Pay attention to the intestinal microecology of patients with sepsis

Pay attention to the intestinal microecology of patients with sepsis.   The intestinal microecology is very important in the normal host. It can regulate the immune function and play the role of intestinal barrier. Intestinal microecological structure and dysfunction are related to many diseases, such as Clostridium difficile infection, asthma, dysentery and so on. Intestinal microbiota is also related to sepsis.

First, before the outbreak of sepsis, changes in the intestinal microecology will increase the susceptibility to sepsis, making the host more prone to sepsis. The main mechanisms of this pathology are: 1. Intestinal flora growth; 2. Enhance pro-inflammatory response; 3. Reduce some substances beneficial to intestinal function (short-chain fatty acids, etc.).

Secondly, after the onset of sepsis, intestinal microecological disorders will increase the risk of MODS.

Third, can some preventive measures such as probiotics and selective digestive tract decontamination improve the prognosis of patients with sepsis? Are these measures safe? This requires further experiments to demonstrate. Case reports indicate that stool transplantation can induce intestinal microecological reconstruction and reduce inflammation, but its efficacy still needs to be further clarified.

Background

Sepsis refers to the abnormal immune response induced by infection with organ dysfunction. It is a major disease endangering public health, and its mortality rate is about 50%. The cornerstone of sepsis treatment is antibiotics and organ support, but over time, the fatality rate of sepsis has not improved significantly.

The intestinal microecology will change after the onset of sepsis and become a new measure and direction for sepsis treatment. Changes in intestinal microecological structure and function are related to many diseases, such as: Clostridium difficile infection, inflammatory gastrointestinal diseases, and obesity. The occurrence and development of sepsis is affected by many factors in the body, and the mechanism is not completely clear. However, more and more evidence proves that intestinal microecological disorders can aggravate the condition of sepsis and affect the prognosis.

Intestinal microecological disorders increase the risk of sepsis

The intestinal microecology is composed of many bacterial flora, called the diversity of the intestinal flora, which can be divided into α-diversity and β-diversity. The destruction of the diversity of the intestinal flora will cause some diseases of the body.

For a period of time after a newborn is born, some flora, including anaerobic flora, will appear in the intestines. These flora will protect the body from the influence of other flora. A prospective cohort study in 2019 found that newborns’ gut microbiota protects them from sepsis. If the body’s intestinal anaerobic bacteria are absent, then the patient will be more prone to staphylococcal and Escherichia coli infections.

For adults, what role did the gut microbiota play before sepsis? There are not many relevant studies at present. A study has shown that postoperative sepsis is related to changes in the intestinal microbiota. Studies have also pointed out that if the diversity of the intestinal flora is destroyed (more Gram-negative bacteria and enterococci appear), patients are more likely to develop sepsis.

Clostridium difficile infection and the use of broad-spectrum antibiotics can destroy the intestinal microbiome. A 2015 study showed that patients with Clostridium difficile infection are more likely to develop sepsis. Another study showed that if patients receive broad-spectrum antibiotics such as third-generation cephalosporin, fourth-generation cephalosporin, carbapenem, fluoroquinolone, etc., they are more likely to develop sepsis. This reflects from the side that the intestinal microecological disorder will increase the risk of sepsis.

An animal experiment showed that rats with different intestinal microbiota, after the appearance of sepsis, undergo the same treatment, their fatality rates are different, which indicates that the type of intestinal microbiota affects the fatality rate of sepsis. It shows that different intestinal microecology has different protective effects on the body.

Intestinal microecology and pathogenic bacteria

In the normal intestinal micro-ecological environment, it is difficult for pathogenic bacteria that parasitize in the body to proliferate, so the probability of disease is not high. After the intestinal microecological disorder, these pathogenic bacteria will proliferate and cause related diseases. Animal experiments have shown that the mice are induced to develop an inflammatory response and then treated with antibiotics (antibiotics will affect the diversity of the intestinal flora), and finally found that the multi-drug resistant Escherichia coli in the intestines of these mice proliferates significantly, and these multi-drug resistant The Escherichia coli will migrate throughout the body (extratopic flora appears).

In another animal experiment, a batch of tested mice received a high-fat diet and a batch of normal diets, but they all received broad-spectrum antibiotics, and then underwent partial hepatectomy. In the end, it was found that the α-polymorphism in the intestinal flora of mice on a high-fat diet was reduced, and they were more prone to gram-negative bacterial sepsis, and their survival rate was also lower; this indicates that intestinal polymorphism is very important to the body. Abnormal flora polymorphism can cause ectopic flora and reduce survival rate.

Intestinal microecology and immune response

The gut microbiota affects the immune response from birth. Reconstruction of the intestinal flora will reduce the possibility of immune disorders, thereby protecting the body from sepsis. The host of intestinal α-polymorphism has an increased probability of survival in sepsis because of increased CD4+ T cell reactivity.

In addition to cellular immunity, intestinal microecology can also affect humoral immunity. The intestinal microecology can induce the production of IgA, which plays a protective role.

When sepsis occurs, the gut microbiota will change. The main change is that the diversity of the gut microbiota decreases, and the immune function changes accordingly. At the same time, studies have shown that different intestinal flora hosts also produce different levels of cytokines in sepsis, and thus have different outcomes in sepsis.

Products of intestinal microbiota

The intestinal microecology can produce short-chain fatty acids, which can adjust the intestinal environment. Intestinal bacillus and faecalis can produce short-chain fatty acid butyrate, thereby regulating T cell differentiation, preventing histone deacetylation, and reducing the production of pro-inflammatory factors (TNF-α and IL-6).

Short-chain fatty acids are also very important in maintaining intestinal epithelial function. The acetate produced by bifidobacteria can protect the intestinal mucosa and prevent the ectopic E. coli. The metabolism of these short peptide fatty acids in the intestine requires the consumption of oxygen, and the reduction of oxygen will also affect the expression of some genes, such as HIF-1 factor. The reduction of intestinal butyrate-producing bacteria will make the body more prone to sepsis, increase the permeability of the intestinal barrier, and make it easier for the flora to be ectopic.

Sepsis exacerbates intestinal microecological disorders

Intestinal microecological disorders will make the body more prone to sepsis, such as the proliferation of pathogenic bacteria, immune dysfunction, and decreased production of short peptide fatty acids. After the onset of sepsis, the intestinal microecological disorder can further worsen, making the prognosis of sepsis worse.

How sepsis causes the intestinal microecological disorder is still unknown. The use of antibiotics is one of the reasons. Other factors include opioid sedatives, parenteral nutrition, proton pump inhibitors, etc.

At present, many studies have shown that the decrease of intestinal microecological diversity is related to the relative proliferation of pathogenic bacteria. The earliest study showed that patients with systemic inflammatory response syndrome decreased intestinal anaerobic bacteria, and pathogenic bacteria such as Staphylococcus and Pseudomonas aeruginosa increased. Obviously, these patients will receive antibiotic treatment. Through the latest genetic technology, it was discovered that the genus Faecalis in the intestinal microecology in sepsis will disappear, replacing the faecalis, causing faecoccal infections such as faecalis sepsis.

In patients with sepsis, there are fewer short-chain fatty acids in the intestine, which destroys the integrity of the intestinal epithelium, and the immune function is also impaired, and studies have shown that this short-chain fatty acid reduction can last at least 6 weeks.

Intestinal microecology and organ dysfunction

Sepsis can induce organ dysfunction through the disturbance of intestinal microecological structure.

Mouse experiments have shown that short-chain fatty acids produced by the intestinal microecology can reduce the risk of AKI. At the same time, some substances produced by the intestinal microecology can protect the liver.

Studies have also pointed out that the intestinal microecology can protect the center from delirium and other diseases. Compared with healthy people, ARDS patients have more intestinal flora in their lungs, which indicates that ARDS is associated with ectopic intestinal flora. But the specific cause and effect relationship needs to be further clarified by experiment.

Selective digestive tract decontamination and probiotics

Selective digestive decontamination refers to the use of antibiotics and other methods to eliminate pathogenic bacteria in the oral cavity and digestive tract, thereby reducing the risk of heterotopic intestinal flora. At present, this technology is not widely used and its effect is unknown. It is only used in some countries and has not been promoted. Further research is needed to confirm its effectiveness.

Probiotics are currently the most widely used technology to improve the intestinal microecology. An RCT experiment in 2017 included 4,500 newborn subjects, and finally found that probiotics can reduce the risk of neonatal sepsis and reduce mortality. But there are also studies on newborns that show that Lactobacillus probiotics will not improve the mortality rate and reduce the incidence of sepsis. The use of RNA technology has found that probiotics will not improve intestinal polymorphism, which has led to more and more doubts.

For critically ill patients, the results of studies on the efficacy of probiotics are also different. However, a meta-analysis found that probiotics can reduce the probability of infectious diseases and reduce the probability of VAP. Critically ill patients will use antibiotics, which may affect the efficacy of probiotics. The previous probiotics used bifidobacteria and lactic acid bacteria, and there are new types of probiotics that use other flora such as Akkermansia. Studies have found that it can improve the mortality of patients with sepsis. Related research is still in progress.

Fecal transplant

Probiotics can only contain a part of the intestinal flora, and intestinal fecal transplantation can contain many microorganisms, which can play a role in rebuilding the intestinal micro-ecology, which can theoretically improve the prognosis of sepsis from a variety of mechanisms .

There are currently 5 cases of fecal transplantation in the treatment of non-difficult Clostridium difficile sepsis. These medical records have their own characteristics, some are bacteremia, some are infections with multi-drug resistant bacteria, some are respiratory failure, and some are organ dysfunction. Before fecal transplantation, these patients had hemodynamic instability. After fecal transplantation, the fecal microbiota of these patients was similar to that of the donor. Four cases had a good prognosis and one case had an unclear result.

For patients with sepsis, the timing, effects, and operating standards of stool transplantation need to be further clarified. This technique may improve the prognosis of patients with sepsis in the future.

(source:internet, reference only)

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