中国医科大学附属盛京医院 李德天教授
新生儿出生之后，会直接接触来自母体以及周围环境中的微生物，同时这些微生物会快速地在婴儿体内定植。在整个生命周期中，人体与微生物之间不断发生各种相互作用，保持着一种互惠互利的关系。
肠道微生物被称作是人类的第二大脑，会影响我们的胃口、心情甚至胖瘦。80%的微生物都集中在肠道。肠道菌群分为三类，以双歧杆菌、乳酸杆菌等为代表的益生菌、以阴沟肠杆菌为代表的有害菌以及人畜无害的中性菌。无毒、无害、非致病性耗氧微生物暂时在肠道内定植，使局部环境氧分子浓度降低，营造适合正常肠道优势菌群——厌氧菌生长的微环境，促进厌氧菌的生长，最终恢复正常的微生态平衡。
人体体表/体腔菌群种类达500余种，数量达100万亿个，重量约1271 g，相当于肝脏重量的99.9%，是以双歧杆菌和类杆菌为主的专性厌氧菌。其中，0.1%是以肠杆菌科细菌为主的兼性厌氧菌。肠道正常菌群具有促进微生态平衡及保护宿主健康的作用，具体生理功能如下：（1）代谢与营养吸收。（2）胃肠免疫屏障。（3）生物化学屏障。（4）维持内环境稳定。（5）生物拮抗作用。（6）抑癌作用。
微生物之间相互制约、相互排斥。正常微生物群具有以下特点：（1）可形成生物屏障，防止外籍菌侵入。（2）降低肠道微环境pH，从而抑制外籍菌生长。（3）营养争夺占优势，限制外籍菌生长繁殖。（4）产生类抗生素物质，抑制、杀伤外籍菌。
慢性肾脏病（CKD）时
肠道微环境的变化与危害
正常情况下，人体产生的多种尿毒症毒素可通过肠道入血，经由肾脏排出。但CKD患者由于肾功能减退，肾脏功能受损导致体内尿毒症毒素积聚。而尿毒症毒素又可影响肠道微生物和肠壁完整性，影响毒素的产生和炎症状态，增加CKD的全身并发症和病死率。CKD时微生物组学发生变化，有益菌减少，有害菌增多（表1），导致肠源性尿毒症毒素增多，如硫酸吲哚酚、氧化三甲胺。
表1 CKD时肠道菌群的变化
CKD和肠道菌群相互影响，形成恶性循环。肠道菌群失调影响肾功能，CKD对肠道微生物谱也有很大的影响，肠道微生物谱又对尿毒症毒素的水平非常敏感。CKD患者体液中尿素浓度升高导致其扩散到肠腔，被尿素酶转化为氨，最后水解为氢氧化铵。氢氧化铵可作用于连接蛋白，破坏上皮屏障。受损的上皮屏障导致细菌、毒素进入循环，从而引发恶性循环，加剧CKD的进展。CKD时由于医源性原因和尿毒症，可引起菌群失调，可直接导致尿毒症毒素增加。
此外，由于肾脏排泄减少，肾功能的进行性损害增加了这些毒素在循环中的浓度。这种恶性循环使CKD恶化，并导致包括胰岛素抵抗、蛋白质营养不良、免疫失调和动脉粥样硬化等多种合并症。尿毒症毒素促进活性氧的形成与抗氧化能力之间的失衡，导致氧化应激过多。活性氧增加可诱导炎症、内皮功能障碍、动脉粥样硬化和纤维化，加速CKD进展。
CKD肠道微环境失衡的处理
1.改变饮食成分
可以改善CKD患者肠道菌群失调，降低尿毒症毒素水平，或恢复CKD患者肠黏膜通透性。地中海饮食、极低蛋白饮食可补充营养；高抗性淀粉饮食可补充短链脂肪酸。
2.补充益生菌
益生元、益生菌和共生菌可通过选择性增加结肠内的糖水解菌（消化膳食纤维）和减少蛋白水解菌（蛋白质和氨基酸发酵菌）来减少尿毒症毒素的生成。益生菌可调节肠道菌群，与致病菌竞争黏附位点，维持肠道微生态系统平衡；刺激肠黏膜产生抗炎细胞因子以提高肠道免疫性能；改善肠黏膜细胞紧密连接，提高紧密连接蛋白表达，增强肠道上皮屏障功能；发挥免疫调节作用，维持机体正常的免疫功能，改善肠道黏膜局部和系统免疫功能。益生元是一种不可消化的食物成分，通过选择性发酵，使胃肠道微生物群的组成或活性发生特定变化。在CKD大鼠模型中，富含抗性淀粉的饮食可延缓CKD的进展，并减轻氧化应激和炎症。
益生元、益生菌和共生菌为CKD相关肠道菌群失调的治疗提供了一种选择，可能在延缓CKD进展和预防相关并发症（如死亡和心血管风险）方面发挥作用。
3.洗涤菌群移植
洗涤菌群移植可改善肾功能不全患者的肾功能。该方法通过调节肠道菌群，促进毒性代谢产物的排泄，改善肾功能不全患者的肾功能，为治疗CKD提供了一种安全有效的新方法。
4.其他方法
改善CKD患者肠道菌群失调的其他方法如下：（1）使用吸附剂或磷酸盐结合剂AS-120/司维拉姆。（2）强化透析来提高尿毒症毒素清除率。（3）进行中药治疗，利用白蛋白结合置换器等方式抑制肠源性毒素的来源。
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#7d90a9;--weui-TEXTGREEN: #259c5c;--weui-FG: #fff;--weui-BG: #000;--weui-TAG-TEXT-RED: rgba(250, 81, 81, .6);--weui-TAG-BACKGROUND-RED: rgba(250, 81, 81, .1);--weui-TAG-TEXT-ORANGE: rgba(250, 157, 59, .6);--weui-TAG-BACKGROUND-ORANGE: rgba(250, 157, 59, .1);--weui-TAG-TEXT-GREEN: rgba(6, 174, 86, .6);--weui-TAG-BACKGROUND-GREEN: rgba(6, 174, 86, .1);--weui-TAG-TEXT-BLUE: rgba(16, 174, 255, .6);--weui-TAG-BACKGROUND-BLUE: rgba(16, 174, 255, .1);--weui-TAG-TEXT-BLACK: rgba(255, 255, 255, .5);--weui-TAG-BACKGROUND-BLACK: rgba(255, 255, 255, .05)}}@media screen and (min-width:1024px){body:not(.pages_skin_pc) .wx-root[data-weui-theme=dark],body:not(.pages_skin_pc) body[data-weui-theme=dark]{--appmsgExtra-BG: #121212}}@media screen and (min-width:1024px){body:not(.pages_skin_pc)body:not(.pages_skin_pc){background:var(--weui-BG-2)}}@media screen and (min-width:1024px) and (prefers-color-scheme:dark){body:not(.pages_skin_pc) 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rgba(250, 157, 59, .6);--weui-TAG-BACKGROUND-ORANGE: rgba(250, 157, 59, .1);--weui-TAG-TEXT-GREEN: rgba(6, 174, 86, .6);--weui-TAG-BACKGROUND-GREEN: rgba(6, 174, 86, .1);--weui-TAG-TEXT-BLUE: rgba(16, 174, 255, .6);--weui-TAG-BACKGROUND-BLUE: rgba(16, 174, 255, .1);--weui-TAG-TEXT-BLACK: rgba(255, 255, 255, .5);--weui-TAG-BACKGROUND-BLACK: rgba(255, 255, 255, .05)}}@media screen and (min-width:1024px) and (prefers-color-scheme:dark){body:not(.pages_skin_pc) .wx-root:not([data-weui-theme=light]),body:not(.pages_skin_pc) body:not([data-weui-theme=light]){--weui-BG-0: #111;--weui-BG-1: #1e1e1e;--weui-BG-2: #191919;--weui-BG-3: #202020;--weui-BG-4: #404040;--weui-BG-5: #2c2c2c;--weui-FG-0: rgba(255, 255, 255, .8);--weui-FG-HALF: rgba(255, 255, 255, .6);--weui-FG-1: rgba(255, 255, 255, .5);--weui-FG-2: rgba(255, 255, 255, .3);--weui-FG-3: rgba(255, 255, 255, .1);--weui-FG-4: rgba(255, 255, 255, .15);--weui-FG-5: rgba(255, 255, 255, .1);--weui-RED: #fa5151;--weui-ORANGERED: 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