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The intestinal tract is a main source of health-care associated pathogenic infections, not surprisingly due to the high concentration of microbes residing there.1 The GI tract is also considered to the primary reservoir for the emergence of antibiotic resistance of such infections.2 In patients with prolonged critical illness, the risk of developing a gut-derived sepsis (blood infection) is increased.

In a recent study published in the journal mBio, researchers analyzed the gut microbial composition of 14 critically ill patients under prolonged stay in an intensive care unit.3 They found ultra-low-diversity communities of bacteria consisting of only one to four species in 30 percent of the patients. This ultra-low diversity is the result of harsh conditions in the gut during critical illness, including multiple antibiotic exposure, reduced nutrition, physiological stress, and additional medications, some of which also affect gut microbes (acid-suppressors and opioids, in particular).

The most common bacteria in these patients detected by 16S rRNA sequencing were Enterococcus and Streptococcus as well as microbes under the family Enterobacteriaceae. Culture-based analyses also revealed the presence of Candida albicans and Candida glabrata in about 75 percent of the ICU patients. Four patients harbored a 2-member pathogen community consisting of one Candida and one bacterial organism.

“Here we demonstrate that the intestinal microbiome in critically ill patients can be considered a “damaged organ” given that its main cellular mass, the normal microbiota, is disrupted and dominated by pathobiota which may be an ever-threatening source for disseminating pathogens,” concluded the researchers.

In further experiments, the researchers determined that the ultra-low-diversity communities showed low virulence (pathogenicity) when they were grouped together, or living commensally as “friendly” organisms. The bacteria were able to keep the fungal Candida species in check, reducing their ability to become pathogenic. The researchers also tested the use of phosphate-polyethylene glycol (an anti-virulence compound) and found that it helped to reduce the pathogenicity of the microbes, suggesting that it might be a useful compound for critically ill patients with an ultra-low diversity of antibiotic-resistant gut microbes.

“A major challenge in treating critically ill patients is the overuse of antibiotics, a practice that is often unavoidable with patients exposed to multiple invasive procedures and extreme physiologic stress,” noted the researchers.

Further study of compounds that positively affect gut microbe composition in this vulnerable population is needed.

Many critically ill patients are now getting a slow, continuous drip of liquid food fortified with gut supportive supplements such as zinc, glutamine, arginine, vitamin C, omega-3s, and many more. These feedings are administered either via a thin nasogastric tube or an endoscopically placed gastric feeding tube.

I personally think it is high time that prebiotics and probiotics be added to the feeding tube line. Many of these tubes have an extra opening to administer meds. The prebiotics could be administered with the continuous liquid feedings and the probiotics be injected via side port, ideally between antibiotic dosages. This allows for maintenance of microbial diversity and repopulation of probiotic species that diminish with chronic stress, which allows pathogenic bacteria and fungi to multiply out of control.

It has been well documented that probiotics ingest prebiotic fibers, creating short-chain fatty acids (SCFAs) such as butyrate, acetate, and propionate. All three of these have been shown to bind to GPR43, and GPR41 receptors in the gut lining and on the surface of white blood cells. This action majorly helps to balance the immune system so that it can appropriately deal with pathogenic bacteria and fungi without overdoing it and leading to autoimmune disease.

This is only one action of SCFAs, and only one of many ways immunity is balanced when supported by good nutrition and beneficial bacteria such as Lactobacillus and Bifidobacteria, and fungi such as Saccharomyces boulardii, signaling through many different pathways. The optimum situation is to provide the nutrients, supplements, and probiotics that support our “damaged organ”—the gut lining and beneficial microbes.

This article provides a good picture of what happens when our normal microbiome, which normally consists of several hundred microbial species, is reduced to 2 to 4 pathogenic bacteria and fungi while everything else has been starved or killed by antimicrobials. It makes perfect sense to replenish that which has been lost, a practice that should be, and is slowly becoming, standard of care today.

References

  1. Alverdy JC and Chang EB, “The re-emerging role of the intestinal microflora in critical illness and inflammation: why the gut hypothesis of sepsis syndrome will not go away.” J Leukoc Biol. 2008 Mar;83(3):461-6.
  2. Salyers AA, Gupta A, and Wang Y, “Human intestinal bacteria as reservoirs for antibiotic resistance genes.” Trends Microbiol. 2004 Sep;12(9):412-6.
  3. Zaborin A, Smith D, Garfield K, et al., “Membership and behavior of ultra-low-diversity pathogen communities present in the gut of humans during prolonged critical illness.” mBio. 23 2014 Sep;5(5):e01361–14.