Ivnitsky Ju Ju, Schäfer T V, Rejniuk V L, Vakunenkova O A
Golikov Research Clinical Center of Toxicology, Federal Medical Biological Agency, St. Petersburg, Russia.
State Scientific Research Test Institute of Military Medicine, Ministry of Defense of the Russian Federation, St. Petersburg, Russia.
J Evol Biochem Physiol. 2022;58(4):1075-1098. doi: 10.1134/S0022093022040123. Epub 2022 Aug 28.
The last decade has been marked by an exponential increase in the number of publications on the physiological role of the normal human gut microbiota. The idea of a symbiotic relationship between the human organism and normal microbiota of its gastrointestinal tract has been firmly established as an integral part of the current biomedical paradigm. However, the type of this symbiosis varies from mutualism to parasitism and depends on the functional state of the host organism. Damage caused to the organism by external agents can lead to the emergence of conditionally pathogenic properties in the normal gut microbiota, mediated by humoral factors and affecting the outcome of exogenous exposure. Among the substances produced by symbiotic microbiota, there are an indefinite number of compounds with systemic toxicity. Some occur in the intestinal chyme in potentially lethal amounts in the case they enter the bloodstream quickly. The quick entry of potential toxicants is prevented by the intestinal barrier (IB), a set of structural elements separating the intestinal chyme from the blood. Hypothetically, severe damage to the IB caused by exogenous toxicants can trigger a leakage and subsequent systemic redistribution of toxic substances of bacterial origin. Until recently, the impact of such a redistribution on the outcome of acute exogenous poisoning remained outside the view of toxicology. The present review addresses causal relationships between the secondary dysfunction of the IB and complications of acute poisoning. We characterize acute systemic toxicity of such waste products of the normal gut microflora as ammonia and endotoxins, and demonstrate their involvement in the formation of such complications of acute poisoning as shock, sepsis, cerebral insufficiency and secondary lung injuries. The principles of assessing the functional state of the IB and the approaches to its protection in acute poisoning are briefly considered.
在过去十年中，关于正常人体肠道微生物群生理作用的出版物数量呈指数级增长。人体与其胃肠道正常微生物群之间的共生关系这一概念已被牢固确立，成为当前生物医学范式的一个组成部分。然而，这种共生的类型从互利共生到寄生不等，取决于宿主生物体的功能状态。外部因素对生物体造成的损害可导致正常肠道微生物群出现条件致病性，这是由体液因素介导的，并影响外源性暴露的结果。在共生微生物群产生的物质中，有数量不定的具有全身毒性的化合物。有些化合物在肠道食糜中以潜在致死量存在，一旦它们迅速进入血液。肠道屏障（IB）可防止潜在毒物的快速进入，肠道屏障是一组将肠道食糜与血液分隔开的结构元件。据推测，外源性毒物对肠道屏障造成的严重损害可引发细菌源性有毒物质的泄漏及随后的全身重新分布。直到最近，这种重新分布对急性外源性中毒结果的影响仍未被毒理学所关注。本综述探讨了肠道屏障继发性功能障碍与急性中毒并发症之间的因果关系。我们描述了正常肠道微生物群的此类废物（如氨和内毒素）的急性全身毒性，并证明它们参与了急性中毒并发症（如休克、败血症、脑功能不全和继发性肺损伤）的形成。简要考虑了评估肠道屏障功能状态的原则以及在急性中毒中保护肠道屏障的方法。
