Critically ill patients and intestinal microbiota
An article entitled The intestinal microbiota and host immune interactions in the critically ill, by TJ Schuitj and co-workers, and published recently in Trends in Microbiology, nicely reviews the complex set of issues caregivers need to be aware of with this set of patients (note: this article may be downloaded without cost while logged into the York College network.) All BIO230 students should find the article relatively easy to follow, particularly as we work through Chapter 15 on Innate Immunity. The article begins by summarizing the diversity of microorganisms in the healthy human gut. Surprisingly, across all human cultures, the composition of the intestinal microbiota can be organized into three broad clusters or enterotypes, and these clusters are independent of continental or national location. Recent research suggests that people with the different enterotypes might potentially respond differently to different drugs and diets, and so further study of the specific composition between healthy individuals and the role that these enterotypes play in normal health is important.
It is easy to think of the microorganisms of the mammalian gut as being free loaders with little contribution to the host, however the presence of the normal microbiota is actually very important for proper health. The principle of competitive exclusion or microbial antagonism has been brought up previously in class; the presence of relatively benign microorganisms can prevent the overgrowth of more pathogenic microorganism. This principle has been further used to postulate that microorganisms now missing from frequent human contact (parasitic worms for instance) have led to increased levels of autoimmune and allergic diseases in modern human societies, in a hypothesis called the “hygiene hypothesis.” However, the benefit of these normal organisms goes significantly further than that, as illustrated by Figure 1c from this article. The presence of the normal microbial flora is also critical to break down dietary components into a form that the human intestine can adsorb, and these organisms also produce a number of compounds such as vitamins that our bodies are unable to make on their own. In the absence of these microorganisms, the majority of foodstuff passes through the small intestine essentially undigested and moves out of the body.
In the critically ill patient, this complex set of interactions is disrupted. The mucosal barrier can become damaged due to disease, trauma, or medicine, which in turn can allow microorganisms to more easily penetrate into tissue leading to sepsis. Furthermore, the homeostatic balance between the normal microbiota and the host also becomes altered. Fecal analysis of essential bacterial metabolites such as short chain fatty acids is statistically decreased in the critically ill patient, in comparison to healthy individuals. This results argues that the absolute numbers of these beneficial bacteria are diminished.
Several medical treatments in the critically ill further affect this balance. Antibiotic use is the most obvious; the short-term balance of the normal microbiota can be severely disrupted, particularly by the use of broad spectrum antibiotics. Anti-hypotensive drugs used to raise blood pressure in instances of shock can lead to a lowered pH in the intestine and modify bacterial populations. Long-term parental feeding presents diminished nutrients in the intestines, and can immediately lead to lower numbers and diminished diversity of normal bacteria. Long term use of opiates for severe pain relief has been correlated with bacterial overgrowth. The combination of all of these treatments is associated with poor patient outcomes. It is not clear at this point whether the alterations observed in the microbiota of all critically ill patients are a cause or an effect of their illness.
The review article ends with the interesting premise of suggesting that modulating the intestinal microbiota in these patients might lead to novel supportive therapies. Obviously, critically ill patients come to their situation for many different reasons, only some of which are the result of infectious disease. If the premise that the altered microbiota is a consequence of the disease is valid, one can imagine that promoting beneficial microbiota, either by direct supplementation with cultured organisms (probiotic), or by dietary supplements that promote their growth (prebiotic) means.