Lima W G, Pessoa R M, Vital K D, Takenaka I K T M, Cardoso V N, Fernandes S O A
Laboratório de Radioisótopos, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos 6627 Pampulha, 31270-901 Belo Horizonte, MG, Brazil.
Laboratório de Genômica Médica, Centro Internacional de Pesquisa e Ensino (CIPE) - A.C. Camargo Cancer Center, Rua Taguá, 01508010 São Paulo, SP, Brazil.
Benef Microbes. 2020 Aug 12;11(4):305-318. doi: 10.3920/BM2019.0142. Epub 2020 Jun 3.
Gastrointestinal mucositis (GIM) is an inflammation caused by antitumor therapy, especially after chemotherapy and radiotherapy. Currently in the clinical practice, only palliative measures are taken to treat GIM, representing the main clinical limitation in the management of this condition. Several studies have highlighted the potential benefits of probiotics for the management of GIM, but the actual role of these microorganisms in the maintenance of intestinal homeostasis remains elusive. In this context, here we aimed to realise a systematic review with meta-analysis to evaluate the effect of probiotics on experimental GIM. The meta-analysis showed that probiotics significantly suppressed the body weight loss related to GIM in rodents (95% confidence interval (CI): -2.67 to -0.70; I=98%, <0.00). Subgroup analysis showed that pre-treatment (≥7 days before chemotherapy) (95% CI: -8.84 to -0.17; I=98%, <0.04) with a high dose of probiotics (≥ 10 cfu/day) (95% CI: -2.58 to -0.28; I=98%, <0.00) comprising two or more microorganism species (95% CI: -6.49 to -0.28; I=96%, =0.03) remedied GIM more effectively. It was also revealed that fungi (specifically ) are more effective in remedying GIM than bacteria (=0.03 vs <0.00), and the mouse models are more receptive than rats to the enteroprotective effects of probiotics (95% CI: -4.76, -0.69; I=97%, =0.01). Qualitative analyses highlighted that probiotics suppress GIM through several mechanisms; they reduce the intestinal permeability, suppress the pro-inflammatory cytokine production while stimulating production and secretion of anti-inflammatory cytokines, inhibit the signalling pathways coupled to inflammation and apoptosis, accelerate the proliferation of enterocytes, reduce the levels of reactive oxygen species, and help maintain the protective mucus layer. In conclusion, this review highlights the therapeutic benefits of probiotics in experimental GIM.
胃肠道黏膜炎（GIM）是一种由抗肿瘤治疗引起的炎症，尤其是在化疗和放疗之后。目前在临床实践中，治疗GIM仅采取姑息措施，这是该病症管理中的主要临床局限。多项研究强调了益生菌在GIM管理中的潜在益处，但这些微生物在维持肠道内稳态方面的实际作用仍不明确。在此背景下，我们旨在进行一项系统评价并荟萃分析，以评估益生菌对实验性GIM的影响。荟萃分析表明，益生菌显著抑制了啮齿动物中与GIM相关的体重减轻（95%置信区间（CI）：-2.67至-0.70；I² = 98%，P < 0.00）。亚组分析显示，高剂量（≥10¹¹ cfu/天）（95% CI：-2.58至-0.28；I² = 98%，P < 0.00）的益生菌进行预处理（化疗前≥7天）（95% CI：-8.84至-0.17；I² = 98%，P < 0.04），且包含两种或更多微生物种类（95% CI：-6.49至-0.28；I² = 96%，P = 0.03）能更有效地缓解GIM。研究还表明，真菌（特别是 ）在缓解GIM方面比细菌更有效（P = 0.03 vs P < 0.00），并且小鼠模型比大鼠对益生菌的肠保护作用更敏感（95% CI：-4.76，-0.69；I² = 97%，P = 0.01）。定性分析强调，益生菌通过多种机制抑制GIM；它们降低肠道通透性，抑制促炎细胞因子的产生，同时刺激抗炎细胞因子的产生和分泌，抑制与炎症和细胞凋亡相关的信号通路，加速肠上皮细胞的增殖，降低活性氧水平，并有助于维持保护性黏液层。总之，本综述强调了益生菌在实验性GIM中的治疗益处。
