TG)大鼠中诱发结肠炎,而广谱抗生素可预防和治疗无特定病原体(SPF)的TG大鼠的结肠炎,尽管治疗结束后疾病会复发。乳酸菌可治疗人类袋状结肠炎和实验性结肠炎。我们研究了鼠李糖乳杆菌GG(L GG)是否能预防与普通拟杆菌单联的TG大鼠的结肠炎,以及L GG或植物乳杆菌299v(LP 299v)是否能治疗SPF TG大鼠已形成的结肠炎,并在停用抗生素后预防疾病复发。
无菌的B27 TG大鼠在接种L GG或不接种细菌两周后,与普通拟杆菌单联四周。SPF B27 TG大鼠接受口服万古霉素和亚胺培南两周,或仅饮水,随后接受口服L GG、LP 299v或仅饮水四周的治疗。通过盲法大体和组织学评分、盲肠髓过氧化物酶(MPO)活性以及白细胞介素(IL)-1β、肿瘤坏死因子(TNF)、转化生长因子β和IL -10水平来量化疾病活动度。
L GG不能预防与普通拟杆菌共联的TG大鼠的结肠炎,也不能治疗SPF大鼠已形成的疾病。然而,L GG而非LP 299v可预防抗生素治疗大鼠的结肠炎复发,其大体和组织学评分、盲肠MPO、IL -1β和TNF降低,而盲肠IL -10增加。
L GG不能预防无菌TG大鼠的结肠炎,也不能治疗SPF大鼠已形成的疾病,但在预防复发性结肠炎方面优于LP 299v。这些研究表明,抗生素和益生菌具有协同治疗作用,可能是通过不同乳酸菌物种的选择性活性改变免疫调节介导的。